Back to resultsA Placebo-controlled Phase 2 Trial to Investigate the Safety and Efficacy of Secukinumab in Giant Cell Arteritis (TitAIN)
Primary Purpose
Giant Cell Arteritis
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Secukinumab 300 mg, s.c.
Prednisolone
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Giant Cell Arteritis focused on measuring GCA, ain457, Secukinumab, Subcutaneous, Vessel Inflammation, corticosteroid tapering, newly diagnosed or relapsing giant cell arteritis, prednisolone taper regimen, "escape"
Eligibility Criteria
Inclusion Criteria:
Diagnosis of GCA classified according to the following criteria:
- Age at onset of disease ≥ 50 years.
- History of ESR ≥ 30 mm/hr or CRP ≥ 10 mg/L.
- Unequivocal cranial symptoms of GCA (new-onset localized headache, scalp or temporal artery tenderness, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication) AND/OR symptoms of polymyalgia rheumatica (PMR) defined as shoulder and/or hip girdle pain associated with inflammatory morning stiffness
- Temporal artery biopsy revealing features of GCA AND/OR
- evidence of large-vessel vasculitis by angiography or cross-sectional imaging study such as magnetic resonance angiography (MRA), computed tomography angiography (CTA), positron emission tomography-computed tomography (PET CT), or ultrasound
Patients with new onset GCA or relapsing GCA (Definition new onset: diagnosis of GCA within 6 weeks of Baseline Visit; Definition relapsing GCA: diagnosis of GCA (in accordance with inclusion criterion no. 4) > 6 weeks before Baseline Visit and in the meantime achieved remission (absence of signs and symptoms attributable to GCA and normalization of ESR (< 30 mm/hr) and CRP (<10.0mg/L) included) including previous treatment with ≥ 25 mg/day prednisolone equivalent for ≥ 2 weeks.)
Active disease as defined by the presence of signs and symptoms of GCA (cranial or PMR) and elevated ESR ≥ 30 mm/hr, or CRP ≥ 10 mg/L, attributed to active GCA within 6 weeks of Baseline.
Prednisolone dose of 25-60 mg/day at Baseline.
Exclusion Criteria:
Previous exposure to secukinumab or other biologic drug directly targeting Interleukin(IL)-17 or IL-17 receptor.
Patients treated with any cell-depleting therapies including but not limited to anti-CD20 or investigational agents (e.g. anti-CD3, anti-CD4, anti-CD5 or anti-CD19).
Patients who have previously been treated with any biologic agent including but not limited to tocilizumab, sirukumab, abatacept, or tumor necrosis factor alpha (TNFα) inhibitors (infliximab, adalimumab, etanercept, certolizumab, golimumab).
Patients who have previously been treated with tofacitinib or baricitinib.
Patients treated with i.v. immunoglobulins or plasmapheresis within 8 weeks prior to Baseline.
Patients treated with cyclophosphamide, tacrolimus or everolimus within 6 months prior to Baseline.
Patients treated with hydroxychloroquine, cyclosporine A, azathioprine, sulfasalazine or mycophenolate mofetil within 4 weeks of Baseline.
Patients treated with leflunomide within 8 weeks of Baseline unless a cholestyramine washout has been performed in which case the patient must be treated within 4 weeks of Baseline.
Patients treated with an alkylating agent except for cyclophosphamide as mentioned above.
Patients requiring systemic chronic glucocorticoid therapy for any other reason than GCA.
Chronic systemic glucocorticoid therapy over the last 4 years or longer; or inability, in the opinion of the investigator, to withdraw glucocorticoid therapy through protocol-defined taper regimen due to suspected or established adrenal insufficiency.
Patients requiring chronic (i.e. not occasional "prn") high potency opioid analgesics for pain management.
Active ongoing inflammatory diseases or underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions, which in the opinion of the investigator immunosuppressed the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy.
History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum creatinine level exceeding 1.8 mg/dL (159.12 μmol/L).
Screening total white blood cell (WBC) count < 3000/μL, or platelets < 100 000/μL or neutrophils < 1500/μL or hemoglobin < 8.3 g/dL (83 g/L).
Major ischemic event, unrelated to GCA, within 12 weeks of screening.
Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C at screening or randomization.
Life vaccinations within 6 weeks prior to Baseline or planned vaccination during study participation until 12 weeks after last study treatment administration.
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Secukinumab
Placebo
Arm Description
Participants received secukinumab at a dose of 300 milligrams (mg) as subcutaneous (s.c.) injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter through to week 48 along with a 26-week prednisolone tapering regimen.
Participants received placebo as subcutaneous (s.c.) injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter through to week 48 along with a 26-week prednisolone tapering regimen.
Outcomes
Primary Outcome Measures
Percentage of Participants in Sustained Remission Until Week 28
Remission was defined as the absence of flare. Sustained remission was defined as the absence of flare until Week 28 and in adherence to the protocol prednisolone taper regimen.
Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of Giant Cell Arteritis (GCA) and/or erythrocyte sedimentation rate (ESR) greater than or equal to (>/=) 30 millimeters per hour (mm/hr) and/or C-reactive Protein (CRP) (>/=10.0 mg/L) attributable to GCA.
Patients were classified as non-responders if they did not achieve remission within 12 weeks of Baseline (remission referred to the absence of flare), were in the "escape arm" (this referred to patients entering escape between Baseline and Week 28), prematurely discontinued study treatment prior to Week 28 (absence of flare was checked prior to study treatment administration), did not have information to evaluate sustained remission response until Week 28.
Secondary Outcome Measures
Percentage of Participants in Remission at Week 12
Remission was defined as the absence of flare. Sustained remission was defined as the absence of flare until Week 28 and in adherence to the protocol prednisolone taper Regimen.
Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (>/=) 30 millimeters per hour (mm/hr) and/or CRP (>/=10.0 mg/L) attributable to GCA.
Patients were classified as non-responders if they did not achieve remission within 12 weeks of Baseline (remission referred to the absence of flare), were in the "escape arm" (this referred to patients entering escape between Baseline and Week 28), prematurely discontinued study treatment prior to Week 28 (absence of flare was checked prior to study treatment administration), did not have information to evaluate sustained remission response until Week 28.
Time to First GCA Flare After Clinical Remission
Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (>/=) 30 millimeters per hour (mm/hr) and/or CRP (>/=10.0 mg/L) attributable to GCA. Time to first flare after remission referred to time from first day of study treatment until first post-Baseline flare.
For time to first GCA flare after remission (up to and including Week 52), patients who prematurely discontinued study treatment prior to Week 52 were censored at the time of premature discontinuation and patients who completed treatment and did not have a flare were censored at their last visit in the treatment phase.
Time to first GCA flare after remission was calculated using Kaplan-Meier plot of time.
Total Cumulative Prednisolone Dose Over 28 Weeks and 52 Weeks
Total cumulative co-administered prednisolone treatment was summarized over time by treatment arm. Patients received a daily dose of prednisolone, which was decreased (i.e. tapered down) from Baseline to Week 26. No additional prednisolone or equivalent was permitted.
Percentage of Participants With GCA Who Had Sustained Remission Until Week 52
Remission was defined as the absence of flare. Sustained remission was defined as patients without flare until Week 52 and in adherence to the protocol prednisolone taper regimen plus prednisolone-free phase from Week 27 onwards. Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (>/=) 30 millimeters per hour (mm/hr) and/or CRP (>/=10.0 mg/L) attributable to GCA.
Patients were classified as non-responders if they did not achieve remission within 12 weeks of Baseline (remission referred to the absence of flare), were in the "escape arm" (this referred to patients entering escape between Baseline and Week 28), prematurely discontinued study treatment prior to Week 28 (absence of flare was checked prior to study treatment administration), did not have information to evaluate sustained remission response until Week 28.
Number of Participants on Prednisolone Dose ≤ 5mg/Day
Number of participants on co-administered prednisolone treatment ≤ 5mg/day who responded at Week 19, Week 26 and Week 52.
Remission was defined as the absence of flare. Sustained remission was defined as the absence of flare until Week 28 and in adherence to the protocol prednisolone taper Regimen. There were 2 taper regimens: for patients on 40 to 60 mg/day prednisolone at Baseline and for patients on 25 to 40 mg/day prednisolone at Baseline depending on patients' prednisolone levels at Baseline. Prednisolone was tapered from a dose of 25 mg to 60 mg at Baseline to 1 mg at Week 26 [last dose].
Physicians Global Assessment (PhGA) of Disease Activity: Change From Baseline Score Via Visual Analogue Scale (VAS)
Clinician Reported Outcome: Physicians global assessment (PhGA) using a visual analogue scale (VAS) scale. VAS is a range of scores from 0-100, with lower change from baseline scores indicating a more favorable outcome and higher change from baseline scores indicating a greater disease activity.
Patients Global Assessment (PGA) of Disease Activity: Change From Baseline Via Visual Analogue Scale (VAS)
Patient Reported Outcome: Patients global assessment (PGA) score using a VAS scale. VAS is a range of scores from 0-100, with lower change from baseline scores indicating a more favorable outcome and higher change from baseline scores indicating a greater disease activity.
Change From Baseline in FACIT-Fatigue Scale
Patient Reported Outcome: Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue is a 13-item questionnaire with a full scale of 0 -52 that assesses self-reported fatigue and its impact upon daily activities and function. The higher the score the better functioning (less fatigue).
Change From Baseline in Short-Form (SF)-36 Questionnaire
Patient Reported Outcome: The SF-36 is a standardized questionnaire used to measure health-related quality of life among healthy patients and patients with acute and chronic conditions. It consists of 8 subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. The higher the score (change from baseline) the more favorable the outcome. The values were reported by change from baseline in SF-36 domain scores.
Change From Baseline in EQ-5D-5L (EuroQol 5D) Questionnaire
EQ-5D-5L, a self-administered questionnaire assessing health status in adults, is divided into 2 sections. The 1st section addresses 5 dimensions (mobility, self-care, usual activity, pain/discomfort, & anxiety/depression). Items are rated either "no problem", "slight problems", "moderate problems", "severe problems", or "extreme problems/unable." A composite health index is defined by combining the levels for each dimension. The 2nd section measures self-rated (global) health status via vertically oriented VAS where 100 represents the "best possible health state" & 0 represents the "worst possible health state." The EQ-5D-5L contains 6 items assessing health status via a single index value or health utility score and allows "weighting" by the patient of health states & generation of patient utilities. Published weights are available allowing for creation of a single summary health utility score. Scores range from 0 to 1, with lower scores representing a higher level of dysfunction.
Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
ESR is a laboratory test that provides a non-specific measure of inflammation. This was assessed in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation.
Change From Baseline in C-Reactive Protein (CRP) Level
The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. This was assessed in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
Full Information
NCT ID
NCT03765788
First Posted
December 3, 2018
Last Updated
August 16, 2023
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03765788
Brief Title
A Placebo-controlled Phase 2 Trial to Investigate the Safety and Efficacy of Secukinumab in Giant Cell Arteritis
Acronym
TitAIN
Official Title
A Randomized, Parallel-group, Double-blind, Placebo-controlled, Multicenter Phase 2 Trial to Investigate the Safety and Efficacy of Secukinumab (AIN457) in Patients With Giant Cell Arteritis (TitAIN)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
January 30, 2019 (Actual)
Primary Completion Date
June 8, 2021 (Actual)
Study Completion Date
June 8, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study was designed to evaluate the efficacy and safety of secukinumab compared to placebo to maintain disease remission up to 28 weeks including corticosteroid tapering, as well as up to 1 year (52 weeks) in patients with newly diagnosed or relapsing giant cell arteritis (GCA) who were naïve to biological therapy.
Detailed Description
This randomized, parallel-group, double-blind, placebo-controlled, multicenter, Phase II study was designed to evaluate the efficacy of secukinumab compared to placebo in combination with a 26-week prednisolone taper regimen in terms of sustained remission in patients with newly diagnosed or relapsing Giant Cell Arteritis (GCA) who were naïve to biological therapy. The study consisted of a Screening Period of up to 6 weeks (maximum duration), a 52-week Treatment Period and an 8-week Safety Follow-up Period
Patients who did not achieve remission by Week 12, experienced a flare after remission or could not adhere to the prednisolone taper regimen entered "escape". Upon entering "escape", patients received prednisolone at a dose determined by the physician's clinical judgment and continued to receive secukinumab or placebo in a blinded manner.
Safety evaluation was included in all visits including two safety follow-up visits performed 8 and 12 weeks after the last study drug administration.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Giant Cell Arteritis
Keywords
GCA, ain457, Secukinumab, Subcutaneous, Vessel Inflammation, corticosteroid tapering, newly diagnosed or relapsing giant cell arteritis, prednisolone taper regimen, "escape"
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Secukinumab
Arm Type
Experimental
Arm Description
Participants received secukinumab at a dose of 300 milligrams (mg) as subcutaneous (s.c.) injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter through to week 48 along with a 26-week prednisolone tapering regimen.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo as subcutaneous (s.c.) injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter through to week 48 along with a 26-week prednisolone tapering regimen.
Intervention Type
Drug
Intervention Name(s)
Secukinumab 300 mg, s.c.
Other Intervention Name(s)
AIN457
Intervention Description
Secukinumab 300 mg was administered by subcutaneous (s.c.) injections using 1 mL pre-filled syringes (PFSs) throughout the study.
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
Prednisolone was provided as tablets (1 mg, 5 mg, 10 mg, 20 mg tablets) for daily administration as tapered regimen from a dose of 25 mg to 60 mg at Baseline to 1 mg at Week 26 (last dose)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo 300 mg was administered by subcutaneous (s.c.) injections using 1 mL pre-filled syringes (PFSs) throughout the study.
Primary Outcome Measure Information:
Title
Percentage of Participants in Sustained Remission Until Week 28
Description
Remission was defined as the absence of flare. Sustained remission was defined as the absence of flare until Week 28 and in adherence to the protocol prednisolone taper regimen.
Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of Giant Cell Arteritis (GCA) and/or erythrocyte sedimentation rate (ESR) greater than or equal to (>/=) 30 millimeters per hour (mm/hr) and/or C-reactive Protein (CRP) (>/=10.0 mg/L) attributable to GCA.
Patients were classified as non-responders if they did not achieve remission within 12 weeks of Baseline (remission referred to the absence of flare), were in the "escape arm" (this referred to patients entering escape between Baseline and Week 28), prematurely discontinued study treatment prior to Week 28 (absence of flare was checked prior to study treatment administration), did not have information to evaluate sustained remission response until Week 28.
Time Frame
Until week 28
Secondary Outcome Measure Information:
Title
Percentage of Participants in Remission at Week 12
Description
Remission was defined as the absence of flare. Sustained remission was defined as the absence of flare until Week 28 and in adherence to the protocol prednisolone taper Regimen.
Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (>/=) 30 millimeters per hour (mm/hr) and/or CRP (>/=10.0 mg/L) attributable to GCA.
Patients were classified as non-responders if they did not achieve remission within 12 weeks of Baseline (remission referred to the absence of flare), were in the "escape arm" (this referred to patients entering escape between Baseline and Week 28), prematurely discontinued study treatment prior to Week 28 (absence of flare was checked prior to study treatment administration), did not have information to evaluate sustained remission response until Week 28.
Time Frame
Week 12
Title
Time to First GCA Flare After Clinical Remission
Description
Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (>/=) 30 millimeters per hour (mm/hr) and/or CRP (>/=10.0 mg/L) attributable to GCA. Time to first flare after remission referred to time from first day of study treatment until first post-Baseline flare.
For time to first GCA flare after remission (up to and including Week 52), patients who prematurely discontinued study treatment prior to Week 52 were censored at the time of premature discontinuation and patients who completed treatment and did not have a flare were censored at their last visit in the treatment phase.
Time to first GCA flare after remission was calculated using Kaplan-Meier plot of time.
Time Frame
Up to Week 52 (included)
Title
Total Cumulative Prednisolone Dose Over 28 Weeks and 52 Weeks
Description
Total cumulative co-administered prednisolone treatment was summarized over time by treatment arm. Patients received a daily dose of prednisolone, which was decreased (i.e. tapered down) from Baseline to Week 26. No additional prednisolone or equivalent was permitted.
Time Frame
from Baseline to week 28, from baseline to week 52 weeks
Title
Percentage of Participants With GCA Who Had Sustained Remission Until Week 52
Description
Remission was defined as the absence of flare. Sustained remission was defined as patients without flare until Week 52 and in adherence to the protocol prednisolone taper regimen plus prednisolone-free phase from Week 27 onwards. Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of GCA and/or erythrocyte sedimentation rate (ESR) greater than or equal to (>/=) 30 millimeters per hour (mm/hr) and/or CRP (>/=10.0 mg/L) attributable to GCA.
Patients were classified as non-responders if they did not achieve remission within 12 weeks of Baseline (remission referred to the absence of flare), were in the "escape arm" (this referred to patients entering escape between Baseline and Week 28), prematurely discontinued study treatment prior to Week 28 (absence of flare was checked prior to study treatment administration), did not have information to evaluate sustained remission response until Week 28.
Time Frame
Until Week 52
Title
Number of Participants on Prednisolone Dose ≤ 5mg/Day
Description
Number of participants on co-administered prednisolone treatment ≤ 5mg/day who responded at Week 19, Week 26 and Week 52.
Remission was defined as the absence of flare. Sustained remission was defined as the absence of flare until Week 28 and in adherence to the protocol prednisolone taper Regimen. There were 2 taper regimens: for patients on 40 to 60 mg/day prednisolone at Baseline and for patients on 25 to 40 mg/day prednisolone at Baseline depending on patients' prednisolone levels at Baseline. Prednisolone was tapered from a dose of 25 mg to 60 mg at Baseline to 1 mg at Week 26 [last dose].
Time Frame
Week 19, Week 28, Week 52
Title
Physicians Global Assessment (PhGA) of Disease Activity: Change From Baseline Score Via Visual Analogue Scale (VAS)
Description
Clinician Reported Outcome: Physicians global assessment (PhGA) using a visual analogue scale (VAS) scale. VAS is a range of scores from 0-100, with lower change from baseline scores indicating a more favorable outcome and higher change from baseline scores indicating a greater disease activity.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52
Title
Patients Global Assessment (PGA) of Disease Activity: Change From Baseline Via Visual Analogue Scale (VAS)
Description
Patient Reported Outcome: Patients global assessment (PGA) score using a VAS scale. VAS is a range of scores from 0-100, with lower change from baseline scores indicating a more favorable outcome and higher change from baseline scores indicating a greater disease activity.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52
Title
Change From Baseline in FACIT-Fatigue Scale
Description
Patient Reported Outcome: Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue is a 13-item questionnaire with a full scale of 0 -52 that assesses self-reported fatigue and its impact upon daily activities and function. The higher the score the better functioning (less fatigue).
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52
Title
Change From Baseline in Short-Form (SF)-36 Questionnaire
Description
Patient Reported Outcome: The SF-36 is a standardized questionnaire used to measure health-related quality of life among healthy patients and patients with acute and chronic conditions. It consists of 8 subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. The higher the score (change from baseline) the more favorable the outcome. The values were reported by change from baseline in SF-36 domain scores.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52
Title
Change From Baseline in EQ-5D-5L (EuroQol 5D) Questionnaire
Description
EQ-5D-5L, a self-administered questionnaire assessing health status in adults, is divided into 2 sections. The 1st section addresses 5 dimensions (mobility, self-care, usual activity, pain/discomfort, & anxiety/depression). Items are rated either "no problem", "slight problems", "moderate problems", "severe problems", or "extreme problems/unable." A composite health index is defined by combining the levels for each dimension. The 2nd section measures self-rated (global) health status via vertically oriented VAS where 100 represents the "best possible health state" & 0 represents the "worst possible health state." The EQ-5D-5L contains 6 items assessing health status via a single index value or health utility score and allows "weighting" by the patient of health states & generation of patient utilities. Published weights are available allowing for creation of a single summary health utility score. Scores range from 0 to 1, with lower scores representing a higher level of dysfunction.
Time Frame
Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52
Title
Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
Description
ESR is a laboratory test that provides a non-specific measure of inflammation. This was assessed in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. The test assesses the rate at which red blood cells fall in a test tube. Normal range is 0-30 mm/hr. A higher rate is consistent with inflammation.
Time Frame
Baseline, Week 28, Week 52
Title
Change From Baseline in C-Reactive Protein (CRP) Level
Description
The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. This was assessed in order to identify the presence of inflammation, to determine its severity, and to monitor response to treatment. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
Time Frame
Baseline, Week 28, Week 52
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of GCA classified according to the following criteria:
Age at onset of disease ≥ 50 years.
History of ESR ≥ 30 mm/hr or CRP ≥ 10 mg/L.
Unequivocal cranial symptoms of GCA (new-onset localized headache, scalp or temporal artery tenderness, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication) AND/OR symptoms of polymyalgia rheumatica (PMR) defined as shoulder and/or hip girdle pain associated with inflammatory morning stiffness
Temporal artery biopsy revealing features of GCA AND/OR
evidence of large-vessel vasculitis by angiography or cross-sectional imaging study such as magnetic resonance angiography (MRA), computed tomography angiography (CTA), positron emission tomography-computed tomography (PET CT), or ultrasound
Patients with new onset GCA or relapsing GCA (Definition new onset: diagnosis of GCA within 6 weeks of Baseline Visit; Definition relapsing GCA: diagnosis of GCA (in accordance with inclusion criterion no. 4) > 6 weeks before Baseline Visit and in the meantime achieved remission (absence of signs and symptoms attributable to GCA and normalization of ESR (< 30 mm/hr) and CRP (<10.0mg/L) included) including previous treatment with ≥ 25 mg/day prednisolone equivalent for ≥ 2 weeks.)
Active disease as defined by the presence of signs and symptoms of GCA (cranial or PMR) and elevated ESR ≥ 30 mm/hr, or CRP ≥ 10 mg/L, attributed to active GCA within 6 weeks of Baseline.
Prednisolone dose of 25-60 mg/day at Baseline.
Exclusion Criteria:
Previous exposure to secukinumab or other biologic drug directly targeting Interleukin(IL)-17 or IL-17 receptor.
Patients treated with any cell-depleting therapies including but not limited to anti-CD20 or investigational agents (e.g. anti-CD3, anti-CD4, anti-CD5 or anti-CD19).
Patients who have previously been treated with any biologic agent including but not limited to tocilizumab, sirukumab, abatacept, or tumor necrosis factor alpha (TNFα) inhibitors (infliximab, adalimumab, etanercept, certolizumab, golimumab).
Patients who have previously been treated with tofacitinib or baricitinib.
Patients treated with i.v. immunoglobulins or plasmapheresis within 8 weeks prior to Baseline.
Patients treated with cyclophosphamide, tacrolimus or everolimus within 6 months prior to Baseline.
Patients treated with hydroxychloroquine, cyclosporine A, azathioprine, sulfasalazine or mycophenolate mofetil within 4 weeks of Baseline.
Patients treated with leflunomide within 8 weeks of Baseline unless a cholestyramine washout has been performed in which case the patient must be treated within 4 weeks of Baseline.
Patients treated with an alkylating agent except for cyclophosphamide as mentioned above.
Patients requiring systemic chronic glucocorticoid therapy for any other reason than GCA.
Chronic systemic glucocorticoid therapy over the last 4 years or longer; or inability, in the opinion of the investigator, to withdraw glucocorticoid therapy through protocol-defined taper regimen due to suspected or established adrenal insufficiency.
Patients requiring chronic (i.e. not occasional "prn") high potency opioid analgesics for pain management.
Active ongoing inflammatory diseases or underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions, which in the opinion of the investigator immunosuppressed the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy.
History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum creatinine level exceeding 1.8 mg/dL (159.12 μmol/L).
Screening total white blood cell (WBC) count < 3000/μL, or platelets < 100 000/μL or neutrophils < 1500/μL or hemoglobin < 8.3 g/dL (83 g/L).
Major ischemic event, unrelated to GCA, within 12 weeks of screening.
Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C at screening or randomization.
Life vaccinations within 6 weeks prior to Baseline or planned vaccination during study participation until 12 weeks after last study treatment administration.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01067
Country
Germany
Facility Name
Novartis Investigative Site
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Novartis Investigative Site
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Novartis Investigative Site
City
Germering
ZIP/Postal Code
82110
Country
Germany
Facility Name
Novartis Investigative Site
City
Herne
ZIP/Postal Code
44649
Country
Germany
Facility Name
Novartis Investigative Site
City
Koeln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Novartis Investigative Site
City
Ludwigshafen
ZIP/Postal Code
67063
Country
Germany
Facility Name
Novartis Investigative Site
City
Luebeck
ZIP/Postal Code
23538
Country
Germany
Facility Name
Novartis Investigative Site
City
Trier
ZIP/Postal Code
54292
Country
Germany
Facility Name
Novartis Investigative Site
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
IPD Sharing URL
https://www.clinicalstudydatarequest.com
Citations:
PubMed Identifier
34404463
Citation
Venhoff N, Schmidt WA, Lamprecht P, Tony HP, App C, Sieder C, Legeler C, Jentzsch C, Thiel J. Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial. Trials. 2021 Aug 17;22(1):543. doi: 10.1186/s13063-021-05520-1.
Results Reference
derived
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217151&parentIdentifier=CAIN457ADE11C&attachmentIdentifier=99008743-0238-47ae-a207-9328edbb241c&fileName=Clinical_Trials_Results_Word_Form-CAIN457ADE11C.docx&versionIdentifier=
Description
Clinical_Trials_Results_Word_Form-CAIN457ADE11C.docx attachment has been refreshed from the Clinical Trials Results Word Form template. Data may be populated from the following (as available) : Study (70.0), Protocol (4.22), Results(0.22)
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1080
Description
A Plain Language Trial Summary is available on novctrd.com
Learn more about this trial
A Placebo-controlled Phase 2 Trial to Investigate the Safety and Efficacy of Secukinumab in Giant Cell Arteritis
We'll reach out to this number within 24 hrs