A Phase IIIb Study of BMS-188667 in Subjects With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate

NCT00420199 | Completed Phase 3 Results

• 2 other identifiers: IM101-119Eudract: 2006-003768-67
• Study Type: interventional
• Target: 50
• Locations: 6 countries
• Sites: 10

Brief Summary

The only trial in participants who are methotrexate-inadequate responders and have active Rheumatoid Arthritis, in which gadolinium-enhanced Magnetic Resonance Imaging; Bone Mineral Density; and biochemical markers of bone, cartilage, and synovial tissue metabolism are used to evaluate early effects (4 months) of Abatacept on inflammation/structural damage. Study will provide valuable mechanism-of-action information on how Abatacept exerts its effects (including on bone) through new techniques.

Conditions

Active Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

• Double-blind Period: Mean Synovitis Scores at Baseline As Measured by the Rheumatoid Arthritis Clinical Trials 6 (OMERACT 6) Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS)

  Wrist synovitis was assessed by postgadolinium MRI enhancement according to OMERACT 6 RAMRIS in 3 wrist regions: distal radioulnar, radiocarpal, and intercarpal and carpometacarpal joints. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3\*3 wrist regions), indicating most severe damage. Change in synovitis = Follow-up synovitis score - baseline score.

  At baseline

• Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Planned Analysis Using Non-Parametric ANCOVA

  Wrist synovitis was assessed by postgadolinium MRI enhancement according to OMERACT 6 RAMRIS in 3 wrist regions: distal radioulnar, radiocarpal, and intercarpal and carpometacarpal joints. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3\*3 wrist regions), indicating most severe damage. Change in synovitis=Follow-up synovitis score-baseline score.

  Baseline to Day 113

• Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Post Hoc Sensitivity Analysis Using Parametric ANCOVA Analysis

  Wrist synovitis was assessed by postgadolinium MRI enhancement according to OMERACT 6 RAMRIS in 3 wrist regions: distal radioulnar, radiocarpal, and intercarpal and carpometacarpal joints. For each wrist region, possible score ranges from 0-3, with 0=normal, 1=mild, 2=moderate, and 3=severe damage. The total synovitis score per wrist=the sum of the individual scores for the 3 wrist regions. Minimum score per wrist ranges from 0, indicating no damage, to 9 (score of 3\*3 wrist regions), indicating most severe damage. Change in synovitis score=Follow-up synovitis score-baseline synovitis score.

  Baseline to Day 113

Secondary Outcomes (22)

• Double-blind Period: Baseline Mean Erosion OMERACT 6 Scores

  At baseline

• Double-blind Period: Adjusted Mean Change From Baseline in Erosion OMERACT 6 Scores

  Baseline to Day 113

• Double-blind Period: Baseline Mean Osteitis OMERACT 6 Scores

  At baseline

• Double-blind Period: Adjusted Mean Change From Baseline in Osteitis OMERACT 6 Scores

  Baseline to Day 113

• Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis

  Baseline to Day 113

Study Arms (2)

Abatacept + Methotrexate (Double-blind period)

ACTIVE COMPARATOR

Drug: Abatacept

Placebo + Methotrexate (Double-blind period)

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Abatacept DRUG

Vials (250 mg/vial), intravenous (IV), 10 mg/kg, monthly infusion , 12 months of treatment

Also known as: (BMS-188667), Orencia

Abatacept + Methotrexate (Double-blind period)

Placebo DRUG

Intravenous (IV) bags, IV, 0 mg, monthly infusion, 12 months of treatment

Placebo + Methotrexate (Double-blind period)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease activity as defined by a Disease Activity Score 28-C-Reactive Protein (CRP) \>3.2 or \>6 swollen and ≥6 tender joints and CRP greater than the upper limit of normal
• At least 1 erosion in hands/wrists or positive anticyclic citrullinated peptides or rheumatoid factor
• Clinically detectable synovitis of at least 1 wrist/ankle at screening and baseline
• Participants must have been treated with methotrexate, on a weekly dose of at least 15 mg or a maximum tolerated dose (such as, 10 mg weekly) for at least 3 months before screening. Dose of methotrexate must be stable for at least 28 days prior to the first study dose (Day 1)

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (10)

Local Institution

Brussels, 1200, Belgium

Location

Local Institution

Yvoir, 5530, Belgium

Location

Local Institution

Berlin, 14059, Germany

Location

Local Institution

Berlin, BE-10117, Germany

Location

Local Institution

Amsterdam, 1105 AZ, Netherlands

Location

Local Institution

Barcelona, 08036, Spain

Location

Local Institution

Barcelona, 08907, Spain

Location

Local Institution

Stockholm, 171 76, Sweden

Location

Local Institution

London, Greater London, SE19RT, United Kingdom

Location

Local Institution

Leeds, North Yorkshire, LS7 4SA, United Kingdom

Location

Related Publications (1)

• Conaghan PG, Durez P, Alten RE, Burmester GR, Tak PP, Klareskog L, Catrina AI, DiCarlo J, Gaillez C, Le Bars M, Zhou X, Peterfy C. Impact of intravenous abatacept on synovitis, osteitis and structural damage in patients with rheumatoid arthritis and an inadequate response to methotrexate: the ASSET randomised controlled trial. Ann Rheum Dis. 2013 Aug;72(8):1287-94. doi: 10.1136/annrheumdis-2012-201611. Epub 2012 Aug 21.

  PMID: 22915624 DERIVED

Related Links

• Investigator Inquiry form

MeSH Terms

Interventions

Abatacept

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2007
• First Posted: January 9, 2007
• Study Start: May 1, 2007
• Primary Completion: August 1, 2009
• Study Completion: May 1, 2010
• Last Updated: January 18, 2012
• Results First Posted: May 17, 2011

Record last verified: 2012-01

Locations

SE (1); ES (2); BE (2); GB (2); NL (1); DE (2)