Atacicept in Anti-Tumor Necrosis Factor Alpha-naïve Subjects With Rheumatoid Arthritis (AUGUST II)

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy of atacicept compared to placebo in the treatment of signs and symptoms in a subject population with active rheumatoid arthritis (RA), inadequate response to methotrexate (MTX) and no previous exposure to anti-tumor necrosis factor alpha (anti-TNFalpha) therapy.

Official Title
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A Randomised, Double-blind, Placebo Controlled, Multi-centre Phase II Study of Atacicept in Anti-TNFα-naïve Patients With Moderate to Severely Active Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Placebo matched to atacicept
* Drug: Atacicept: with loading dose
* Drug: Atacicept
* Biological: Adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects greater than or equal to (>=) 18 years of age at the time of informed consent who have RA satisfying American College of Rheumatology (ACR) criteria with a disease history of at least 6 months Subjects must have active disease, defined by >=8 swollen joints (out of 66), >=8 tender joints (out of 68) and CRP >=10 milligram per liter (mg/L) and/or erythrocyte sedimentation rate (ESR) >=28 millimeter per hour (mm/hr), despite treatment with MTX at a dose of >=15 milligram per week (mg/week) for greater than (>) 3 months Other protocol-defined inclusion criteria could apply Exclusion Criteria: Inflammatory joint disease other than RA Previous or concurrent treatment with any approved or investigational biological compound for RA, including but not restricted to any anti-TNFalpha agents, rituximab, abatacept, tocilizumab, interleukin-1 receptor antagonist (IL-1Ra) and belimumab Treatment with disease-modifying anti-rheumatic drug (DMARDs) other than MTX Participation in any interventional clinical trial within 1 month before study Day 1 MTX dose >25 mg/week, prednisone dose >10 mg/day (or equivalent), or change in steroid or non-steroidal anti-inflammatory drug (NSAID) dosing regimen within 28 days before study Day 1 Immunization with live vaccine or immunoglobulin (Ig) treatment within 28 days before study Day 1 or need for such treatment during the study (including follow-up) Any history or presence of active or latent tuberculosis, major infection requiring hospitalization or intravenous anti-infectives within 28 days before study Day 1 Other major concurrent illness or organ dysfunction as specified in the protocol Serum IgG below 6 gram per liter (g/L) Known hypersensitivity to atacicept or to any of the components of the formulated atacicept Other protocol-defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atacicept 150 mg with loading dose<br> | Drug: Atacicept: with loading dose<br>* Atacicept will be administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.<br>|
| Experimental: Atacicept 150 mg without loading dose<br> | Drug: Atacicept<br>* Atacicept will be administered subcutaneously at a dose of 150 mg once a week for 25 weeks.<br>|
| Active Comparator: Adalimumab<br> | Biological: Adalimumab<br>* Adalimumab (Humira®) will be administered subcutaneously at a dose of 40 mg every other week for 25 weeks.<br>* Other names: Humira®;|
| Placebo Comparator: Placebo<br> | Drug: Placebo matched to atacicept<br>* Placebo matched to atacicept will be administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26 | ACR20-CRP response is defined as greater than or equal to (>=) 20 percent (%) improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=20% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). | Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology 50 Response Based on CRP (ACR50-CRP) at Week 26 | ACR50-CRP response is defined as >=50% improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=50% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). | Week 26 | 
| Percentage of Participants Achieving American College of Rheumatology 70 Response Based on CRP (ACR70-CRP) at Week 26 | ACR70-CRP response is defined as >=70% improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=70% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). | Week 26 | 
| Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 26 | The EULAR response criteria evaluate change in DAS28 scores represented as good response, moderate response, or no response considering both the current DAS28 score and the observed improvement from baseline. Participants were considered to have good or moderate EULAR response if at the time of assessment, their DAS28 score was less than or equal to (<=) 5.1 and the improvement from baseline in their DAS28 score was greater than (>) 0.6; or if at the time of assessment, their DAS28 score was >5.1 and improvement from baseline in their DAS28 score was >1.2. | Week 26 | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. 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. | From the first dose of study drug up to 30 days after the last dose of study drug, assessed up to Week 38 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis, Atacicept, Adalimumab, Humira®