Clinical trial NCT00420199: A Phase IIIb Study of BMS-188667 in Subjects With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Active Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-01-09
Enrollment: 50
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: 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.


Eligibility criteria: 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)

Primary outcomes:
measure: 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)
timeFrame: At baseline
measure: Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Planned Analysis Using Non-Parametric ANCOVA
timeFrame: Baseline to Day 113
measure: Double-blind Period: Mean Change From Baseline in OMERACT 6 Wrist Synovitis Score: Post Hoc Sensitivity Analysis Using Parametric ANCOVA Analysis
timeFrame: Baseline to Day 113
Secondary outcomes:
measure: Double-blind Period: Baseline Mean Erosion OMERACT 6 Scores
timeFrame: At baseline
measure: Double-blind Period: Adjusted Mean Change From Baseline in Erosion OMERACT 6 Scores
timeFrame: Baseline to Day 113
measure: Double-blind Period: Baseline Mean Osteitis OMERACT 6 Scores
timeFrame: At baseline
measure: Double-blind Period: Adjusted Mean Change From Baseline in Osteitis OMERACT 6 Scores
timeFrame: Baseline to Day 113
measure: Double-blind Period: Number of Participants With Newly Involved Joints in Bone Erosion, Edema/Osteitis, and Synovitis
timeFrame: Baseline to Day 113
measure: Double-blind Period: Baseline Mean RAMRIS Scores
timeFrame: Baseline
measure: Double-blind Period: Adjusted Mean Change From Baseline in RAMRIS Scores
timeFrame: Baseline to Day 113
measure: 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)
timeFrame: Baseline to Days 15, 29, 57, 85, and 113
measure: 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])
timeFrame: Baseline to Days 15, 29, 57, 85, and 113
measure: 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])
timeFrame: Baseline to Days 15, 29, 57, 85, and 113
measure: Double-blind Period: Median Percent Change From Baseline in Systemic Marker of Synovial Tissue Metabolism (Creatinine-corrected Urinary Glucosyl-Galactosyl-Pyridinoline [UGGPC])
timeFrame: Baseline to Days 15, 29, 57, 85, and 113
measure: 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
timeFrame: 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
measure: Double-blind Period: Number of Participants With AEs of Special Interest
timeFrame: 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
measure: Double-blind Period: Number of Participants With Infections/Infestations of Special Interest
timeFrame: 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
measure: Double-blind Period: Number of Participants With Acute Infusional AEs of Special Interest
timeFrame: 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
measure: Double-blind Period: Number of Participants With Peri-infusional AEs of Special Interest
timeFrame: 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
measure: Double-blind Period: Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality
timeFrame: 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
measure: Double-blind Period: Number of Participants With Laboratory Test Results for Liver and Kidney Function Meeting Criteria for Marked Abnormality
timeFrame: 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
measure: Double-blind Period: Number of Participants With Laboratory Test Results for Electrolytes Meeting the Criteria for Marked Abnormality
timeFrame: 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
measure: Double-blind Period: Number of Participants With Laboratory Test Results in Other Chemistries and Urinalysis Meeting the Criteria for Marked Abnormality
timeFrame: 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
measure: Double-blind Period:Number of Participants With Significantly Abnormal Changes in Vital Signs
timeFrame: Days 1, 15, 29, 57, 85, and 113
measure: Double-blind Period: Number of Participants With Positive Antibodies to Abatacept by Electrochemiluminescence (ECL) Assay
timeFrame: Day 1 to Day 113
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Local Institution
city: Yvoir
country: Belgium
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Amsterdam
country: Netherlands
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Stockholm
country: Sweden
facility: Local Institution
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Leeds
country: United Kingdom
facility: Local Institution
state: North Yorkshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.