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

Rheumatoid Arthritis Clinical Trial

— AUGUST II  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00595413
• Other study ID #: 27905
• Secondary ID: 2007-002536-29
• Status: Completed
• Phase: Phase 2
• First received: January 7, 2008
• Last updated: January 19, 2016
• Start date: September 2007
• Est. completion date: October 2009

Study information

• Verified date: January 2016
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 311
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Placebo matched to atacicept
Placebo matched to atacicept will be administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.
• Atacicept: with loading dose
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.
• Atacicept
Atacicept will be administered subcutaneously at a dose of 150 mg once a week for 25 weeks.

Biological:
• Adalimumab
Adalimumab (Humira®) will be administered subcutaneously at a dose of 40 mg every other week for 25 weeks.

Locations

Country	Name	City	State
Germany	Please contact the Merck KGaA Communication Center	Darmstadt
United States	Please Contact US Medical Information	Rockland	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono	Merck KGaA

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes

External Links

•   The European League Against Rheumatism (EULAR)