Phase IIB Rheumatoid Arthritis Dose Ranging Study for BMS-945429 in Subjects Who Are Not Responding to Methotrexate
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT01373151
- Lead Sponsor
- CSL Behring
- Brief Summary
The purpose of this study is to determine the effective dose of BMS-945429 in subjects with inadequate response to Methotrexate in the treatment of moderate to severe Rheumatoid Arthritis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 418
- Inadequate response to Methotrexate
- Must have been taking Methotrexate for at least 3 months at a minimal weekly dose of at least 15 mg and stable dose for 4 weeks prior to randomization
- American College of Rheumatology (ACR) global function status class 1-3
- Minimum of 6 swollen and 6 tender joints with evidence of synovitis in at least 1 hand or wrist
- High sensitivity C-reactive protein (hsCRP) ≥ 0.8 mg/dL
- Previously received or currently receiving concomitant biologic therapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2 BMS-945429 BMS-945429 + Methotrexate + Adalimumab Placebo Arm 1 Adalimumab Placebo BMS-945429 Placebo/BMS-945429+Methotrexate+Adalimumab Placebo Arm 1 BMS-945429 BMS-945429 Placebo/BMS-945429+Methotrexate+Adalimumab Placebo Arm 1 Methotrexate BMS-945429 Placebo/BMS-945429+Methotrexate+Adalimumab Placebo Arm 2 Methotrexate BMS-945429 + Methotrexate + Adalimumab Placebo Arm 2 Adalimumab Placebo BMS-945429 + Methotrexate + Adalimumab Placebo Arm 3 BMS-945429 BMS-945429 + Methotrexate + Adalimumab Placebo Arm 3 Methotrexate BMS-945429 + Methotrexate + Adalimumab Placebo Arm 3 Adalimumab Placebo BMS-945429 + Methotrexate + Adalimumab Placebo Arm 4 BMS-945429 BMS-945429 + Methotrexate + Adalimumab Placebo Arm 4 Methotrexate BMS-945429 + Methotrexate + Adalimumab Placebo Arm 4 Adalimumab Placebo BMS-945429 + Methotrexate + Adalimumab Placebo Arm 5 BMS-945429 BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo Arm 5 Methotrexate BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo Arm 6 BMS-945429 BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo Arm 6 Methotrexate BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo Arm 6 Adalimumab Placebo BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo Arm 7 Methotrexate Adalimumab + Methotrexate Arm 7 Adalimumab Adalimumab + Methotrexate Arm 5 Methotrexate Placebo BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo Arm 6 Methotrexate Placebo BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo Arm 1 BMS-945429 Placebo BMS-945429 Placebo/BMS-945429+Methotrexate+Adalimumab Placebo Arm 5 Adalimumab Placebo BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo
- Primary Outcome Measures
Name Time Method Percent of Participants Achieving an American College of Rheumatology (ACR) 20% Response Rate At 12 Weeks The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[most often Health Assessment Questionnaire (HAQ)\], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
- Secondary Outcome Measures
Name Time Method Percent of Participants Achieving ACR 50 Response Rate At weeks 12 and 24 The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[most often Health Assessment Questionnaire (HAQ)\], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
Percent of Participants Achieving ACR 70 Response Rate At weeks 12 and 24 The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[most often Health Assessment Questionnaire (HAQ)\], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
Percent of Participants With ACR 20 Response At 24 weeks The ACR20/50/70 is a composite measure defined as both improvement of 20%, 50% or 70% in the number of tender and number of swollen joints, and a 20%, 50% or 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[most often Health Assessment Questionnaire (HAQ)\], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
Mean Change From Baseline in Disease Activity as Measured by Disease Activity Score 28 C-reactive Protein (DAS28-CRP) Baseline, weeks 12 and 24 DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.
Percent of Participants With Remission by DAS28-CRP At weeks 12 and 24 DAS28-CRP = Disease Activity Scores 28 based on C Reactive Protein. A DAS28-CRP below 2.6 is interpreted as remission.
Mean Change From Baseline in Clinical Disease Activity Index (CDAI) Baseline, weeks 12 and 24 CDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (SCJ) (0-28) and tender joint count (TJC) (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity. The CDAI has a range from 0 to 76.
CDAI \<= 2.8 = Remission CDAI \> 2.8 and \<= 10 = Low Disease Activity CDAI \> 10 and \<= 22 = Moderate Disease Activity CDAI \> 22 = High Disease ActivityPercent of Participants With Remission by CDAI At weeks 12 and 24 CDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (SCJ) (0-28) and tender joint count (TJC) (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity. The CDAI has a range from 0 to 76.
CDAI \<= 2.8 = Remission CDAI \> 2.8 and \<= 10 = Low Disease Activity CDAI \> 10 and \<= 22 = Moderate Disease Activity CDAI \> 22 = High Disease ActivityMean Change From Baseline in Simplified Disease Activity Index (SDAI) Baseline, weeks 12 and 24 SDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (0-28) and tender joint count (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity and C-reactive protein (0-10). The SDAI has a range from 0 to 86.
0.0 - 3.3 = Remission 3.4 - 11.0 = Low Activity 11.1 - 26.0 = Moderate Activity 26.1 - 86.0 = High ActivityPercent of Participants With Remission by SDAI At weeks 12 and 24 SDAI is a composite index for assessing disease activity. CDAI is based on the simple summation of the count of swollen joint count (0-28) and tender joint count (0-28) along with patient global assessment (0-10) Scale and physician global assessment (0-10) for estimating disease activity where 10 means maximal activity and C-reactive protein (0-10). The SDAI has a range from 0 to 86.
0.0 - 3.3 = Remission 3.4 - 11.0 = Low Activity 11.1 - 26.0 = Moderate Activity 26.1 - 86.0 = High ActivityPercent of Participants With Remission Rate by Boolean Definition At weeks 12 and 24 Boolean-based definition:
At any time point, a patient must satisfy all of the following:
TJC ≤1 (0-28) SJC ≤1 (0-28) CRP ≤1 mg/dl Patient Global Assessment ≤1 (on a 0-10 scale)Mean Change From Baseline in Health Assessment Questionnaire (HAQ) Disability Index Baseline, weeks 12 and 24 Patients report the amount of difficulty they have in performing 8 categories. Each category is scored on a scale ranging from 0 (performed without any difficulty) to 3 (cannot be done at all). The HAQ-DI is then calculated by summing the scores and dividing by the number of categories answered. Total score is between 0-3.0. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment. The HAQ-DI cannot be calculated if the subject does not have scores for at least 6 categories. A response was defined as a subject with a reduction from baseline in HAQ-DI of at least 0.22.
Mean Change From Baseline in Short Form 36 (SF-36) as Measured by Physical and Mental Components Baseline, weeks 12 and 24 The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). To score the SF-36, scales are standardized with a scoring algorithm to obtain a score ranging from 0 to 100. Higher scores indicate better health status.
Mean Change From Baseline in Fatigue Severity (VAS) Score Baseline, weeks 12 and 24 A 9-item questionnaire with questions related to how fatigue interferes with certain activities and rates its severity according to a self-report scale. The items are scored on a 7 point scale with 1 = strongly disagree and 7= strongly agree. The minimum score = 9 and maximum score possible = 63. Higher the score = greater fatigue severity.
Mean Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Scores Baseline, weeks 12 and 24 The WPAI yeilds four types of scores:
1. Absenteeism (work time missed)
2. Presenteesism (impairment at work / reduced on-the-job effectiveness)
3. Work productivty loss (overall work impairment / absenteeism plus presenteeism)
4. Activity Impairment WPAI outcomes are expressed as impairment percentages with each subscale score ranging from 0-100. The subscale scores are added and averaged to produce a total WPAI score between 0-100. Higher scores indicate greater impairment and less productivity.Mean Change From Baseline in Radiographic (MRI) Progression of Synovitis, Osteitis (Bone Marrow Edema), Bone Erosion and Cartilage Loss (Joint-space Narrowing) Baseline and week 12 Mean Change From Baseline in Radiographic (X-ray) Progression of Joint Damage as Measured by Modified Sharp/Van Der Heijde Total Score Baseline and week 24 The Sharp-van der Heijde total score ranges from 0-528. Scores for erosion range from 0 to 5 in the hands and 0 to 10 in the feet and reflect erosion size, with 0 defined as no erosion and 3 defined as a large erosion passing the midline of the joint. If there is \> 1 erosion per joint, scores can be combined to give a maximum score of 5 per joint in the hands and 10 per joint in the feet (a maximum of 5 at each side of the joint). Joint space narrowing scores vary from 0 to 4 in both the hands and feet, with 0 being normal and 4 being the absence of joint space with evident ankylosis or subluxation. Gross osteolysis and pencil-in-cup change are scored separately and, if present, are assigned the maximum score for erosion and joint space narrowing for the same affected joint. Higher scores indicate increased joint damage.
Trial Locations
- Locations (15)
Clinical Pharmacology Study Group
🇺🇸Worcester, Massachusetts, United States
Arthritis Associates Of Mississippi
🇺🇸Jackson, Mississippi, United States
Box Arthritis And Rheumatology Of The Carolinas, Pllc
🇺🇸Charlotte, North Carolina, United States
Health Research Of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Physician Research Collaboration, Llc
🇺🇸Lincoln, Nebraska, United States
Altoona Center For Clinical Research
🇺🇸Duncansville, Pennsylvania, United States
Local Institution
🇨🇳Taoyuan, Taiwan
Seattle Rheumatology Associates
🇺🇸Seattle, Washington, United States
New England Research Associates, Llc
🇺🇸Trumbull, Connecticut, United States
San Diego Arthritis Medical Clinic
🇺🇸San Diego, California, United States
Sun Valley Arthritis Center, Ltd.
🇺🇸Peoria, Arizona, United States
Quincy Medical Group
🇺🇸Quincy, Illinois, United States
Centre De Recherche Musculo-Squelettique
🇨🇦Trois-rivieres, Quebec, Canada
Rockford Orthopedic Associates, Llc.
🇺🇸Rockford, Illinois, United States
East Penn Rheumatology Associates, P.C.
🇺🇸Bethlehem, Pennsylvania, United States