Atacicept Phase 2/3 in Generalized Systemic Lupus Erythematosus (APRIL-SLE)

Study Overview
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Brief Summary
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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.

Official Title
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A Randomised, Double-blind, Placebo Controlled, Multicentre Prospective Dose-finding Phase II/III Study With Atacicept Given Subcutaneously to Subjects Having Recently Experienced a Flare of Systemic Lupus Erythematosus (SLE)

Conditions
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Lupus Erythematosus, Systemic

Intervention / Treatment
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* Drug: Atacicept 75 mg
* Drug: Atacicept 150 mg
* Other: Placebo Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atacicept 75 mg<br> | Drug: Atacicept 75 mg<br>* 75 milligram (mg) atacicept injection will be administered subcutaneously twice weekly during initial loading period for 4 weeks followed by once weekly during maintenance period for subsequent 48 weeks.<br>|
| Experimental: Atacicept 150 mg<br> | Drug: Atacicept 150 mg<br>* 150 mg atacicept injection will be administered subcutaneously twice weekly during initial loading period for 4 weeks followed by once weekly during maintenance period for subsequent 48 weeks.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo Comparator<br>* Placebo matched to atacicept injection will be administered subcutaneously twice weekly during initial loading period for 4 weeks followed by once weekly during maintenance period for subsequent 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing a New Flare as Defined by British Isles Lupus Assessment Group (BILAG) Score A or B | 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. | From screening up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First New Flare as Defined by BILAG Score A or B | 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. | From screening up to Week 52 | 
| Percentage of Participants Experiencing a New Flare as Defined by BILAG Score A or B During Initial 24 Weeks | 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. | From screening up to Week 24 | 
| Percentage of Participants Within Ordinal Response Categories for British Isles Lupus Assessment Group (BILAG) Flares | 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. | Week 52 | 
| Mean Cumulative Corticosteroid Dose |  | Randomization up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atacicept 75 and 150 mg, Placebo