Proof-of-Concept Study With BMS-817399 to Treat Moderate to Severe Rheumatoid Arthritis (RA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01404585
First received: July 27, 2011
Last updated: June 17, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to assess whether BMS-817399 in combination with Methotrexate is effective in treating moderate to severe rheumatoid arthritis.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Placebo
Drug: BMS-817399
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of BMS-817399 in Adults With Active, Moderate to Severe Rheumatoid Arthritis and Inadequate Response to Methotrexate

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Disease Activity Score using 28 joint count and C Reactive Protein (DAS28-CRP) change from baseline of BMS-817399 versus placebo [ Time Frame: Baseline and at 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety assessments will be based on adverse event reports and the results of vital sign measurements, electrocardiogram, physical examinations, and clinical laboratory tests [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
  • Proportion of subjects achieving 20% American College of Rheumatology (ACR) response in each treatment group [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving 20% ACR response in each treatment group [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving 20% ACR response in each treatment group [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving 20% ACR response in each treatment group [ Time Frame: Day 85 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving 50% ACR response in each treatment group [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving 50% ACR response in each treatment group [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving 50% ACR response in each treatment group [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving 50% ACR response in each treatment group [ Time Frame: Day 85 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving 70% ACR response in each treatment group [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving 70% ACR response in each treatment group [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving 70% ACR response in each treatment group [ Time Frame: Day 57 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving 70% ACR response in each treatment group [ Time Frame: Day 85 ] [ Designated as safety issue: No ]
  • Percent change from baseline in disability index of the Health Assessment Questionnaire (HAQ-DI) [ Time Frame: Baseline and Day 15 ] [ Designated as safety issue: No ]
  • Percent change from baseline in disability index of the Health Assessment Questionnaire (HAQ-DI) [ Time Frame: Baseline and Day 29 ] [ Designated as safety issue: No ]
  • Percent change from baseline in disability index of the Health Assessment Questionnaire (HAQ-DI) [ Time Frame: Baseline and Day 57 ] [ Designated as safety issue: No ]
  • Percent change from baseline in disability index of the Health Assessment Questionnaire (HAQ-DI) [ Time Frame: Baseline and Day 85 ] [ Designated as safety issue: No ]
  • To assess the minimum observed concentration (Cmin) of BMS-817399 [ Time Frame: Day 15, Day 29, Day 57 and Day 85 ] [ Designated as safety issue: No ]

Enrollment: 123
Study Start Date: September 2011
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm 1: Placebo Drug: Placebo
Tablets, Oral, 0 mg, twice daily, 12 weeks
Experimental: Arm 2: BMS-817399 (200 mg) Drug: BMS-817399
Tablets, Oral, 200 mg, twice daily, 12 weeks
Experimental: Arm 3: BMS-817399 (400 mg) Drug: BMS-817399
Tablets, Oral, 400mg, twice daily, 12 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects, 18 years of age or older, with rheumatoid arthritis (RA) for at least 6 months prior to screening
  • Subjects must have a tender joint count of at least 6 (28 joint count), swollen joint count of at least 6 (28 joint count) at screening. All subjects must have clinical evidence of synovitis in one hand/wrist at screening
  • Serum C-reactive protein (hsCRP) above upper limits of normal at screening
  • Subjects must have been treated with and tolerated Methotrexate (MTX) therapy at a weekly oral or parenteral dose ≥ 10 mg for ≥ 4 months prior to screening. Dose must be stable, with no change in route of administration, for ≥ 6 weeks prior to randomization. A MTX weekly dose as low as 7.5 mg is permitted if intolerance to doses ≥10 mg has been documented in the subject's medical history
  • Subjects must be receiving folic acid, folinic acid, or leucovorin supplementation at a stable dose for at least 4 weeks prior to randomization
  • Subjects who were previously treated with up to two tumor necrosis factor α (TNF-α) inhibitors
  • If taking antimalarials (e.g. hydroxychloroquine or chloroquine), subject must have been on a stable dose for ≥ 4 months prior to randomization
  • If taking non-steroidal anti-inflammatory drugs (NSAIDs), subjects must have been on stable doses for ≥ 2 weeks prior to randomization
  • If taking oral corticosteroids, daily doses must be ≤ 10 mg/day of prednisone or equivalent and stable for ≥ 4 weeks before randomization
  • Subject is willing to participate to the study and has signed the informed consent prior to undergoing any screening procedures
  • Women of childbearing potential (WOCBP) and men must agree to use at least two acceptable methods to avoid pregnancy for the entire study period and until 60 days (for women) and 90 days (for men) after the last dose of BMS-817399. WOCBP must have a negative urine pregnancy test at screening, randomization and at scheduled visits throughout the study

Exclusion Criteria:

  • Arthritis onset prior to 16 years of age or subjects with documented juvenile RA
  • Subjects who are bed- or wheelchair-bound
  • Subjects with other autoimmune diseases or arthritis syndromes
  • Women who are pregnant, breastfeeding or with a positive pregnancy test at screening or prior to randomization
  • Subjects who have any condition that could impact upon the absorption of study drug (i.e., gastric stapling, duodenal surgery, malabsorption syndrome)
  • Subjects with a history of, or a concurrent severe, progressive, or uncontrolled disease (other than RA) that in the opinion of the investigator might place the subject at unacceptable risk for participation in this study
  • Subjects who have present or previous (last 5 years) malignancies, except history of cured squamous or basal skin cell carcinoma or cured breast or cervical cancer
  • Subjects at risk for tuberculosis (TB) or with evidence of TB clinical history, chest X rays or tuberculin skin test
  • Subjects with evidence of active or latent bacterial or viral infections (including human immunodeficiency virus); Positive blood screen for hepatitis B surface antigen or hepatitis C antibody
  • Subjects with any serious bacterial infection within the last 2 months, unless treated and resolved with antibiotics
  • Subjects who have clinically significant drug or alcohol abuse or known cirrhosis including alcoholic cirrhosis
  • If a subject has received any of the following treatments, the indicated washout period prior to randomization must be followed:

    1. Oral or injectable azathioprine, gold, D-Penicillamine, cyclosporine, anakinra, etanercept, parenteral or intra-articular corticosteroids: 30 days
    2. Leflunomide: 6 months unless an active washout with Cholestyramine has been performed
    3. Mycophenolate mofetil, cyclophosphamide, tacrolimus or other immunosuppressant: 3 months
    4. Adalimumab, Infliximab, Golimumab, Certolizumab pegol, Abatacept or Tocilizumab: 60 days
    5. Rituximab or any B-cell depleting agent: 1 year
  • Use CYP3A4 inhibitors or inducers during the study
  • Subjects with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5x upper limit of normal (ULN), total bilirubin ≥ 1.4x ULN, estimated glomerular filtration rate (GFR) < 50 mL/min/1.73m2, hemoglobin < 10.0 g/dL, white blood cell count < 3,500/mm3, absolute neutrophil count < 1,700/mm3 or platelets < 125,000/mm3
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01404585

  Show 29 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01404585     History of Changes
Other Study ID Numbers: IM126-004, 2011-002024-40
Study First Received: July 27, 2011
Last Updated: June 17, 2013
Health Authority: United States: Food and Drug Administration

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 July 23, 2014