A Phase IIIB Multicenter, Randomized, Double-Blind, Placebo-controlled Study to Assess Short-term Changes in Synovitis and Structural Damage Outcomes in Subjects With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate, Treated With Abatacept Versus Placebo on a Background Therapy With Methotrexate
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- 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)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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)
Exclusion Criteria
- Not provided
Arms & Interventions
Abatacept + Methotrexate (Double-blind period)
Intervention: Abatacept (Drug)
Placebo + Methotrexate (Double-blind period)
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
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)
Time Frame: At baseline
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.
Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Planned Analysis Using Non-Parametric ANCOVA
Time Frame: Baseline to Day 113
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.
Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Post Hoc Sensitivity Analysis Using Parametric ANCOVA Analysis
Time Frame: Baseline to Day 113
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.
Secondary Outcomes
- 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)
- Double-blind Period: Baseline Mean RAMRIS Scores(Baseline)
- Double-blind Period: Adjusted Mean Change From Baseline in RAMRIS Scores(Baseline to Day 113)
- Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Formation: Osteocalcin and Serum Intact N-terminal Propeptide of Type I Procollagen (PINP)(Baseline to Days 15, 29, 57, 85, and 113)
- Double-blind Period: Median Percent Change From Baseline in Systemic Markers of Bone Destruction (Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen [CTX-I] and Serum Pyridinoline Cross-linked Telopeptide Domain of Type I Collagen [ICTP])(Baseline to Days 15, 29, 57, 85, and 113)
- Double-blind Period: Median Percent Change From Baseline in a Systemic Marker of Cartilage Degradation (Creatinine-corrected Urinary Carboxyterminal Crosslinking Telopeptide of Type II Collagen [UCTX2C])(Baseline to Days 15, 29, 57, 85, and 113)
- Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC])(Baseline to Days 15, 29, 57, 85, and 113)
- Double-blind Period: Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation(From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period)
- Double-blind Period: Number of Participants With AEs of Special Interest(From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period)
- Double-blind Period: Number of Participants With Infections/Infestations of Special Interest(From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period)
- Double-blind Period: Number of Participants With Acute Infusional AEs of Special Interest(From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period)
- Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest(From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period)
- Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality(From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period)
- Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality(From Day 1 to Day 113, and including up to 56 days post last dose of double-blind period, or start of first dose of open-label period)
- Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality(From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period)
- Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality(From Day 1 to Day 113, and up to 56 days post last dose of double-blind period, or start of first dose of open-label period)
- Double-blind Period:Number of Participants With Significantly Abnormal Changes in Vital Signs(Days 1, 15, 29, 57, 85, and 113)
- Double-blind Period: Number of Participants With Positive Antibodies to Abatacept by Electrochemiluminescence (ECL) Assay(Day 1 to Day 113)