Long-term Safety and Tolerability of Atacicept (Long-term Follow-Up of Participant Who Participated in ADDRESS II)
Primary Purpose
Lupus Erythematosus, Systemic
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Atacicept 75 mg
Atacicept 150 mg
Atacicept 150 mg
Sponsored by
About this trial
This is an interventional treatment trial for Lupus Erythematosus, Systemic focused on measuring Lupus Erythematosus, Systemic, Atacicept 75 and 150 mg, LTE
Eligibility Criteria
Inclusion Criteria:
- Participants who had completed the 24-week treatment period of study EMR-700461-023 (ADDRESS II core trial)
- Women of childbearing potential who had a negative pregnancy test
- Other protocol defined inclusion criteria were applied
Exclusion Criteria:
- Active neurological symptoms of SLE that were deemed severe or progressive
- Diagnosis of any demyelinating disease, such as, but not restricted to, multiple sclerosis (MS) or optic neuritis
- Pregnancy
- Active clinically significant viral, bacterial, or fungal infection, or any major episode of infection that in the investigator's opinion makes the participants unsuitable to continued participation in the study
- Other protocol defined exclusion criteria were applied
Sites / Locations
- Pinnacle Research Group LLC
- University of Alabama at Birmingham - (UAB)
- Wallace Rheumatic Study Center
- Southern California Permenent Medical Group
- East Bay Rheumatology Medical Group, Inc.
- Clinical Research of West Florida - Corporate
- Clinical Research of West Florida, Inc.
- McIlwain Medical Group, PA
- AA MRC LLC Ahmed Arif Medical Research Center
- Mayo Clinic
- Washington University
- Clayton Medical Associates, P.C.
- Rutgers New Jersey Medical School
- The Feinstein Institute for Medical Research
- Hospital for Special Surgery
- DJL Clinical Research, PLLC
- MetroHealth System
- Arthritis & Rheumatology Center of Oklahoma
- OMRF
- Clinical Research Center of Reading LLC
- Medical University of South Carolina (MUSC)
- Austin Regional Clinic, P.A.
- Little River Arthritis & Osteoporosis Clinic
- Instituto CAICI
- Centro Medico Privado de Reumatologia
- Investigaciones Clinicas Tucuman
- Centro Integral de Reumatologia
- Organizacion Medica de Investigacion (OMI)
- APRILLUS
- Atencion Integral en Reumatologia (AIR)
- Hospital Privado Centro Medico de Cordoba
- Cordis S.A.
- Centro Polivalente de Asistencia e Inv. Clinica CER
- Centro de Pesquisas em Diabetes Ltda.
- MHAT "Eurohospital" - Plovdiv, OOD
- Medical Center "Teodora", EOOD
- MHAT - Ruse, AD
- UMHAT "Sv. Ivan Rilski", EAD
- DCC "Sveta Anna", EOOD
- Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
- MHAT-Targovishte, AD
- Corporacion de Beneficencia Osorno
- Quantum Research Santiago
- Centro Medico Prosalud
- Biomedica
- Centro de Estudios Reumatologicos
- CINVEC - Centro de Investigacion Clinica V Region
- Revmatologicky Ustav
- Revmatologicka ambulance
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
- Charite Universitaetsmedizin Berlin - Campus Charite Mitte
- Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
- Seoul National University Hospital
- Ajou University Hospital
- Konkuk University Medical Center
- Hospital Universitario de Saltillo "Dr. Gonzalo Valdés Valdés"
- Clinstile, S.A. de C.V.
- Morales Vargas Centro de Investigacion, S.C.
- Icle S.C.
- Unidad de Investigacion en Enfermedades Cronico Degenerativas SC
- Clinica de Enfermedades Cronicas y de Procedimientos Especiales, S.C.
- Accelerium S. de R.L. de C.V.
- Centro Multidisciplinario para el desarrollo Especializado de la Investigacion Clinica en Yucatan
- Investigacion y Biomedicina de Chihuahua, S.C.
- Hogar Clínica San Juan de Dios - Arequipa
- Clinica Medica Cayetano Heredia
- Invest Clinicas Sac Inst de Ginecologia y Reproduccion
- Angeles University Foundation Medical Center
- Mary Mediatrix Medical Center
- Davao Doctors Hospital
- Iloilo Doctors Hospital
- Szpital Uniwersytecki nr 2 im.dr J. Biziela
- FSBEI HE " First Moscow State Medical University n.a. I.M. Sechenov" of the MoH of the RF
- SBIH of Republic Kareliya "Republican Hospital n.a. V.A. Baranov"
- SPb SBIH "Clinical Rheumatological Hospital # 25"
- SIH "Saratov City Clinical Hospital # 12"
- SBIH of Vladimir region "Regional Clinical Hospital"
- SBHI of Yaroslavl Region "Clinical Hospital # 8"
- Naidoo, A
- Winelands Medical Research Centre
- Hospital Clinico Universitario de Valladolid
- Queen's Hospital
- University College London Hospitals
- Guy's Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Atacicept 75 mg
Atacicept 150 mg
Placebo/Atacicept 150 mg
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With at Least One Serious Adverse Event (SAE) During the Treatment Period
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. Treatment- Emergent adverse events (TEAEs) during the treatment period exclude those ongoing at the time of study entry into 024 LTE Day 1 and exclude the safety follow-up period.
Number of Participants Who Prematurely Discontinued the Treatment Due to Adverse Event (AE)
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. TEAEs were defined as events with an onset date on or after the date of first dose of study treatment in the core study and ongoing at the 024 LTE study entry, occurring during the 024 LTE study and the Safety follow-up Period.
Secondary Outcome Measures
Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Organ Damage Scores
SLICC/ACR score or damage index evaluates cumulative damage in Systemic Lupus Erythematosus (SLE). These changes may or may not be related to SLE. Most items are scored only if they have been present for at least 6 months. Scores range from 0 to 47 points, with higher scores indicating greater cumulative damage. Baseline was defined as Day 1 of Core study.
Change From Baseline in Disease Activity as Measured by British Isles Lupus Assessment Group (BILAG) 2004 Score
BILAG Disease Activity Index evaluates systemic lupus erythematosus (SLE) activity in 8 organ system domains: General, mucocutaneous, neurological, musculoskeletal, cardiorespiratory, vasculitis, renal, and hematologic using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Severe disease activity; BILAG B: moderate disease activity; BILAG C: mild disease; BILAG D: system previously affected but now inactive; BILAG E: system never involved. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). The total BILAG score is the sum of the scores of the 8 domains where A=9, B=3, C=1, D=0, and E=0. The total score ranges from 0 to 72 with a higher score indicating greater lupus activity.
Change From Baseline in Disease Activity as Measured by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score
SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms). Baseline was defined as core study screening visit.
Change From Baseline in Disease Activity as Measured by SLEDAI-2K Responder Index-50 (SRI-50) Score
SRI-50 index was derived from SLEDAI-2K and could capture 50% or better improvement in each descriptor between any 2 visits in systemic lupus erythematosus (SLE) participants when there was incomplete resolution. The new assigned scores for the descriptors of SRI-50 were derived by dividing the score of each SLEDAI-2K descriptor by 2. SLEDAI-2K was an activity index that measured disease activity and records feature of active lupus as present or not present. SLEDAI-2K used a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present was assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranged from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Change From Baseline in Disease Activity as Measured by Physician's Global Assessment (PGA) Score
The PGA was used to quantify disease activity and was measured using an anchored visual analog scale (VAS). The participant's current disease activity assessed by investigator in the score range of 0 to 3. Where 0=none; 1=mild; 2=moderate; 3=severe. The assessment made relative not to the participant's most severe state, but the most severe state of systemic lupus erythematosus (SLE) per the investigator's assessment. Baseline was defined as core study screening visit.
Number of Participants Who Achieved SLE Responder Index (SRI-4) Response (a Disease Activity Composite Index)
SRI-4 response was defined as greater than or equal to 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline Physician's Global Assessment of Disease Activity (PGA). SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Number of Participants Who Achieved BILAG-based Combined Lupus Assessment (BICLA) Response (a Disease Activity Composite Index)
The BICLA response was defined as BILAG-2004 improvement (all screening visit BILAG A improving to B/C/D, all screening visit BILAG B to C/D, and less than or equal to (<=1) new BILAG B and no new BILAG A); no deterioration in SLEDAI total score; PGA increase by less than (<) 0 percentage (%) (defined as less then (<)0.3 point increase for the statistical analyses) and no non-permitted medication/treatment. Baseline was defined as core study screening visit.
Percent Change From Baseline in Prednisone-equivalent Corticosteroid Dose
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score
The 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) is based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100=highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100=highest level of physical functioning).
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score
The LupusQoL was a lupus-specific health related QoL (HRQoL) questionnaire consisting of 34 items grouped in 8 domains: physical health, pain, planning, intimate relationships, burden to others, emotional health, body image, and fatigue. Participants indicate their responses on a 5-point Likert response format, where 4 = never, 3 = occasionally, 2 = a good bit of the time, 1 = most of the time, and 0 = all of the time. Summary scores can be calculated for all 8 domains. A LupusQoL score for each domain was reported on a 0 to 100 scale, with greater values indicating better HRQoL. Baseline was defined as Day 1 of core study.
Number of Participants With Patient Global Impression of Change (PGIC)
The PGIC is self-rated scale that asks the participant to describe the change in activity limitations, symptoms, emotions, and overall Quality of life (QoL) related to the participant's painful condition on the following scale: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse) and 7 (very much worse). Number of participants in the PGIC categories of very much improved (1) and much improved (2) are reported.
Change From Baseline in EuroQoL 5 Dimension Instrument (EQ-5D) Score
EQ-5D questionnaire comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels; 1=no problem, 2=moderate problems, 3=extreme problems. This part, called the EQ-5D descriptive system, provides a 5-dimensional description of health status. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state. Baseline was defined as Day 1 of Core study.
Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores
EQ-5D is a participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 millimeters (mm) (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. Baseline defined as Day 1 of core study.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.
Number of Participants With at Least One Adverse Event
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. Treatment-Emergent adverse events (TEAEs) are defined as events with an onset date on or after the date of first dose of study treatment in the core study and ongoing at LTE study entry, or occurring during LTE study.
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score
The C-SSRS assesses the suicidal behavior and suicidal ideation in participants. Occurrence of suicidal behavior after study entry is defined as having answered "yes" to a least 1 of the 4 suicidal behavior subcategories (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). Occurrence of suicidal ideation is defined as having answered "yes" to at least 1 of the suicidal ideation sub-categories (1) wish to be dead, (2) nonspecific active suicidal thoughts, (3) active suicidal ideation with any methods (no plan) without intent to act, (4) active suicidal ideation with some intent to act (without specific plan), and (5) active suicidal ideation with specific plan and intent).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02070978
Brief Title
Long-term Safety and Tolerability of Atacicept (Long-term Follow-Up of Participant Who Participated in ADDRESS II)
Official Title
A Phase IIb, Multi-Center, Long-Term Extension Trial to Evaluate the Safety and Tolerability of Atacicept in Subjects With Systemic Lupus Erythematosus (SLE) Who Completed Protocol EMR-700461-023 (ADDRESS II)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated early due to shortage of drug supply.
Study Start Date
July 29, 2014 (Actual)
Primary Completion Date
April 5, 2016 (Actual)
Study Completion Date
February 9, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EMD Serono
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a multicenter, double-blind, Phase 2b, long-term extension (LTE) to the ADDRESS II core trial (EMR 700461-023) (NCT01972568), to evaluate long-term safety and tolerability of atacicept in participants with systemic lupus erythematosus (SLE). Participants who completed the 24-week core study ADDRESS II core study (NCT01972568) and thus not met any of the discontinuation criteria were invited to enter this long-term extension (LTE) study NCT02070978.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Erythematosus, Systemic
Keywords
Lupus Erythematosus, Systemic, Atacicept 75 and 150 mg, LTE
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Non-Randomized
Enrollment
253 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Atacicept 75 mg
Arm Type
Experimental
Arm Title
Atacicept 150 mg
Arm Type
Experimental
Arm Title
Placebo/Atacicept 150 mg
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Atacicept 75 mg
Intervention Description
Participants who received atacicept 75 milligram (mg) as once-weekly subcutaneous injection in the core study ADDRESS II continued to receive this dose during this LTE study. Participants in this reporting arm received the medication up to a maximum of 143.7 weeks.
Intervention Type
Drug
Intervention Name(s)
Atacicept 150 mg
Intervention Description
Participants who received placebo in the core study ADDRESS II switched to receive atacicept 150 mg as once-weekly subcutaneous injection for up to a maximum of 97.7 weeks during this LTE study.
Intervention Type
Drug
Intervention Name(s)
Atacicept 150 mg
Intervention Description
Participants who received atacicept 150 mg in core study ADDRESS II continued to receive atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Primary Outcome Measure Information:
Title
Number of Participants With at Least One Serious Adverse Event (SAE) During the Treatment Period
Description
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. Treatment- Emergent adverse events (TEAEs) during the treatment period exclude those ongoing at the time of study entry into 024 LTE Day 1 and exclude the safety follow-up period.
Time Frame
Baseline (LTE Day 1) up to maximum treatment duration of 143.7 weeks
Title
Number of Participants Who Prematurely Discontinued the Treatment Due to Adverse Event (AE)
Description
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. TEAEs were defined as events with an onset date on or after the date of first dose of study treatment in the core study and ongoing at the 024 LTE study entry, occurring during the 024 LTE study and the Safety follow-up Period.
Time Frame
Baseline (Day 1 of Core study) up to maximum duration of 167.7 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Organ Damage Scores
Description
SLICC/ACR score or damage index evaluates cumulative damage in Systemic Lupus Erythematosus (SLE). These changes may or may not be related to SLE. Most items are scored only if they have been present for at least 6 months. Scores range from 0 to 47 points, with higher scores indicating greater cumulative damage. Baseline was defined as Day 1 of Core study.
Time Frame
Baseline: Day 1 (Core Study), Day 1 (LTE Study), Week 24, Week 48, Week 72 and Week 96
Title
Change From Baseline in Disease Activity as Measured by British Isles Lupus Assessment Group (BILAG) 2004 Score
Description
BILAG Disease Activity Index evaluates systemic lupus erythematosus (SLE) activity in 8 organ system domains: General, mucocutaneous, neurological, musculoskeletal, cardiorespiratory, vasculitis, renal, and hematologic using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Severe disease activity; BILAG B: moderate disease activity; BILAG C: mild disease; BILAG D: system previously affected but now inactive; BILAG E: system never involved. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). The total BILAG score is the sum of the scores of the 8 domains where A=9, B=3, C=1, D=0, and E=0. The total score ranges from 0 to 72 with a higher score indicating greater lupus activity.
Time Frame
Baseline: Core study Screening, LTE Day 1, Week 24, Week 48, Week 72 and Week 96
Title
Change From Baseline in Disease Activity as Measured by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score
Description
SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms). Baseline was defined as core study screening visit.
Time Frame
Baseline: Screening Visit (Core Study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96
Title
Change From Baseline in Disease Activity as Measured by SLEDAI-2K Responder Index-50 (SRI-50) Score
Description
SRI-50 index was derived from SLEDAI-2K and could capture 50% or better improvement in each descriptor between any 2 visits in systemic lupus erythematosus (SLE) participants when there was incomplete resolution. The new assigned scores for the descriptors of SRI-50 were derived by dividing the score of each SLEDAI-2K descriptor by 2. SLEDAI-2K was an activity index that measured disease activity and records feature of active lupus as present or not present. SLEDAI-2K used a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present was assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranged from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Time Frame
Baseline: Screening Visit (Core Study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96
Title
Change From Baseline in Disease Activity as Measured by Physician's Global Assessment (PGA) Score
Description
The PGA was used to quantify disease activity and was measured using an anchored visual analog scale (VAS). The participant's current disease activity assessed by investigator in the score range of 0 to 3. Where 0=none; 1=mild; 2=moderate; 3=severe. The assessment made relative not to the participant's most severe state, but the most severe state of systemic lupus erythematosus (SLE) per the investigator's assessment. Baseline was defined as core study screening visit.
Time Frame
Baseline: Screening Visit (Core Study); LTE Day1, Week 24, Week 48, Week 72 and Week 96
Title
Number of Participants Who Achieved SLE Responder Index (SRI-4) Response (a Disease Activity Composite Index)
Description
SRI-4 response was defined as greater than or equal to 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline Physician's Global Assessment of Disease Activity (PGA). SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).
Time Frame
Baseline: Core study Screening; LTE Day 1, Week 24, Week 48, Week 72 and Week 96
Title
Number of Participants Who Achieved BILAG-based Combined Lupus Assessment (BICLA) Response (a Disease Activity Composite Index)
Description
The BICLA response was defined as BILAG-2004 improvement (all screening visit BILAG A improving to B/C/D, all screening visit BILAG B to C/D, and less than or equal to (<=1) new BILAG B and no new BILAG A); no deterioration in SLEDAI total score; PGA increase by less than (<) 0 percentage (%) (defined as less then (<)0.3 point increase for the statistical analyses) and no non-permitted medication/treatment. Baseline was defined as core study screening visit.
Time Frame
Baseline: Core study Screening; LTE Day 1, Week 24, Week 48, Week 72 and Week 96
Title
Percent Change From Baseline in Prednisone-equivalent Corticosteroid Dose
Time Frame
Baseline: Screening Visit (Core Study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96
Title
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score
Description
The 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) is based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100=highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100=highest level of physical functioning).
Time Frame
Baseline (Core Study Day 1); LTE Day 1, Week 24, Week 48, Week 72 and Week 96
Title
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score
Description
The LupusQoL was a lupus-specific health related QoL (HRQoL) questionnaire consisting of 34 items grouped in 8 domains: physical health, pain, planning, intimate relationships, burden to others, emotional health, body image, and fatigue. Participants indicate their responses on a 5-point Likert response format, where 4 = never, 3 = occasionally, 2 = a good bit of the time, 1 = most of the time, and 0 = all of the time. Summary scores can be calculated for all 8 domains. A LupusQoL score for each domain was reported on a 0 to 100 scale, with greater values indicating better HRQoL. Baseline was defined as Day 1 of core study.
Time Frame
Baseline (Core Study Day 1); LTE Day 1, Week 24, Week 48, Week 72, and Week 96
Title
Number of Participants With Patient Global Impression of Change (PGIC)
Description
The PGIC is self-rated scale that asks the participant to describe the change in activity limitations, symptoms, emotions, and overall Quality of life (QoL) related to the participant's painful condition on the following scale: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse) and 7 (very much worse). Number of participants in the PGIC categories of very much improved (1) and much improved (2) are reported.
Time Frame
Baseline (Core Study Day 1); LTE Day 1, Week 24, Week 48, Week 72 and Week 96
Title
Change From Baseline in EuroQoL 5 Dimension Instrument (EQ-5D) Score
Description
EQ-5D questionnaire comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels; 1=no problem, 2=moderate problems, 3=extreme problems. This part, called the EQ-5D descriptive system, provides a 5-dimensional description of health status. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state. Baseline was defined as Day 1 of Core study.
Time Frame
Baseline: Day 1 (Core Study), LTE Day 1, Week 24, Week 48, Week 72 and Week 96
Title
Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores
Description
EQ-5D is a participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 millimeters (mm) (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. Baseline defined as Day 1 of core study.
Time Frame
Baseline: Day 1 (Core Study), LTE Day 1, Week 24, Week 48, Week 72 and Week 96
Title
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score
Description
The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.
Time Frame
Baseline: Day 1 (Core study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96
Title
Number of Participants With at Least One Adverse Event
Description
An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. Treatment-Emergent adverse events (TEAEs) are defined as events with an onset date on or after the date of first dose of study treatment in the core study and ongoing at LTE study entry, or occurring during LTE study.
Time Frame
Baseline (Day 1 of Core study) up to maximum duration of 167.7 weeks
Title
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score
Description
The C-SSRS assesses the suicidal behavior and suicidal ideation in participants. Occurrence of suicidal behavior after study entry is defined as having answered "yes" to a least 1 of the 4 suicidal behavior subcategories (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). Occurrence of suicidal ideation is defined as having answered "yes" to at least 1 of the suicidal ideation sub-categories (1) wish to be dead, (2) nonspecific active suicidal thoughts, (3) active suicidal ideation with any methods (no plan) without intent to act, (4) active suicidal ideation with some intent to act (without specific plan), and (5) active suicidal ideation with specific plan and intent).
Time Frame
LTE Day 1, Week 24, Week 48, Week 72 and Week 98
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants who had completed the 24-week treatment period of study EMR-700461-023 (ADDRESS II core trial)
Women of childbearing potential who had a negative pregnancy test
Other protocol defined inclusion criteria were applied
Exclusion Criteria:
Active neurological symptoms of SLE that were deemed severe or progressive
Diagnosis of any demyelinating disease, such as, but not restricted to, multiple sclerosis (MS) or optic neuritis
Pregnancy
Active clinically significant viral, bacterial, or fungal infection, or any major episode of infection that in the investigator's opinion makes the participants unsuitable to continued participation in the study
Other protocol defined exclusion criteria were applied
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Pinnacle Research Group LLC
City
Anniston
State/Province
Alabama
ZIP/Postal Code
36207
Country
United States
Facility Name
University of Alabama at Birmingham - (UAB)
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Wallace Rheumatic Study Center
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Southern California Permenent Medical Group
City
Fontana
State/Province
California
ZIP/Postal Code
92335
Country
United States
Facility Name
East Bay Rheumatology Medical Group, Inc.
City
San Leandro
State/Province
California
ZIP/Postal Code
94578
Country
United States
Facility Name
Clinical Research of West Florida - Corporate
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33765
Country
United States
Facility Name
Clinical Research of West Florida, Inc.
City
Tampa
State/Province
Florida
ZIP/Postal Code
33603
Country
United States
Facility Name
McIlwain Medical Group, PA
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
AA MRC LLC Ahmed Arif Medical Research Center
City
Grand Blanc
State/Province
Michigan
ZIP/Postal Code
48439
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Clayton Medical Associates, P.C.
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63117
Country
United States
Facility Name
Rutgers New Jersey Medical School
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
The Feinstein Institute for Medical Research
City
Manhasset
State/Province
New York
ZIP/Postal Code
11031
Country
United States
Facility Name
Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
DJL Clinical Research, PLLC
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28210
Country
United States
Facility Name
MetroHealth System
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Arthritis & Rheumatology Center of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
Facility Name
OMRF
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Clinical Research Center of Reading LLC
City
Wyomissing
State/Province
Pennsylvania
ZIP/Postal Code
19610
Country
United States
Facility Name
Medical University of South Carolina (MUSC)
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Austin Regional Clinic, P.A.
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
Facility Name
Little River Arthritis & Osteoporosis Clinic
City
Waco
State/Province
Texas
ZIP/Postal Code
76708
Country
United States
Facility Name
Instituto CAICI
City
Rosario
State/Province
Santa Fe
ZIP/Postal Code
S2000PBJ
Country
Argentina
Facility Name
Centro Medico Privado de Reumatologia
City
San Miguel de Tucuman
State/Province
Tucuman
ZIP/Postal Code
T4000AXL
Country
Argentina
Facility Name
Investigaciones Clinicas Tucuman
City
San Miguel de Tucuman
State/Province
Tucuman
ZIP/Postal Code
T4000ICL
Country
Argentina
Facility Name
Centro Integral de Reumatologia
City
San Miguel de Tucumán
State/Province
Tucuman
ZIP/Postal Code
T4000DVB
Country
Argentina
Facility Name
Organizacion Medica de Investigacion (OMI)
City
Ciudad Autonoma Buenos Aires
ZIP/Postal Code
C1015ABO
Country
Argentina
Facility Name
APRILLUS
City
Ciudad Autonoma Buenos aires
ZIP/Postal Code
C1046AAQ
Country
Argentina
Facility Name
Atencion Integral en Reumatologia (AIR)
City
Ciudad Autonoma Buenos Aires
ZIP/Postal Code
C1426AAL
Country
Argentina
Facility Name
Hospital Privado Centro Medico de Cordoba
City
Cordoba
ZIP/Postal Code
X5016KEH
Country
Argentina
Facility Name
Cordis S.A.
City
Salta
ZIP/Postal Code
A4400ANW
Country
Argentina
Facility Name
Centro Polivalente de Asistencia e Inv. Clinica CER
City
San Juan
ZIP/Postal Code
5400
Country
Argentina
Facility Name
Centro de Pesquisas em Diabetes Ltda.
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035-170
Country
Brazil
Facility Name
MHAT "Eurohospital" - Plovdiv, OOD
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
Medical Center "Teodora", EOOD
City
Ruse
ZIP/Postal Code
7000
Country
Bulgaria
Facility Name
MHAT - Ruse, AD
City
Ruse
ZIP/Postal Code
7002
Country
Bulgaria
Facility Name
UMHAT "Sv. Ivan Rilski", EAD
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
DCC "Sveta Anna", EOOD
City
Sofia
ZIP/Postal Code
1750
Country
Bulgaria
Facility Name
Medical Center "Nov Rehabilitatsionen Tsentar", EOOD
City
Stara Zagora
ZIP/Postal Code
6000
Country
Bulgaria
Facility Name
MHAT-Targovishte, AD
City
Targovishte
ZIP/Postal Code
7700
Country
Bulgaria
Facility Name
Corporacion de Beneficencia Osorno
City
Osorno
ZIP/Postal Code
5290000
Country
Chile
Facility Name
Quantum Research Santiago
City
Puerto Varas
ZIP/Postal Code
5550170
Country
Chile
Facility Name
Centro Medico Prosalud
City
Santiago
ZIP/Postal Code
7500000
Country
Chile
Facility Name
Biomedica
City
Santiago
ZIP/Postal Code
7500710
Country
Chile
Facility Name
Centro de Estudios Reumatologicos
City
Santiago
ZIP/Postal Code
7501126
Country
Chile
Facility Name
CINVEC - Centro de Investigacion Clinica V Region
City
Viña del Mar
Country
Chile
Facility Name
Revmatologicky Ustav
City
Praha 2
ZIP/Postal Code
128 50
Country
Czechia
Facility Name
Revmatologicka ambulance
City
Uherske Hradiste
ZIP/Postal Code
686 01
Country
Czechia
Facility Name
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
City
Mainz
State/Province
Rheinland Pfalz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
City
Milano
ZIP/Postal Code
20122
Country
Italy
Facility Name
Seoul National University Hospital
City
Seoul
State/Province
Gyeonggi-do
ZIP/Postal Code
110744
Country
Korea, Republic of
Facility Name
Ajou University Hospital
City
Suwon-si
State/Province
Gyeonggi-do
ZIP/Postal Code
16499
Country
Korea, Republic of
Facility Name
Konkuk University Medical Center
City
Seoul
ZIP/Postal Code
05030
Country
Korea, Republic of
Facility Name
Hospital Universitario de Saltillo "Dr. Gonzalo Valdés Valdés"
City
Saltillo
State/Province
Coahuila
ZIP/Postal Code
25000
Country
Mexico
Facility Name
Clinstile, S.A. de C.V.
City
Mexico
State/Province
Distrito Federal
ZIP/Postal Code
06700
Country
Mexico
Facility Name
Morales Vargas Centro de Investigacion, S.C.
City
Leon
State/Province
Guanajuato
ZIP/Postal Code
37000
Country
Mexico
Facility Name
Icle S.C.
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44600
Country
Mexico
Facility Name
Unidad de Investigacion en Enfermedades Cronico Degenerativas SC
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44620
Country
Mexico
Facility Name
Clinica de Enfermedades Cronicas y de Procedimientos Especiales, S.C.
City
Morelia
State/Province
Michoacán
ZIP/Postal Code
58249
Country
Mexico
Facility Name
Accelerium S. de R.L. de C.V.
City
Monterrey
State/Province
Nuevo León
ZIP/Postal Code
64000
Country
Mexico
Facility Name
Centro Multidisciplinario para el desarrollo Especializado de la Investigacion Clinica en Yucatan
City
Merida
State/Province
Yucatán
ZIP/Postal Code
97130
Country
Mexico
Facility Name
Investigacion y Biomedicina de Chihuahua, S.C.
City
Chihuahua
ZIP/Postal Code
31000
Country
Mexico
Facility Name
Hogar Clínica San Juan de Dios - Arequipa
City
Arequipa
ZIP/Postal Code
00000
Country
Peru
Facility Name
Clinica Medica Cayetano Heredia
City
Lima
ZIP/Postal Code
Lima 31
Country
Peru
Facility Name
Invest Clinicas Sac Inst de Ginecologia y Reproduccion
City
Lima
ZIP/Postal Code
Lima 33
Country
Peru
Facility Name
Angeles University Foundation Medical Center
City
Angeles City, Pampanga
ZIP/Postal Code
2009
Country
Philippines
Facility Name
Mary Mediatrix Medical Center
City
Batangas
ZIP/Postal Code
4127
Country
Philippines
Facility Name
Davao Doctors Hospital
City
Davao
ZIP/Postal Code
8000
Country
Philippines
Facility Name
Iloilo Doctors Hospital
City
Iloilo
ZIP/Postal Code
5000
Country
Philippines
Facility Name
Szpital Uniwersytecki nr 2 im.dr J. Biziela
City
Bydgoszcz
ZIP/Postal Code
85-168
Country
Poland
Facility Name
FSBEI HE " First Moscow State Medical University n.a. I.M. Sechenov" of the MoH of the RF
City
Moscow
ZIP/Postal Code
119992
Country
Russian Federation
Facility Name
SBIH of Republic Kareliya "Republican Hospital n.a. V.A. Baranov"
City
Petrozavodsk
ZIP/Postal Code
185019
Country
Russian Federation
Facility Name
SPb SBIH "Clinical Rheumatological Hospital # 25"
City
Saint-Petersburg
ZIP/Postal Code
190068
Country
Russian Federation
Facility Name
SIH "Saratov City Clinical Hospital # 12"
City
Saratov
ZIP/Postal Code
410039
Country
Russian Federation
Facility Name
SBIH of Vladimir region "Regional Clinical Hospital"
City
Vladimir
ZIP/Postal Code
600023
Country
Russian Federation
Facility Name
SBHI of Yaroslavl Region "Clinical Hospital # 8"
City
Yaroslavl
ZIP/Postal Code
150003
Country
Russian Federation
Facility Name
Naidoo, A
City
Durban
State/Province
KwaZulu-Natal
ZIP/Postal Code
4319
Country
South Africa
Facility Name
Winelands Medical Research Centre
City
Stellenbosch
State/Province
Western Cape
ZIP/Postal Code
7600
Country
South Africa
Facility Name
Hospital Clinico Universitario de Valladolid
City
Valladolid
ZIP/Postal Code
47005
Country
Spain
Facility Name
Queen's Hospital
City
Romford
State/Province
Essex
ZIP/Postal Code
RM7 0AG
Country
United Kingdom
Facility Name
University College London Hospitals
City
London
State/Province
Greater London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
Guy's Hospital
City
London
State/Province
Greater London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
33547784
Citation
Wallace DJ, Isenberg DA, Morand EF, Vazquez-Mateo C, Kao AH, Aydemir A, Pudota K, Ona V, Aranow C, Merrill JT. Safety and clinical activity of atacicept in the long-term extension of the phase 2b ADDRESS II study in systemic lupus erythematosus. Rheumatology (Oxford). 2021 Nov 3;60(11):5379-5389. doi: 10.1093/rheumatology/keab115.
Results Reference
derived
Learn more about this trial
Long-term Safety and Tolerability of Atacicept (Long-term Follow-Up of Participant Who Participated in ADDRESS II)
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