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

This study has been completed.
Sponsor:
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00595413
First received: January 7, 2008
Last updated: January 19, 2016
Last verified: January 2016
  Purpose
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.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: Placebo matched to atacicept
Drug: Atacicept: with loading dose
Drug: Atacicept
Biological: Adalimumab
Phase 2

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

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Percentage of Participants Achieving American College of Rheumatology 50 Response Based on CRP (ACR50-CRP) at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants Achieving American College of Rheumatology 70 Response Based on CRP (ACR70-CRP) at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs [ Time Frame: From the first dose of study drug up to 30 days after the last dose of study drug, assessed up to Week 38 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 311
Study Start Date: September 2007
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atacicept 150 mg with loading dose Drug: 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.
Experimental: Atacicept 150 mg without loading dose Drug: Atacicept
Atacicept will be administered subcutaneously at a dose of 150 mg once a week for 25 weeks.
Active Comparator: Adalimumab Biological: Adalimumab
Adalimumab (Humira®) will be administered subcutaneously at a dose of 40 mg every other week for 25 weeks.
Other Name: Humira®
Placebo Comparator: Placebo 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00595413

Locations
United States, Massachusetts
Please Contact US Medical Information
Rockland, Massachusetts, United States
Germany
Please contact the Merck KGaA Communication Center
Darmstadt, Germany
Sponsors and Collaborators
EMD Serono
Merck KGaA
Investigators
Study Director: Medical Responsible Merck Serono International SA, an affiliate of Merck KGaA Darmstadt, Germany
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00595413     History of Changes
Other Study ID Numbers: 27905  2007-002536-29 
Study First Received: January 7, 2008
Results First Received: January 19, 2016
Last Updated: January 19, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by EMD Serono:
Rheumatoid arthritis
Atacicept
Adalimumab
Humira®

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on December 07, 2016