Clinical trial NCT01404585: Proof-of-Concept Study With BMS-817399 to Treat Moderate to Severe Rheumatoid Arthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2011-07-28
Enrollment: 123
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 purpose of this study is to assess whether BMS-817399 in combination with Methotrexate is effective in treating moderate to severe rheumatoid arthritis.


Eligibility 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

Primary outcomes:
measure: Disease Activity Score using 28 joint count and C Reactive Protein (DAS28-CRP) change from baseline of BMS-817399 versus placebo
timeFrame: Baseline and at 12 weeks
Secondary outcomes:
measure: Safety assessments will be based on adverse event reports and the results of vital sign measurements, electrocardiogram, physical examinations, and clinical laboratory tests
timeFrame: 16 weeks
measure: Proportion of subjects achieving 20% American College of Rheumatology (ACR) response in each treatment group
timeFrame: Day 15
measure: Proportion of subjects achieving 20% ACR response in each treatment group
timeFrame: Day 29
measure: Proportion of subjects achieving 20% ACR response in each treatment group
timeFrame: Day 57
measure: Proportion of subjects achieving 20% ACR response in each treatment group
timeFrame: Day 85
measure: Proportion of subjects achieving 50% ACR response in each treatment group
timeFrame: Day 15
measure: Proportion of subjects achieving 50% ACR response in each treatment group
timeFrame: Day 29
measure: Proportion of subjects achieving 50% ACR response in each treatment group
timeFrame: Day 57
measure: Proportion of subjects achieving 50% ACR response in each treatment group
timeFrame: Day 85
measure: Proportion of subjects achieving 70% ACR response in each treatment group
timeFrame: Day 15
measure: Proportion of subjects achieving 70% ACR response in each treatment group
timeFrame: Day 29
measure: Proportion of subjects achieving 70% ACR response in each treatment group
timeFrame: Day 57
measure: Proportion of subjects achieving 70% ACR response in each treatment group
timeFrame: Day 85
measure: Percent change from baseline in disability index of the Health Assessment Questionnaire (HAQ-DI)
timeFrame: Baseline and Day 15
measure: Percent change from baseline in disability index of the Health Assessment Questionnaire (HAQ-DI)
timeFrame: Baseline and Day 29
measure: Percent change from baseline in disability index of the Health Assessment Questionnaire (HAQ-DI)
timeFrame: Baseline and Day 57
measure: Percent change from baseline in disability index of the Health Assessment Questionnaire (HAQ-DI)
timeFrame: Baseline and Day 85
measure: To assess the minimum observed concentration (Cmin) of BMS-817399
timeFrame: Day 15, Day 29, Day 57 and Day 85
Other outcomes:
Locations:
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: Sarasota
country: United States
facility: Sarasota Arthritis Research Center
state: Florida
city: Middleburg Heights
country: United States
facility: Paramount Medical Research & Consulting, Llc
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center For Clinical Research
state: Pennsylvania
city: East Providence
country: United States
facility: Pharma Resource
state: Rhode Island
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Tucuman
country: Argentina
facility: Local Institution
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Gwangju
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Tijuana
country: Mexico
facility: Local Institution
state: Baja California
city: D.f.
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Merida
country: Mexico
facility: Local Institution
state: Yucatan
city: San Luis Potosi
country: Mexico
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Yaroslavl
country: Russian Federation
facility: Local Institution
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Durban
country: South Africa
facility: Local Institution
state: Kwa Zulu Natal
city: Panorama
country: South Africa
facility: Local Institution
state: Western Cape
city: Pinelands
country: South Africa
facility: Local Institution
state: Western Cape
city: Cordoba
country: Spain
facility: Local Institution
city: Santiago De Compostela
country: Spain
facility: Local Institution
city: Sevilla
country: Spain
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: