Atacicept Phase 2/3 in Generalized Systemic Lupus Erythematosus (APRIL-SLE)
- Conditions
- Lupus Erythematosus, Systemic
- Interventions
- Registration Number
- NCT00624338
- Lead Sponsor
- EMD Serono
- Brief Summary
This study is to evaluate the efficacy and safety of atacicept compared to placebo in preventing new flares in subjects with systemic lupus erythematosus (SLE) and to confirm the optimal dose of atacicept for treatment of subjects with SLE and gain information on the effect of atacicept on markers specific to its mechanism of action (MoA) and their correlation to disease activity/progression. Study medication will be administered through subcutaneous (under the skin) injections, beginning with twice weekly injections for the first 4 weeks, followed by once weekly doses for 48 weeks. Following the last treatment, a safety follow-up period of 24 weeks will be conducted.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 461
- Male or female 16 years of age or older
- Disease history of at least six months meeting at least 4 out of the 11 American College of Rheumatology (ACR) criteria for SLE
- Active SLE with at least one British Isles Lupus Assessment Group (BILAG) flare A or B at screening requiring a change in the dose of corticosteroids
- Positive antinuclear antibody (ANA) or anti-double-stranded deoxyribonucleic acid (dsDNA) at screening
- Female subjects must be willing to avoid pregnancy by using an adequate method of contraception for 4 weeks prior to Study Day 1, during the trial and 24 weeks after the last dose of study medication
- Other protocol defined inclusion criteria could apply
- Active moderate to severe glomerulonephritis (kidney impairment) as defined in the protocol
- Active central nervous system SLE deemed to be severe/progressive and/or associated with significant cognitive impairment leading to inability to provide informed consent and/or comply with the protocol
- Previous treatment with rituximab, abatacept, or belimumab
- History of demyelinating disease such as multiple sclerosis (MS) or optic neuritis
- Other protocol defined exclusion criteria could apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atacicept 75 mg Atacicept 75 mg - Placebo Placebo Comparator - Atacicept 150 mg Atacicept 150 mg -
- Primary Outcome Measures
Name Time Method Percentage of Participants Experiencing a New Flare as Defined by British Isles Lupus Assessment Group (BILAG) Score A or B From screening up to Week 52 A flare was defined as having an adjudicated BILAG A or B score in any of the 8 organ systems during treatment, or imputed for participants who had premature treatment discontinuation. Discontinuations due to sponsor termination of the atacicept 150 mg group were not imputed as flares in this analysis. The BILAG disease activity index evaluates systemic lupus erythematosus (SLE) activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease-modifying treatment (prednisone greater than 20 mg daily or immunosuppressants); BILAG B: Disease less active than in "A", mild reversible problems requiring only symptomatic therapy such as antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), or prednisone less than 20 mg day; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved.
- Secondary Outcome Measures
Name Time Method Time to First New Flare as Defined by BILAG Score A or B From screening up to Week 52 A flare was defined as having an adjudicated BILAG A or B score in any of the 8 organ systems during treatment. Analysis was right-censored at Week 52. The hazard ratios and 95% confidence intervals were obtained from the Cox proportional hazards model. The 25th Percentile of time to new flare was reported using Kaplan-Meier estimates (Median was not reached). The BILAG disease activity index evaluates SLE activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease-modifying treatment (prednisone greater than 20 mg daily or immunosuppressants); BILAG B: Disease less active than in "A", mild reversible problems requiring only symptomatic therapy such as antimalarials, NSAIDs, or prednisone less than 20 mg day; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved.
Percentage of Participants Within Ordinal Response Categories for British Isles Lupus Assessment Group (BILAG) Flares Week 52 Ordinal response categories have been defined as: 1) No BILAG A, no BILAG B, and completed treatment, 2) No BILAG A, at least 1 BILAG B during treatment period, and 3) At least 1 BILAG A during treatment period. The BILAG disease activity index evaluates SLE activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease-modifying treatment (prednisone greater than 20 mg daily or immunosuppressants); BILAG B: Disease less active than in "A", mild reversible problems requiring only symptomatic therapy such as antimalarials, NSAIDs, or prednisone less than 20 mg day; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved.
Percentage of Participants Experiencing a New Flare as Defined by BILAG Score A or B During Initial 24 Weeks From screening up to Week 24 A flare was defined as having an adjudicated BILAG A or B score in any of the 8 organ systems during treatment, or imputed for participants who had premature treatment discontinuation. The BILAG disease activity index evaluates SLE activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease-modifying treatment (prednisone greater than 20 mg daily or immunosuppressants); BILAG B: Disease less active than in "A", mild reversible problems requiring only symptomatic therapy such as antimalarials, NSAIDs, or prednisone less than 20 mg day; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved.
Mean Cumulative Corticosteroid Dose Randomization up to Week 52
Trial Locations
- Locations (13)
Justus J. Fiechtner, MD, MPH
🇺🇸Lansing, Michigan, United States
Inland Rheumatology Clinical Trials Inc
🇺🇸Upland, California, United States
Research Site
🇬🇧Manchester, United Kingdom
Stanford University
🇺🇸Palo Alto, California, United States
SUNY Health Science Center at Brooklyn
🇺🇸Brooklyn, New York, United States
Feinstein Institute for Medical Research
🇺🇸Manhasset, New York, United States
Hospital for Special Surgey
🇺🇸New York, New York, United States
US Local Medical Information
🇺🇸Rockland, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Division of Clinical Immunology and Rheumatology - UAB
🇺🇸Birmingham, Alabama, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
University of Cincinnati Medical Center, Division of Immunology
🇺🇸Cincinnati, Ohio, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States