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A Phase 2 Dose-finding Study of Atacicept in Subjects With Rheumatoid Arthritis (AUGUST I) (AUGUST I)

This study has been completed.
Sponsor:
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00430495
First received: January 30, 2007
Last updated: January 19, 2016
Last verified: January 2016
  Purpose
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.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: Atacicept
Drug: Placebo matched to atacicept
Phase 2

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

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 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 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 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 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 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 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 Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of Less Than or Equal to (<=) 3.2 at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100-millimeter (mm) visual analog scale (the participant's global assessment of disease activity). DAS28 ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission.

  • Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of <=2.6 at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100 mm visual analog scale (the participant's global assessment of disease activity). DAS28 ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission.

  • Percentage of Participants Achieving Improvement in Health Assessment Questionnaire Disability Index (HAQ-DI) of at Least 0.3 From Baseline at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    The HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item was scored on 4-point scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range is 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Percentage of participants achieving improvement in HAQ-DI of at least 0.3 from baseline at Week 26 was reported.

  • Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response 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 <=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 Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 38 ] [ Designated as safety issue: Yes ]
    An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An 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: 256
Study Start Date: December 2006
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atacicept 25 mg Drug: Atacicept
Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.
Experimental: Atacicept 75 mg Drug: Atacicept
Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 weeks.
Experimental: Atacicept 150 mg Drug: Atacicept
Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.
Placebo Comparator: Placebo Drug: Placebo matched to atacicept
Placebo matched to atacicept was 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:

  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
  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: NCT00430495

Locations
United States, Massachusetts
EMD Serono
Rockland, Massachusetts, United States, 02370
Canada
Merck/Serono
Canada, Canada
Sponsors and Collaborators
EMD Serono
Merck KGaA
Investigators
Study Director: Medical Responsible EMD Serono, an affiliate of Merck KGaA, Darmstadt, Germany
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00430495     History of Changes
Other Study ID Numbers: 27298 
Study First Received: January 30, 2007
Results First Received: January 19, 2016
Last Updated: January 19, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by EMD Serono:
atacicept
arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on December 09, 2016