Back to resultsStudy to Assess the Efficacy and Safety of Rilonacept Treatment in Participants With Recurrent Pericarditis (RHAPSODY)
Primary Purpose
Recurrent Pericarditis
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Rilonacept
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Pericarditis
Eligibility Criteria
Key Inclusion Criteria:
- Male or female aged 12 or older
- Has a diagnosis of recurrent pericarditis
- Must provide Informed Consent
- Presents with at least the third episode of pericarditis during screening.
- Has received nonsteroidal anti-inflammatory drugs (NSAIDs) and/or colchicine and/or corticosteroids (in any combination), if used, at stable dose levels (or at least not increased) for at least 3 days prior to first study drug administration
- Female subjects must be postmenopausal, or incapable of pregnancy or permanently sterile, or if of childbearing potential must agree to use highly-effective method of contraception.
- Must be up-to-date with all immunizations, in agreement with current local immunization guidelines for immunosuppressed subjects, before first study drug administration.
- Is able to adequately maintain a daily subject diary according to protocol.
- Agrees to refrain from making any new, major lifestyle changes that may affect pericarditis symptoms (e.g., changing exercise pattern) from the time that the informed consent form (ICF) is signed through the end of the double-blind randomized withdrawal period.
Key Exclusion Criteria:
- Has a diagnosis of pericarditis that is secondary to specific prohibited etiologies.
- Has a history of immunosuppression, including positive human immunodeficiency virus (HIV) test results.
- Has a history of myeloproliferative disorder.
- Has a history of demyelinating disease or symptoms suggestive of multiple sclerosis.
- Has a history of active or latent tuberculosis (TB) prior to screening
- Has chest x-ray at screening or within 12 weeks before receiving first administration of study drug, with evidence of malignancy or abnormality consistent with prior or active TB infection.
- Has a history of positive or intermediate results for hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus antibody at screening.
- Has a history of malignancy of any organ system within the past 5 years before screening (other than a successfully treated non metastatic cutaneous squamous cell carcinoma or basal cell carcinoma and/or localized carcinoma in situ of the cervix).
- Has a known or suspected current active infection or a history of chronic or recurrent infectious disease, including, but not limited to, chronic renal infection, chronic chest infection, sinusitis, recurrent urinary tract infection, or an open, draining infected skin wound.
- Has had an organ transplant.
- In the Investigator's opinion, has a history of alcoholism or drug/chemical abuse within 2 years before screening.
- Has a known hypersensitivity to rilonacept or to any of its excipients.
- Has received an investigational drug during the 30 days before screening or is planning to receive an investigational drug (other than that administered during this study) or use an investigational device at any time during the study.
- In the Investigator's opinion, has any other medical condition that could adversely affect the subject's participation or interfere with study evaluations.
Sites / Locations
- Cedars-Sinai Medical Institute
- Arthritis and Rheumatology of Georgia
- The Loretto Hospital
- Minneapolis Heart Institute Foundation
- Mayo Clinic - PPDS
- Cincinnati Children's Hospital Medical Center
- Cleveland Clinic
- Cardiology Consultants of Philadelphia
- Intermountain Healthcare
- University Of Vermont Medical Center
- Virginia Commonwealth University
- Swedish Medical Center
- HeartCare Partners Clinical Research Unit
- GenesisCare - Cardiology Research
- Bnai Zion Medical Center
- Shaare Zedek Medical Center
- Galilee Medical Center
- Sheba Medical Center at Tel-Hashomer
- Ospedale Pediatrico Bambino Gesù
- ASST Fatebenefratelli Sacco - Ospedale Fatebenefratelli e Oftalmico
- Azienda Ospedaliera Città della Salute e della Scienza di Torino
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Rilonacept
Placebo
Arm Description
RI period: single-blind rilonacept 320 mg (or 4.4 mg/kg in pediatric participants) SC, followed by 160 mg (or 2.2 mg/kg in pediatric participants) injections once weekly. RW period: eligible participants randomized to double-blinded administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly. Participants with pericarditis recurrence who meet the protocol criteria for bailout rilonacept (report at least 1 day with pericarditis pain ≥4 on the 11-point NRS and have 1 CRP value ≥ 1 mg/dL [either on the same day or separated by no more than 7 days]) receive bailout rilonacept (2 open-label injections of 160 mg rilonacept [or 4.4 mg/kg for pediatric participants]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection. LTE period: open-label administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly.
RI period: single-blind rilonacept 320 mg (or 4.4 mg/kg in pediatric participants) SC, followed by 160 mg (or 2.2 mg/kg in pediatric participants) injections once weekly. RW period: eligible participants randomized to placebo SC injections once weekly. Participants with pericarditis recurrence who meet the protocol criteria for bailout rilonacept (report at least 1 day with pericarditis pain ≥4 on the 11-point NRS and have 1 CRP value ≥ 1 mg/dL [either on the same day or separated by no more than 7 days]) receive bailout rilonacept (2 open-label injections of 160 mg rilonacept [or 4.4 mg/kg for pediatric participants]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection. LTE period: open-label administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly.
Outcomes
Primary Outcome Measures
Time to Pericarditis Recurrence in the RW Period
Time to pericarditis recurrence (from randomization to 1st recurrence). Kaplan-Meier. Clinical Events Committee (CEC)-confirmed recurrences used for primary analysis. Recurrence defined as recurrence typical pericarditis pain with supportive objective evidence. CEC-adjudicated recurrences defined as:1) Re-appearance/worsening pericarditis pain (1 NRS ≥ 4) AND elevated CRP (≥1.0 mg/dL) on same day/separated by ≤ 7 days OR 2) Re-appearance/worsening pericarditis pain (1 NRS ≥ 4) AND abnormal CRP (> 0.5 mg/dL) on same day/separated by ≤ 7 days AND 1 supportive evidence OR 3) Re-appearance/worsening pericarditis pain (no NRS ≥ 4) AND elevated CRP (≥ 1.0 mg/dL) not attributable to other causes AND 1 supportive evidence. Supportive evidence: White blood cell count > upper limit normal, fever > 38C, pericardial rub, electrocardiogram changes consistent with pericarditis, new/worsening pericardial effusion (echocardiogram), new/worsening pericardial inflammation (magnetic resonance imaging).
Secondary Outcome Measures
Major Secondary Efficacy Endpoint: Percentage of Participants Who Maintained Clinical Response at Week 16 of the RW Period
Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Clinical response was defined as a weekly average of daily pericarditis pain on the NRS ≤ 2.0 and C-reactive protein (CRP) level ≤ 0.5 mg/dL, and on monotherapy of randomized study drug at Week 16.
Major Secondary Efficacy Endpoint: Percentage of Days With No or Minimal Pericarditis Pain at Week 16 of the RW Period
Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. No or minimal pain was defined as non-missing NRS ≤ 2.
The percentage of days with no or minimal pericarditis pain in the first 16 weeks was calculated for each participant using 16×7 as the denominator. Missing values in pain diary were counted as 0 day with no or minimal pain. Days of using oral rescue therapy or corticosteroid count as 0 day with no or minimal pain. If bailout rilonacept was used, each administration (loading dose or not) was counted as 7 days without qualifying no or minimal pain.
Major Secondary Efficacy Endpoint: Percentage of Participants With Absent or Minimal Pericarditis Symptoms Based on the Patient Global Impression of Pericarditis Severity (PGIPS) at Week 16 of the RW Period
Percentage of participants with no or minimal pericarditis symptoms at Week 16, based on the PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms that cannot be ignored and markedly limits daily activities).
The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Percentage of Participants Who Maintained Clinical Response at Week 24 of the RW Period
Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Clinical response was defined as a weekly average of daily pericarditis pain on the NRS ≤ 2.0 and C-reactive protein (CRP) level ≤ 0.5 mg/dL, and on monotherapy of randomized study drug at Week 24.
Percentage of Participants Who Maintained Clinical Response at Week 8 of the RW Period
Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Clinical response was defined as a weekly average of daily pericarditis pain on the NRS ≤ 2.0 and C-reactive protein (CRP) level ≤ 0.5 mg/dL, and on monotherapy of randomized study drug at Week 8.
Percentage of Days With No or Minimal Pericarditis Pain at Week 24 of the RW Period
Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. No or minimal pain was defined as non-missing NRS ≤ 2.
The percentage of days with no or minimal pericarditis pain in the first 24 weeks was calculated for each participant using 24×7 as the denominator. Missing values in pain diary were counted as 0 day with no or minimal pain. Days of using oral rescue therapy or corticosteroid count as 0 day with no or minimal pain. If bailout rilonacept was used, each administration (loading dose or not) was counted as 7 days without qualifying no or minimal pain.
Percentage of Days With No or Minimal Pericarditis Pain at Week 8 of the RW Period
Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. No or minimal pain was defined as non-missing NRS ≤ 2.
The percentage of days with no or minimal pericarditis pain in the first 24 weeks was calculated for each participant using 8×7 as the denominator. Missing values in pain diary were counted as 0 day with no or minimal pain. Days of using oral rescue therapy or corticosteroid count as 0 day with no or minimal pain. If bailout rilonacept was used, each administration (loading dose or not) was counted as 7 days without qualifying no or minimal pain.
Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 24 of the RW Period Based on the PGIPS
Percentage of participants with no or minimal pericarditis symptoms at Week 24, based on the PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms cannot be ignored and markedly limits daily activities).
The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 8 of the RW Period Based on the PGIPS
Percentage of participants with no or minimal pericarditis symptoms at Week 16, based on the Patient Global Impression of Pericarditis Severity (PGI-PS). The PGI-PS is a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered, using a 7-point rating scale ranging from absent (no recurrent pericarditis symptoms) to very severe (recurrent pericarditis symptoms cannot be ignored).
The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Percentage of Participants Without Pericarditis Recurrence in the First 24 Weeks of the RW Period
Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis. At any time during the RW period, participants who experienced a suspected recurrence of pericarditis symptoms reported to the study site/clinic for a scheduled or unscheduled visit, during which clinical assessments were performed to gather all the necessary diagnostic data to confirm or rule out the presence of pericarditis recurrence. A pericarditis recurrence event adjudication package was then prepared for adjudication by CEC. Kaplan-Meier estimate.
Time to Pericarditis Pain ≥ 4 on the NRS in the RW Period
Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'.
Time to CRP Level ≥ 1 mg/dL in the RW Period
Kaplan-Meier estimate.
Time to Pericardial Rub in the RW Period
Kaplan-Meier estimate. A pericardial rub (also called a pericardial friction rub) is an audible medical sign used in the diagnosis of pericarditis.
Time to Widespread ST-segment Elevation or PR-segment Depression on Electrocardiogram (ECG) in the RW Period
Kaplan-Meier estimate. ST-segment elevation and PR-segment depression are ECG changes in the evolution of acute pericarditis.
Time to New or Worsening Pericardial Effusion on Echocardiography (ECHO) in the RW Period
Pericardial effusion based on ECHO was evaluated by the central laboratory during the RW period. Kaplan-Meier estimate.
Number of Participants in ECHO Pericardial Effusion Size Categories at RW Period Baseline, RW Week 24 and Worst Post-baseline in the RW Period
Pericardial effusion based on ECHO was evaluated by the central laboratory during the RW period. "None or trivial/physiologic" is considered to be normal. The "RW Worst Post-baseline" category denotes the largest size of pericardial effusion category in which a participant was reported at any time during the RW period (post-baseline).
Change From RW Period Baseline Over Time in CRP Levels in RW Period
Estimated from ANCOVA models including treatment arm as fix effect, baseline value, baseline value by treatment interaction, randomization strata as covariates.
Change From RW Period Baseline Over Time in Weekly Average of Pericarditis Pain in the RW Period
Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Estimated from ANCOVA models including treatment arm as fix effect, baseline value, baseline value by treatment interaction, randomization strata as covariates.
Percentage of Participants With Absent or Minimal Pericarditis Symptoms Over Time After RW Period Week 24 Based on the PGIPS
The PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms cannot be ignored and markedly limits daily activities).
The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Percentage of Participants With Absent or Minimal Pericarditis Activity Over Time in the RW Period Based on the Physician Global Assessment of Pericarditis Activity (PGA-PA)
The PGA-PA is a single-item, clinician-reported outcome measure that Investigators use to rate their impression of the patient's overall pericarditis disease activity at the time the assessment is completed, using a rating scale ranging from absent to very severe. The Investigator selected the box that best described a participant's pericarditis activity at the time of occurrence of the assessment: Absent, Minimal, Mild, Moderate, Moderately Severe, Severe, Very Severe.
Change From RW Period Baseline in Short Form-36 (SF-36) Physical and Mental Component Scores at RW Period Week 24
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the physical component summary (PCS) score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best) with higher scores indicating better health. Increases from baseline indicate improvement.
Change From RW Baseline in SF-36 Individual Scores at RW Period Week 24
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item are summed and averaged (range: 0=worst to 100=best) with higher scores indicating better health. Increases from baseline indicate improvement.
Change From RW Period Baseline in the Short Form Health Survey-6 Domains (SF-6D) Utility Index Score at RW Period Week 24
The SF-6D is calculated based on responses to 11 items on the SF-36, that correspond to 6 domains: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. Individual respondents can be classified on any of 4 to 6 levels of functioning or limitations for each of 6 domains, thus allowing a respondent to be classified into any of 18,000 possible unique health states. Using a standard gamble technique, each of these health states were mapped onto the SF-6D index score, which ranges from 0.00 (worst possible health state/death) to 1.00 (best possible health state/perfect health).
Change From RW Period Baseline in 5-level EuroQoL-5 Dimensions (EQ-5D-5L) Individual Scores and Index Value to RW Period Week 24
The EQ-5D-5L is a self-reported health status questionnaire that consists of 6 questions used to calculate a health utility score for use in health economic analysis. There are 2 components to the EQ-5D-5L: a 5-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Individual and index scores range from 0 to 1, with low scores representing a higher level of dysfunction. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Change From RW Period Baseline in Insomnia Severity Index (ISI) Total Score at RW Period Week 24
Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.
Clinical interpretation of the total score is as follows:
0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Change in ISI Categories From RW Period Baseline to RW Period Week 24
Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.
Clinical interpretation of the total score is as follows:
0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Percentage of Participants Using Oral Rescue Therapy (ORT), Corticosteroid, or Bailout Rilonacept for Pericarditis Every 4 Weeks Cumulatively in the RW Period
ORT included analgesics, NSAIDs, and/or colchicine. ORT use while waiting for at least 5 days since previous administration of study drug before receiving bailout, or within 5 days before the assessment of pericarditis recurrence, was excluded.
Percentage of Participants Using ORT for Pericarditis in the First 24 Weeks of RW Period
ORT included analgesics, NSAIDs, and/or colchicine.
Percentage of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion on Magnetic Resonance Imaging (MRI) at RW Week 24
MRI assessments were performed in a subgroup of participants (MRI substudy) to assess the percentage of participants with:
Pericardial delayed hyperenhancement
Myocardial delayed hyperenhancement
Pericardial effusion
Time From First Dose to Pain Response in the RI Period
Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Time to pain response was defined as number of days from first dose to the first day a participant's daily pain NRS was ≤ 2 of the 3 days over which the rolling average daily pain NRS was ≤ 2.
Time From First Dose to CRP Normalization in the RI Period
Time to CRP normalization, defined as CRP ≤ 0.5 mg/dL, was censored at treatment discontinuation, taking prohibited medication, or Week 12, whichever occurred first.
Time From First Dose to Rilonacept Monotherapy in RI Period
Time to rilonacept monotherapy was defined as the number of weeks from first dose to the first day of achieving monotherapy.
Time From First Dose to Treatment Response in RI Period
Time to treatment response is defined as time from first dose to the first day of pain response, and CRP ≤ 0.5 mg/dL within 7 days before or after pain response. Treatment response day will be the first day that the above criterion is met. If pain response occurs before CRP ≤ 0.5 mg/dL, each 3-day rolling average of NRS should be ≤ 2.0 from the day of pain response to the day of CRP ≤ 0.5 mg/dL. The response day will be the day of pain response. If CRP ≤0.5 mg/dL occurs before pain response, the response day will also be the day of pain response.
Percentage of Participants Achieving Clinical Response at RI Period Week 12
Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Clinical Response was defined as a weekly average of daily pericarditis pain of ≤ 2.0 on the 11-point NRS and CRP level ≤ 0.5 mg/dL and participants must have been able to stop background SOC pericarditis therapy by Week 10.
Percentage of Participants With CRP Normalization at RI Period Week 12
CRP normalization was defined as CRP ≤ 0.5 mg/dL.
Change From Baseline Over Time in Weekly Average of Pericarditis Pain NRS Score in RI Period
Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'.
Change From Baseline Over Time in CRP Levels in RI Period
Percentage of Participants With Resolution of Pericarditis-Related ECHO and ECG Abnormalities at Week 12 of the RI Period
Percentage of Days With No or Minimal Pain in the RI Period While on Treatment
No or minimal pain is defined as non-missing daily NRS ≤ 2, where participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point NRS, where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'.
Percentage of Participants With No or Minimal Pericarditis Symptoms Over Time in the RI Period, Based on the PGIPS
The PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms cannot be ignored and markedly limits daily activities).
The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Percentage of Participants With No or Minimal Pericarditis Activity Over Time in the RI Period, Based on the PGA-PA
The PGA-PA is a single-item, clinician-reported outcome measure that Investigators use to rate their impression of the patient's overall pericarditis disease activity at the time the assessment is completed, using a rating scale ranging from absent to very severe. The Investigator selected the box that best described a participant's pericarditis activity at the time of occurrence of the assessment: Absent, Minimal, Mild, Moderate, Moderately Severe, Severe, Very Severe.
The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Change From RI Period Baseline in the SF-36 Domain Scores and Physical and Mental Scores to RI Period Week 12
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item are summed and averaged (range: 0=worst to 100=best) with higher scores indicating better health. Increases from baseline indicate improvement.
Change From RI Period Baseline in SF-6D Scores at RI Period Week 12
The SF-6D is calculated based on responses to 11 items on the SF-36, that correspond to 6 domains: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. Individual respondents can be classified on any of 4 to 6 levels of functioning or limitations for each of 6 domains, thus allowing a respondent to be classified into any of 18,000 possible unique health states. Using a standard gamble technique, each of these health states were mapped onto the SF-6D index score, which ranges from 0.00 (worst possible health state/death) to 1.00 (best possible health state/perfect health).
Change From RI Period Baseline in 5-level EuroQoL-5 Dimensions (EQ-5D-5L) Individual Scores and Index Value at RI Period Week 12
The EQ-5D-5L is a self-reported health status questionnaire that consists of 6 questions used to calculate a health utility score for use in health economic analysis. There are 2 components to the EQ-5D-5L: a 5-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Individual and index scores range from 0 to 1, with low scores representing a higher level of dysfunction. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Change From RI Period Baseline in ISI Total Score at RI Period Week 12
Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.
Clinical interpretation of the total score is as follows:
0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Change in ISI Categories From RI Period Baseline to RI Period Week 12
Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.
Clinical interpretation of the total score is as follows:
0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Number of Participants Who Were Off Background Pericarditis Medication on or Before RI Period Weeks 4, 8, 10, and 12
Annualized Rate of Pericarditis Recurrence in the Long-Term Extension (LTE) Period Based on Investigator's Assessment (Based on Investigators' Judgement)
Annualized Recurrence Rate is defined as the number of recurrences in LTE periods for all participants/Sum of participant years in LTE periods for all participants. Participant years in LTE period is defined as the time from 1st dose date of LTE period to the date of End of Study, or data cutoff date, whichever is earlier. The 95% CI was calculated using an exact method with Poisson distribution. Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis.
Change From LTE Baseline Over Time in CRP Levels
Percentage of Participants With Absent or Minimal Pericarditis Activity In the LTE Period Based on the PGIPS
Percentage of participants with no or minimal pericarditis symptoms in the LTE Period, based on the PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms that cannot be ignored and markedly limits daily activities).
Percentage of Participants With Absent or Minimal Pericarditis Activity Over Time in the LTE Period Based on the PGA-PA
The PGA-PA is a single-item, clinician-reported outcome measure that Investigators use to rate their impression of the patient's overall pericarditis disease activity at the time the assessment is completed, using a rating scale ranging from absent to very severe. The Investigator selected the box that best described a participant's pericarditis activity at the time of occurrence of the assessment: Absent, Minimal, Mild, Moderate, Moderately Severe, Severe, Very Severe.
Change From LTE Baseline in the SF-36 Domain Scores and Physical and Mental Scores
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item are summed and averaged (range: 0=worst to 100=best) with higher scores indicating better health. Increases from baseline indicate improvement.
Change From LTE Baseline in SF-6D Health Utility Index Score
The SF-6D is calculated based on responses to 11 items on the SF-36, that correspond to 6 domains: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. Individual respondents can be classified on any of 4 to 6 levels of functioning or limitations for each of six domains, thus allowing a respondent to be classified into any of 18,000 possible unique health states. Using a standard gamble technique, each of these health states were mapped onto the SF-6D index score, which ranges from 0.00 (worst possible health state/death) to 1.00 (best possible health state/perfect health).
Change From LTE Baseline in EQ-5D-5L Individual Scores and Index Value
The EQ-5D-5L is a self-reported health status questionnaire that consists of 6 questions used to calculate a health utility score for use in health economic analysis. There are 2 components to the EQ-5D-5L: a 5-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Individual and index scores range from 0 to 1, with low scores representing a higher level of dysfunction. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Change From LTE Baseline in ISI Total Score
Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.
Clinical interpretation of the total score is as follows:
0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Change From LTE Baseline in ISI Categories
Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.
Clinical interpretation of the total score is as follows:
0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Percentage of Participants Requiring Addition of Standard of Care (SOC) Pericarditis Therapy Every 4 Weeks Cumulatively in the LTE Period
Change From LTE Baseline in Pericardial Signs in ECHO
Change From LTE Baseline in Pericardial Signs in ECG
Change From LTE Baseline in Pericardial Signs in MRI
Number of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion at LTE Period Week 24
Annualized Rate of Pericarditis Recurrence in LTE Periods Based on Investigator's Assessment
Annualized Recurrence Rate is defined as number of recurrences in LTE periods for all participants/Sum of participant years in LTE period for all participants. Participant years in LTE period is defined as the time from 1st dose date of LTE period to the date of End of Study, or data cutoff date, whichever is earlier. The 95% CI was calculated using an exact method with Poisson distribution.
Pericarditis recurrence was defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis. At any time during the RW period, participants who experienced a suspected recurrence of pericarditis symptoms reported to the study site/clinic for a scheduled or unscheduled visit, during which clinical assessments were performed to gather all the necessary diagnostic data to confirm or rule out the presence of pericarditis recurrence.
Annualized Rate of Pericarditis Recurrence in RW Period Based on CEC Adjudication
Annualized Recurrence Rate is defined as the number of recurrences in RW period for all participants/Sum of participant years in RW period for all participants. Participant years in RW period is defined as the time from randomization date to the date of EORW or last dose date + 6 weeks, whichever is earlier. The 95% CI was calculated using an exact method with Poisson distribution.
Pericarditis recurrence was defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis. At any time during the RW period, participants who experienced a suspected recurrence of pericarditis symptoms reported to the study site/clinic for a scheduled or unscheduled visit, during which clinical assessments were performed to gather all the necessary diagnostic data to confirm or rule out the presence of pericarditis recurrence.
Full Information
NCT ID
NCT03737110
First Posted
October 30, 2018
Last Updated
August 14, 2023
Sponsor
Kiniksa Pharmaceuticals (UK), Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03737110
Brief Title
Study to Assess the Efficacy and Safety of Rilonacept Treatment in Participants With Recurrent Pericarditis
Acronym
RHAPSODY
Official Title
Phase 3, Double-Blind, Placebo-Controlled, Randomized Withdrawal Study With Open-label Extension, to Assess the Efficacy and Safety of Rilonacept Treatment in Subjects With Recurrent Pericarditis
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
January 7, 2019 (Actual)
Primary Completion Date
May 29, 2020 (Actual)
Study Completion Date
June 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kiniksa Pharmaceuticals (UK), Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective of this study was to assess the efficacy of rilonacept treatment in participants with recurrent pericarditis.
Detailed Description
In the single-blind run-in (RI) period, rilonacept 320 mg (or 4.4 mg/kg in pediatric participants ≥12 and <18 years old) subcutaneous (SC), followed by 160 mg (or 2.2 mg/kg in pediatric participants ≥12 and <18 years old) injections once weekly.
During the Randomized-Withdrawal (RW) period, eligible participants are randomized 1:1 to double-blinded administration of study drug:
Rilonacept 160 mg (or 2.2 mg/kg in pediatric participants ≥12 and <18 years old) SC injections once weekly
Matching placebo SC injections once weekly.
Participants with pericarditis recurrence who meet the protocol criteria for bailout rilonacept (report at least 1 day with pericarditis pain ≥4 on the 11-point numerical rating scale (NRS) and have 1 C-reactive protein (CRP) value ≥ 1 mg/dL [either on the same day or separated by no more than 7 days]) receive bailout rilonacept (2 open-label injections of 160 mg rilonacept [or 4.4 mg/kg for pediatric subjects]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection.
Upon completion of the RW period (i.e., when the prespecified number of primary efficacy endpoints [clinical events committee-confirmed pericarditis recurrence] events have occurred), all participants who did not discontinue study drug have an option to continue treatment with open-label rilonacept in the Long-Term Extension (LTE) or to withdraw from the study. Participants still in the RI period at the time that the RW period has ended and the LTE is opened will have the option to enter the LTE directly when they have completed the RI period and have met the definition of clinical response or to withdraw from the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Pericarditis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
86 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rilonacept
Arm Type
Experimental
Arm Description
RI period: single-blind rilonacept 320 mg (or 4.4 mg/kg in pediatric participants) SC, followed by 160 mg (or 2.2 mg/kg in pediatric participants) injections once weekly.
RW period: eligible participants randomized to double-blinded administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly. Participants with pericarditis recurrence who meet the protocol criteria for bailout rilonacept (report at least 1 day with pericarditis pain ≥4 on the 11-point NRS and have 1 CRP value ≥ 1 mg/dL [either on the same day or separated by no more than 7 days]) receive bailout rilonacept (2 open-label injections of 160 mg rilonacept [or 4.4 mg/kg for pediatric participants]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection.
LTE period: open-label administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
RI period: single-blind rilonacept 320 mg (or 4.4 mg/kg in pediatric participants) SC, followed by 160 mg (or 2.2 mg/kg in pediatric participants) injections once weekly.
RW period: eligible participants randomized to placebo SC injections once weekly. Participants with pericarditis recurrence who meet the protocol criteria for bailout rilonacept (report at least 1 day with pericarditis pain ≥4 on the 11-point NRS and have 1 CRP value ≥ 1 mg/dL [either on the same day or separated by no more than 7 days]) receive bailout rilonacept (2 open-label injections of 160 mg rilonacept [or 4.4 mg/kg for pediatric participants]) irrespective of randomized treatment assignment and as soon as at least 5 days have passed since the last study drug injection.
LTE period: open-label administration of rilonacept 160 mg (or 2.2 mg/kg in pediatric participants) SC injections once weekly.
Intervention Type
Drug
Intervention Name(s)
Rilonacept
Other Intervention Name(s)
KPL-914, Arcalyst® for Cryopyrin-Associated Periodic Syndromes (CAPS)
Intervention Description
Rilonacept 320 mg (or 4.4 mg/kg in pediatric participants ≥12 and <18 years old) SC , followed by 160 mg (or 2.2 mg/kg in pediatric participants ≥12 and <18 years old) injections once weekly
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo SC injections once weekly
Primary Outcome Measure Information:
Title
Time to Pericarditis Recurrence in the RW Period
Description
Time to pericarditis recurrence (from randomization to 1st recurrence). Kaplan-Meier. Clinical Events Committee (CEC)-confirmed recurrences used for primary analysis. Recurrence defined as recurrence typical pericarditis pain with supportive objective evidence. CEC-adjudicated recurrences defined as:1) Re-appearance/worsening pericarditis pain (1 NRS ≥ 4) AND elevated CRP (≥1.0 mg/dL) on same day/separated by ≤ 7 days OR 2) Re-appearance/worsening pericarditis pain (1 NRS ≥ 4) AND abnormal CRP (> 0.5 mg/dL) on same day/separated by ≤ 7 days AND 1 supportive evidence OR 3) Re-appearance/worsening pericarditis pain (no NRS ≥ 4) AND elevated CRP (≥ 1.0 mg/dL) not attributable to other causes AND 1 supportive evidence. Supportive evidence: White blood cell count > upper limit normal, fever > 38C, pericardial rub, electrocardiogram changes consistent with pericarditis, new/worsening pericardial effusion (echocardiogram), new/worsening pericardial inflammation (magnetic resonance imaging).
Time Frame
RW Period (mean 24.8 weeks)
Secondary Outcome Measure Information:
Title
Major Secondary Efficacy Endpoint: Percentage of Participants Who Maintained Clinical Response at Week 16 of the RW Period
Description
Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Clinical response was defined as a weekly average of daily pericarditis pain on the NRS ≤ 2.0 and C-reactive protein (CRP) level ≤ 0.5 mg/dL, and on monotherapy of randomized study drug at Week 16.
Time Frame
RW Period Week 16
Title
Major Secondary Efficacy Endpoint: Percentage of Days With No or Minimal Pericarditis Pain at Week 16 of the RW Period
Description
Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. No or minimal pain was defined as non-missing NRS ≤ 2.
The percentage of days with no or minimal pericarditis pain in the first 16 weeks was calculated for each participant using 16×7 as the denominator. Missing values in pain diary were counted as 0 day with no or minimal pain. Days of using oral rescue therapy or corticosteroid count as 0 day with no or minimal pain. If bailout rilonacept was used, each administration (loading dose or not) was counted as 7 days without qualifying no or minimal pain.
Time Frame
RW Period Week 16
Title
Major Secondary Efficacy Endpoint: Percentage of Participants With Absent or Minimal Pericarditis Symptoms Based on the Patient Global Impression of Pericarditis Severity (PGIPS) at Week 16 of the RW Period
Description
Percentage of participants with no or minimal pericarditis symptoms at Week 16, based on the PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms that cannot be ignored and markedly limits daily activities).
The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Time Frame
RW Period Week 16
Title
Percentage of Participants Who Maintained Clinical Response at Week 24 of the RW Period
Description
Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Clinical response was defined as a weekly average of daily pericarditis pain on the NRS ≤ 2.0 and C-reactive protein (CRP) level ≤ 0.5 mg/dL, and on monotherapy of randomized study drug at Week 24.
Time Frame
RW Period Week 24
Title
Percentage of Participants Who Maintained Clinical Response at Week 8 of the RW Period
Description
Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Clinical response was defined as a weekly average of daily pericarditis pain on the NRS ≤ 2.0 and C-reactive protein (CRP) level ≤ 0.5 mg/dL, and on monotherapy of randomized study drug at Week 8.
Time Frame
RW Period Week 8
Title
Percentage of Days With No or Minimal Pericarditis Pain at Week 24 of the RW Period
Description
Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. No or minimal pain was defined as non-missing NRS ≤ 2.
The percentage of days with no or minimal pericarditis pain in the first 24 weeks was calculated for each participant using 24×7 as the denominator. Missing values in pain diary were counted as 0 day with no or minimal pain. Days of using oral rescue therapy or corticosteroid count as 0 day with no or minimal pain. If bailout rilonacept was used, each administration (loading dose or not) was counted as 7 days without qualifying no or minimal pain.
Time Frame
RW Period Week 24
Title
Percentage of Days With No or Minimal Pericarditis Pain at Week 8 of the RW Period
Description
Participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. No or minimal pain was defined as non-missing NRS ≤ 2.
The percentage of days with no or minimal pericarditis pain in the first 24 weeks was calculated for each participant using 8×7 as the denominator. Missing values in pain diary were counted as 0 day with no or minimal pain. Days of using oral rescue therapy or corticosteroid count as 0 day with no or minimal pain. If bailout rilonacept was used, each administration (loading dose or not) was counted as 7 days without qualifying no or minimal pain.
Time Frame
RW Period Week 8
Title
Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 24 of the RW Period Based on the PGIPS
Description
Percentage of participants with no or minimal pericarditis symptoms at Week 24, based on the PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms cannot be ignored and markedly limits daily activities).
The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Time Frame
RW Period Week 24
Title
Percentage of Participants With Absent or Minimal Pericarditis Symptoms at Week 8 of the RW Period Based on the PGIPS
Description
Percentage of participants with no or minimal pericarditis symptoms at Week 16, based on the Patient Global Impression of Pericarditis Severity (PGI-PS). The PGI-PS is a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered, using a 7-point rating scale ranging from absent (no recurrent pericarditis symptoms) to very severe (recurrent pericarditis symptoms cannot be ignored).
The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Time Frame
RW Period Week 8
Title
Percentage of Participants Without Pericarditis Recurrence in the First 24 Weeks of the RW Period
Description
Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis. At any time during the RW period, participants who experienced a suspected recurrence of pericarditis symptoms reported to the study site/clinic for a scheduled or unscheduled visit, during which clinical assessments were performed to gather all the necessary diagnostic data to confirm or rule out the presence of pericarditis recurrence. A pericarditis recurrence event adjudication package was then prepared for adjudication by CEC. Kaplan-Meier estimate.
Time Frame
up to 24 weeks in the RW Period
Title
Time to Pericarditis Pain ≥ 4 on the NRS in the RW Period
Description
Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'.
Time Frame
RW Period (mean 24.8 weeks)
Title
Time to CRP Level ≥ 1 mg/dL in the RW Period
Description
Kaplan-Meier estimate.
Time Frame
RW Period (mean 24.8 weeks)
Title
Time to Pericardial Rub in the RW Period
Description
Kaplan-Meier estimate. A pericardial rub (also called a pericardial friction rub) is an audible medical sign used in the diagnosis of pericarditis.
Time Frame
RW Period (mean 24.8 weeks)
Title
Time to Widespread ST-segment Elevation or PR-segment Depression on Electrocardiogram (ECG) in the RW Period
Description
Kaplan-Meier estimate. ST-segment elevation and PR-segment depression are ECG changes in the evolution of acute pericarditis.
Time Frame
RW Period (mean 24.8 weeks)
Title
Time to New or Worsening Pericardial Effusion on Echocardiography (ECHO) in the RW Period
Description
Pericardial effusion based on ECHO was evaluated by the central laboratory during the RW period. Kaplan-Meier estimate.
Time Frame
RW Period (mean 24.8 weeks)
Title
Number of Participants in ECHO Pericardial Effusion Size Categories at RW Period Baseline, RW Week 24 and Worst Post-baseline in the RW Period
Description
Pericardial effusion based on ECHO was evaluated by the central laboratory during the RW period. "None or trivial/physiologic" is considered to be normal. The "RW Worst Post-baseline" category denotes the largest size of pericardial effusion category in which a participant was reported at any time during the RW period (post-baseline).
Time Frame
RW Period Baseline, RW Period Week 24, RW Period (mean 24.8 weeks)
Title
Change From RW Period Baseline Over Time in CRP Levels in RW Period
Description
Estimated from ANCOVA models including treatment arm as fix effect, baseline value, baseline value by treatment interaction, randomization strata as covariates.
Time Frame
RW Period Baseline, RW Period Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 56
Title
Change From RW Period Baseline Over Time in Weekly Average of Pericarditis Pain in the RW Period
Description
Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Estimated from ANCOVA models including treatment arm as fix effect, baseline value, baseline value by treatment interaction, randomization strata as covariates.
Time Frame
RW Period Baseline, RW Period Weeks 1-50, 54
Title
Percentage of Participants With Absent or Minimal Pericarditis Symptoms Over Time After RW Period Week 24 Based on the PGIPS
Description
The PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms cannot be ignored and markedly limits daily activities).
The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Time Frame
RW Period Weeks 32, 40, 48, 56
Title
Percentage of Participants With Absent or Minimal Pericarditis Activity Over Time in the RW Period Based on the Physician Global Assessment of Pericarditis Activity (PGA-PA)
Description
The PGA-PA is a single-item, clinician-reported outcome measure that Investigators use to rate their impression of the patient's overall pericarditis disease activity at the time the assessment is completed, using a rating scale ranging from absent to very severe. The Investigator selected the box that best described a participant's pericarditis activity at the time of occurrence of the assessment: Absent, Minimal, Mild, Moderate, Moderately Severe, Severe, Very Severe.
Time Frame
RW Period Baseline, RW Period Weeks 8, 16, 24, 32, 40, 48, 56
Title
Change From RW Period Baseline in Short Form-36 (SF-36) Physical and Mental Component Scores at RW Period Week 24
Description
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the physical component summary (PCS) score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best) with higher scores indicating better health. Increases from baseline indicate improvement.
Time Frame
RW Period Baseline, RW Period Week 24
Title
Change From RW Baseline in SF-36 Individual Scores at RW Period Week 24
Description
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item are summed and averaged (range: 0=worst to 100=best) with higher scores indicating better health. Increases from baseline indicate improvement.
Time Frame
RW Period Baseline, RW Period Week 24
Title
Change From RW Period Baseline in the Short Form Health Survey-6 Domains (SF-6D) Utility Index Score at RW Period Week 24
Description
The SF-6D is calculated based on responses to 11 items on the SF-36, that correspond to 6 domains: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. Individual respondents can be classified on any of 4 to 6 levels of functioning or limitations for each of 6 domains, thus allowing a respondent to be classified into any of 18,000 possible unique health states. Using a standard gamble technique, each of these health states were mapped onto the SF-6D index score, which ranges from 0.00 (worst possible health state/death) to 1.00 (best possible health state/perfect health).
Time Frame
RW Period Baseline, RW Period Week 24
Title
Change From RW Period Baseline in 5-level EuroQoL-5 Dimensions (EQ-5D-5L) Individual Scores and Index Value to RW Period Week 24
Description
The EQ-5D-5L is a self-reported health status questionnaire that consists of 6 questions used to calculate a health utility score for use in health economic analysis. There are 2 components to the EQ-5D-5L: a 5-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Individual and index scores range from 0 to 1, with low scores representing a higher level of dysfunction. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Time Frame
RW Period Baseline, RW Period Week 24
Title
Change From RW Period Baseline in Insomnia Severity Index (ISI) Total Score at RW Period Week 24
Description
Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.
Clinical interpretation of the total score is as follows:
0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Time Frame
RW Period Baseline, RW Period Week 24
Title
Change in ISI Categories From RW Period Baseline to RW Period Week 24
Description
Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.
Clinical interpretation of the total score is as follows:
0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Time Frame
RW Period Baseline (BL), RW Period Week (Wk) 24
Title
Percentage of Participants Using Oral Rescue Therapy (ORT), Corticosteroid, or Bailout Rilonacept for Pericarditis Every 4 Weeks Cumulatively in the RW Period
Description
ORT included analgesics, NSAIDs, and/or colchicine. ORT use while waiting for at least 5 days since previous administration of study drug before receiving bailout, or within 5 days before the assessment of pericarditis recurrence, was excluded.
Time Frame
RW Period (mean 24.8 weeks)
Title
Percentage of Participants Using ORT for Pericarditis in the First 24 Weeks of RW Period
Description
ORT included analgesics, NSAIDs, and/or colchicine.
Time Frame
RW Period (up to Week 24)
Title
Percentage of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion on Magnetic Resonance Imaging (MRI) at RW Week 24
Description
MRI assessments were performed in a subgroup of participants (MRI substudy) to assess the percentage of participants with:
Pericardial delayed hyperenhancement
Myocardial delayed hyperenhancement
Pericardial effusion
Time Frame
RW Period Week 24
Title
Time From First Dose to Pain Response in the RI Period
Description
Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Time to pain response was defined as number of days from first dose to the first day a participant's daily pain NRS was ≤ 2 of the 3 days over which the rolling average daily pain NRS was ≤ 2.
Time Frame
RI Period (up to 12 weeks)
Title
Time From First Dose to CRP Normalization in the RI Period
Description
Time to CRP normalization, defined as CRP ≤ 0.5 mg/dL, was censored at treatment discontinuation, taking prohibited medication, or Week 12, whichever occurred first.
Time Frame
RI Period (up to 12 weeks)
Title
Time From First Dose to Rilonacept Monotherapy in RI Period
Description
Time to rilonacept monotherapy was defined as the number of weeks from first dose to the first day of achieving monotherapy.
Time Frame
RI Period (up to 12 weeks)
Title
Time From First Dose to Treatment Response in RI Period
Description
Time to treatment response is defined as time from first dose to the first day of pain response, and CRP ≤ 0.5 mg/dL within 7 days before or after pain response. Treatment response day will be the first day that the above criterion is met. If pain response occurs before CRP ≤ 0.5 mg/dL, each 3-day rolling average of NRS should be ≤ 2.0 from the day of pain response to the day of CRP ≤ 0.5 mg/dL. The response day will be the day of pain response. If CRP ≤0.5 mg/dL occurs before pain response, the response day will also be the day of pain response.
Time Frame
RI Period (up to 12 weeks)
Title
Percentage of Participants Achieving Clinical Response at RI Period Week 12
Description
Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'. Clinical Response was defined as a weekly average of daily pericarditis pain of ≤ 2.0 on the 11-point NRS and CRP level ≤ 0.5 mg/dL and participants must have been able to stop background SOC pericarditis therapy by Week 10.
Time Frame
RI Period Week 12
Title
Percentage of Participants With CRP Normalization at RI Period Week 12
Description
CRP normalization was defined as CRP ≤ 0.5 mg/dL.
Time Frame
RI Period Week 12
Title
Change From Baseline Over Time in Weekly Average of Pericarditis Pain NRS Score in RI Period
Description
Participants were asked to select the score that best described their average level of pericarditis pain over the previous 24 hours using an 11-point numerical rating scale (NRS), where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'.
Time Frame
RI Period Baseline, RI Period Weeks 1-12
Title
Change From Baseline Over Time in CRP Levels in RI Period
Time Frame
RI Period Baseline, RI Period Day 4, Weeks 1, 2, 4, 6, 12
Title
Percentage of Participants With Resolution of Pericarditis-Related ECHO and ECG Abnormalities at Week 12 of the RI Period
Time Frame
RI Period Baseline, RI Period Week 12
Title
Percentage of Days With No or Minimal Pain in the RI Period While on Treatment
Description
No or minimal pain is defined as non-missing daily NRS ≤ 2, where participants were asked to select the score that best describes their average level of pericarditis pain over the previous 24 hours using an 11-point NRS, where zero (0) indicates 'no pain' and ten (10) indicates 'pain as bad as it could be'.
Time Frame
RI Period (up to Week 12)
Title
Percentage of Participants With No or Minimal Pericarditis Symptoms Over Time in the RI Period, Based on the PGIPS
Description
The PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms cannot be ignored and markedly limits daily activities).
The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Time Frame
RI Period Baseline, RI Period Weeks 6 and 12
Title
Percentage of Participants With No or Minimal Pericarditis Activity Over Time in the RI Period, Based on the PGA-PA
Description
The PGA-PA is a single-item, clinician-reported outcome measure that Investigators use to rate their impression of the patient's overall pericarditis disease activity at the time the assessment is completed, using a rating scale ranging from absent to very severe. The Investigator selected the box that best described a participant's pericarditis activity at the time of occurrence of the assessment: Absent, Minimal, Mild, Moderate, Moderately Severe, Severe, Very Severe.
The exact 95% CI is calculated with randomization strata pooled. Participants who had received bailout rilonacept or rescue medication before the time point were considered nonresponders.
Time Frame
RI Period Baseline, RI Period Weeks 6 and 12
Title
Change From RI Period Baseline in the SF-36 Domain Scores and Physical and Mental Scores to RI Period Week 12
Description
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item are summed and averaged (range: 0=worst to 100=best) with higher scores indicating better health. Increases from baseline indicate improvement.
Time Frame
RI Period Baseline, RI Period Week 12
Title
Change From RI Period Baseline in SF-6D Scores at RI Period Week 12
Description
The SF-6D is calculated based on responses to 11 items on the SF-36, that correspond to 6 domains: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. Individual respondents can be classified on any of 4 to 6 levels of functioning or limitations for each of 6 domains, thus allowing a respondent to be classified into any of 18,000 possible unique health states. Using a standard gamble technique, each of these health states were mapped onto the SF-6D index score, which ranges from 0.00 (worst possible health state/death) to 1.00 (best possible health state/perfect health).
Time Frame
RI Period Baseline, RI Period Week 12
Title
Change From RI Period Baseline in 5-level EuroQoL-5 Dimensions (EQ-5D-5L) Individual Scores and Index Value at RI Period Week 12
Description
The EQ-5D-5L is a self-reported health status questionnaire that consists of 6 questions used to calculate a health utility score for use in health economic analysis. There are 2 components to the EQ-5D-5L: a 5-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Individual and index scores range from 0 to 1, with low scores representing a higher level of dysfunction. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Time Frame
RI Period Baseline, RI Period Week 12
Title
Change From RI Period Baseline in ISI Total Score at RI Period Week 12
Description
Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.
Clinical interpretation of the total score is as follows:
0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Time Frame
RI Period Baseline, RI Period Week 12
Title
Change in ISI Categories From RI Period Baseline to RI Period Week 12
Description
Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.
Clinical interpretation of the total score is as follows:
0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Time Frame
RI Period Baseline (BL), RI Period Week (Wk) 12
Title
Number of Participants Who Were Off Background Pericarditis Medication on or Before RI Period Weeks 4, 8, 10, and 12
Time Frame
RI Period Baseline, RI Period Weeks 4, 8, 10, 12
Title
Annualized Rate of Pericarditis Recurrence in the Long-Term Extension (LTE) Period Based on Investigator's Assessment (Based on Investigators' Judgement)
Description
Annualized Recurrence Rate is defined as the number of recurrences in LTE periods for all participants/Sum of participant years in LTE periods for all participants. Participant years in LTE period is defined as the time from 1st dose date of LTE period to the date of End of Study, or data cutoff date, whichever is earlier. The 95% CI was calculated using an exact method with Poisson distribution. Pericarditis recurrence is defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis.
Time Frame
LTE Period, through LTE Follow up (up to Week 48)
Title
Change From LTE Baseline Over Time in CRP Levels
Time Frame
LTE Baseline, LTE Week 12, LTE Week 24
Title
Percentage of Participants With Absent or Minimal Pericarditis Activity In the LTE Period Based on the PGIPS
Description
Percentage of participants with no or minimal pericarditis symptoms in the LTE Period, based on the PGIPS, a single-item measure of the participant's impression of the overall severity of pericarditis symptoms at the time the questionnaire is administered using a 7-point rating scale ranging from absent (0=no recurrent pericarditis symptoms) to very severe (6=recurrent pericarditis symptoms that cannot be ignored and markedly limits daily activities).
Time Frame
LTE Baseline, LTE Month 12, LTE Month 24
Title
Percentage of Participants With Absent or Minimal Pericarditis Activity Over Time in the LTE Period Based on the PGA-PA
Description
The PGA-PA is a single-item, clinician-reported outcome measure that Investigators use to rate their impression of the patient's overall pericarditis disease activity at the time the assessment is completed, using a rating scale ranging from absent to very severe. The Investigator selected the box that best described a participant's pericarditis activity at the time of occurrence of the assessment: Absent, Minimal, Mild, Moderate, Moderately Severe, Severe, Very Severe.
Time Frame
LTE Baseline, LTE Week 12, LTE Week 24
Title
Change From LTE Baseline in the SF-36 Domain Scores and Physical and Mental Scores
Description
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item are summed and averaged (range: 0=worst to 100=best) with higher scores indicating better health. Increases from baseline indicate improvement.
Time Frame
LTE Baseline, LTE Week 24
Title
Change From LTE Baseline in SF-6D Health Utility Index Score
Description
The SF-6D is calculated based on responses to 11 items on the SF-36, that correspond to 6 domains: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. Individual respondents can be classified on any of 4 to 6 levels of functioning or limitations for each of six domains, thus allowing a respondent to be classified into any of 18,000 possible unique health states. Using a standard gamble technique, each of these health states were mapped onto the SF-6D index score, which ranges from 0.00 (worst possible health state/death) to 1.00 (best possible health state/perfect health).
Time Frame
LTE Baseline, LTE Week 24
Title
Change From LTE Baseline in EQ-5D-5L Individual Scores and Index Value
Description
The EQ-5D-5L is a self-reported health status questionnaire that consists of 6 questions used to calculate a health utility score for use in health economic analysis. There are 2 components to the EQ-5D-5L: a 5-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used to obtain an Index Utility Score, as well as a visual analogue scale (VAS) that measures health state. Individual and index scores range from 0 to 1, with low scores representing a higher level of dysfunction. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Time Frame
LTE Baseline, LTE Week 24
Title
Change From LTE Baseline in ISI Total Score
Description
Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.
Clinical interpretation of the total score is as follows:
0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Time Frame
LTE Baseline, LTE Week 24
Title
Change From LTE Baseline in ISI Categories
Description
Participant's sleep quality was assessed with the ISI survey questionnaire. The ISI is a 7-item survey, with each question having 5 possible answers (none, mild, moderate, severe, or very severe), scored as 0, 1, 2, 3, or 4, respectively. Scores are summed for a total score, which ranges from 0 to 28. Lower scores are considered good, better, or healthy, and increasingly higher scores are considered to indicate greater insomnia.
Clinical interpretation of the total score is as follows:
0 to 7 = no clinically significant insomnia; 8 to 14 = subthreshold insomnia; 15 to 21 = clinical insomnia (moderate severity); 22 to 28 = clinical insomnia (severe).
Time Frame
LTE Baseline (BL), LTE Week 24
Title
Percentage of Participants Requiring Addition of Standard of Care (SOC) Pericarditis Therapy Every 4 Weeks Cumulatively in the LTE Period
Time Frame
LTE Period, through LTE Follow up (up to Week 24)
Title
Change From LTE Baseline in Pericardial Signs in ECHO
Time Frame
LTE Baseline, LTE Week 24
Title
Change From LTE Baseline in Pericardial Signs in ECG
Time Frame
LTE Baseline, LTE Week 24
Title
Change From LTE Baseline in Pericardial Signs in MRI
Time Frame
LTE Baseline, LTE Week 24
Title
Number of Participants With Pericardial Delayed Hyperenhancement, Myocardial Delayed Hyperenhancement or Pericardial Effusion at LTE Period Week 24
Time Frame
LTE Week 24
Title
Annualized Rate of Pericarditis Recurrence in LTE Periods Based on Investigator's Assessment
Description
Annualized Recurrence Rate is defined as number of recurrences in LTE periods for all participants/Sum of participant years in LTE period for all participants. Participant years in LTE period is defined as the time from 1st dose date of LTE period to the date of End of Study, or data cutoff date, whichever is earlier. The 95% CI was calculated using an exact method with Poisson distribution.
Pericarditis recurrence was defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis. At any time during the RW period, participants who experienced a suspected recurrence of pericarditis symptoms reported to the study site/clinic for a scheduled or unscheduled visit, during which clinical assessments were performed to gather all the necessary diagnostic data to confirm or rule out the presence of pericarditis recurrence.
Time Frame
LTE Period, through LTE Follow up (up to Week 48)
Title
Annualized Rate of Pericarditis Recurrence in RW Period Based on CEC Adjudication
Description
Annualized Recurrence Rate is defined as the number of recurrences in RW period for all participants/Sum of participant years in RW period for all participants. Participant years in RW period is defined as the time from randomization date to the date of EORW or last dose date + 6 weeks, whichever is earlier. The 95% CI was calculated using an exact method with Poisson distribution.
Pericarditis recurrence was defined as the recurrence of typical pericarditis pain associated with supportive objective evidence of pericarditis. At any time during the RW period, participants who experienced a suspected recurrence of pericarditis symptoms reported to the study site/clinic for a scheduled or unscheduled visit, during which clinical assessments were performed to gather all the necessary diagnostic data to confirm or rule out the presence of pericarditis recurrence.
Time Frame
RW Period (mean 24.8 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Male or female aged 12 or older
Has a diagnosis of recurrent pericarditis
Must provide Informed Consent
Presents with at least the third episode of pericarditis during screening.
Has received nonsteroidal anti-inflammatory drugs (NSAIDs) and/or colchicine and/or corticosteroids (in any combination), if used, at stable dose levels (or at least not increased) for at least 3 days prior to first study drug administration
Female subjects must be postmenopausal, or incapable of pregnancy or permanently sterile, or if of childbearing potential must agree to use highly-effective method of contraception.
Must be up-to-date with all immunizations, in agreement with current local immunization guidelines for immunosuppressed subjects, before first study drug administration.
Is able to adequately maintain a daily subject diary according to protocol.
Agrees to refrain from making any new, major lifestyle changes that may affect pericarditis symptoms (e.g., changing exercise pattern) from the time that the informed consent form (ICF) is signed through the end of the double-blind randomized withdrawal period.
Key Exclusion Criteria:
Has a diagnosis of pericarditis that is secondary to specific prohibited etiologies.
Has a history of immunosuppression, including positive human immunodeficiency virus (HIV) test results.
Has a history of myeloproliferative disorder.
Has a history of demyelinating disease or symptoms suggestive of multiple sclerosis.
Has a history of active or latent tuberculosis (TB) prior to screening
Has chest x-ray at screening or within 12 weeks before receiving first administration of study drug, with evidence of malignancy or abnormality consistent with prior or active TB infection.
Has a history of positive or intermediate results for hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus antibody at screening.
Has a history of malignancy of any organ system within the past 5 years before screening (other than a successfully treated non metastatic cutaneous squamous cell carcinoma or basal cell carcinoma and/or localized carcinoma in situ of the cervix).
Has a known or suspected current active infection or a history of chronic or recurrent infectious disease, including, but not limited to, chronic renal infection, chronic chest infection, sinusitis, recurrent urinary tract infection, or an open, draining infected skin wound.
Has had an organ transplant.
In the Investigator's opinion, has a history of alcoholism or drug/chemical abuse within 2 years before screening.
Has a known hypersensitivity to rilonacept or to any of its excipients.
Has received an investigational drug during the 30 days before screening or is planning to receive an investigational drug (other than that administered during this study) or use an investigational device at any time during the study.
In the Investigator's opinion, has any other medical condition that could adversely affect the subject's participation or interfere with study evaluations.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Operations Study Director
Organizational Affiliation
Kiniksa Pharmaceuticals (UK), Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Cedars-Sinai Medical Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Arthritis and Rheumatology of Georgia
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
The Loretto Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60644
Country
United States
Facility Name
Minneapolis Heart Institute Foundation
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55407
Country
United States
Facility Name
Mayo Clinic - PPDS
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55902
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Cardiology Consultants of Philadelphia
City
Yardley
State/Province
Pennsylvania
ZIP/Postal Code
19067
Country
United States
Facility Name
Intermountain Healthcare
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
University Of Vermont Medical Center
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Swedish Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
HeartCare Partners Clinical Research Unit
City
Milton
State/Province
Queensland
ZIP/Postal Code
40664
Country
Australia
Facility Name
GenesisCare - Cardiology Research
City
Doncaster East
State/Province
Victoria
ZIP/Postal Code
3109
Country
Australia
Facility Name
Bnai Zion Medical Center
City
Haifa
Country
Israel
Facility Name
Shaare Zedek Medical Center
City
Jerusalem
Country
Israel
Facility Name
Galilee Medical Center
City
Nahariya
Country
Israel
Facility Name
Sheba Medical Center at Tel-Hashomer
City
Ramat Gan
Country
Israel
Facility Name
Ospedale Pediatrico Bambino Gesù
City
Roma
State/Province
Lazio
Country
Italy
Facility Name
ASST Fatebenefratelli Sacco - Ospedale Fatebenefratelli e Oftalmico
City
Milan
State/Province
Lombardy
Country
Italy
Facility Name
Azienda Ospedaliera Città della Salute e della Scienza di Torino
City
Turin
State/Province
Piedmont
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33200890
Citation
Klein AL, Imazio M, Cremer P, Brucato A, Abbate A, Fang F, Insalaco A, LeWinter M, Lewis BS, Lin D, Luis SA, Nicholls SJ, Pano A, Wheeler A, Paolini JF; RHAPSODY Investigators. Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis. N Engl J Med. 2021 Jan 7;384(1):31-41. doi: 10.1056/NEJMoa2027892. Epub 2020 Nov 16.
Results Reference
background
PubMed Identifier
36316102
Citation
Brucato A, Wheeler A, Luis SA, Abbate A, Cremer PC, Zou L, Insalaco A, Lewinter M, Lewis BS, Lin D, Nicholls S, Pancrazi M, Klein AL, Imazio M, Paolini JF. Transition to rilonacept monotherapy from oral therapies in patients with recurrent pericarditis. Heart. 2023 Jan 27;109(4):297-304. doi: 10.1136/heartjnl-2022-321328.
Results Reference
derived
PubMed Identifier
36250662
Citation
Brucato A, Lim-Watson MZ, Klein A, Imazio M, Cella D, Cremer P, LeWinter MM, Luis SA, Lin D, Lotan D, Pancrazi M, Trotta L, Klooster B, Litcher-Kelly L, Zou L, Magestro M, Wheeler A, Paolini JF; RHAPSODY Investigators. Interleukin-1 Trap Rilonacept Improved Health-Related Quality of Life and Sleep in Patients With Recurrent Pericarditis: Results From the Phase 3 Clinical Trial RHAPSODY. J Am Heart Assoc. 2022 Oct 18;11(20):e023252. doi: 10.1161/JAHA.121.023252. Epub 2022 Oct 17.
Results Reference
derived
PubMed Identifier
32866928
Citation
Klein AL, Imazio M, Brucato A, Cremer P, LeWinter M, Abbate A, Lin D, Martini A, Beutler A, Chang S, Fang F, Gervais A, Perrin R, Paolini JF. RHAPSODY: Rationale for and design of a pivotal Phase 3 trial to assess efficacy and safety of rilonacept, an interleukin-1alpha and interleukin-1beta trap, in patients with recurrent pericarditis. Am Heart J. 2020 Oct;228:81-90. doi: 10.1016/j.ahj.2020.07.004. Epub 2020 Jul 14.
Results Reference
derived
Learn more about this trial
Study to Assess the Efficacy and Safety of Rilonacept Treatment in Participants With Recurrent Pericarditis
We'll reach out to this number within 24 hrs