Clinical trial NCT00430495: A Phase 2 Dose-finding Study of Atacicept in Subjects With Rheumatoid Arthritis (AUGUST I)
Official title: A Randomized, Double-blind, Placebo-controlled, Multicentre, Phase II Dose-finding Study of Atacicept Given Subcutaneously in Subjects With Rheumatoid Arthritis and Inadequate Response to TNFa Antagonist Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: atacicept
arthritis
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2007-02-02
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a double-blind, placebo-controlled, parallel-arm, multicentre, prospective dose-finding trial of the safety and efficacy of atacicept in subjects with active rheumatoid arthritis who had failed a three month therapeutic trial with a tumor necrosis factor alpha (TNFa) antagonist due to lack of efficacy.


Eligibility criteria: Inclusion Criteria:

1. Rheumatoid arthritis (RA) satisfying American College of Rheumatology (ACR) diagnostic criteria with a disease history of at least one year
2. Male or female greater than or equal to (\>=)18-years of age at time of informed consent
3. Active RA as defined by:

   * \>=8 swollen joints (66-joint count),
   * \>=8 tender joints (68-joint count), and
   * C-reactive protein (CRP) \>=10 milligram per liter (mg/L) (central laboratory) and/or erythrocyte sedimentation rate (ESR) \>= to 28 millimeter per hour (mm/h)
4. Failure of at least one TNFa antagonist therapy (previously or at the time of screening) as specified in the protocol
5. Other protocol defined inclusion criteria could apply

Exclusion Criteria:

1. Any condition, including laboratory findings or findings in the medical history or pre-trial assessments, that in the opinion of the Investigator constitutes a risk or a contraindication for the subject's participation in the trial or that could interfere with the trial objectives, conduct or evaluation
2. Treatment with biologics aiming at B cell modulation such as rituximab or belimumab within 2 years before study Day 1
3. Any previous treatment with anakinra (Kineret), abatacept (Orencia) or tocilizumab within 3 months before study Day 1
4. Use of etanercept (Enbrel) within 28 days before study Day 1, or of infliximab (Remicade) or adalimumab (Humira) within 60 days before study Day 1
5. Participation in any interventional clinical trial with an unapproved investigational therapy within the 3 months before the start of this study (or within 5 half-lives of the investigated compound before study Day 1, whichever is longer)
6. Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26
timeFrame: Week 26
Secondary outcomes:
measure: Percentage of Participants Achieving American College of Rheumatology 50 Response Based on CRP (ACR50-CRP) at Week 26
timeFrame: Week 26
measure: Percentage of Participants Achieving American College of Rheumatology 70 Response Based on CRP (ACR70-CRP) at Week 26
timeFrame: Week 26
measure: Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of Less Than or Equal to (<=) 3.2 at Week 26
timeFrame: Week 26
measure: Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of <=2.6 at Week 26
timeFrame: Week 26
measure: Percentage of Participants Achieving Improvement in Health Assessment Questionnaire Disability Index (HAQ-DI) of at Least 0.3 From Baseline at Week 26
timeFrame: Week 26
measure: Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 26
timeFrame: Week 26
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 38
Other outcomes:
Locations:
city: Rockland
country: United States
facility: EMD Serono
state: Massachusetts
city: Canada
country: Canada
facility: Merck/Serono
Study officials:
affiliation: EMD Serono, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Genovese MC, Kinnman N, de La Bourdonnaye G, Pena Rossi C, Tak PP. Atacicept in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor antagonist therapy: results of a phase II, randomized, placebo-controlled, dose-finding trial. Arthritis Rheum. 2011 Jul;63(7):1793-803. doi: 10.1002/art.30373.