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

Rheumatoid Arthritis Clinical Trial

— RA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01404585
• Other study ID #: IM126-004
• Secondary ID: 2011-002024-40
• Status: Completed
• Phase: Phase 2
• First received: July 27, 2011
• Last updated: September 23, 2015
• Start date: September 2011
• Est. completion date: February 2013

Study information

• Verified date: September 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 a (TNF-a) 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Placebo
Tablets, Oral, 0 mg, twice daily, 12 weeks
• BMS-817399
Tablets, Oral, 200 mg, twice daily, 12 weeks
• BMS-817399
Tablets, Oral, 400mg, twice daily, 12 weeks

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Tucuman
Korea, Republic of	Local Institution	Daegu
Korea, Republic of	Local Institution	Gwangju
Korea, Republic of	Local Institution	Seoul
Korea, Republic of	Local Institution	Seoul
Mexico	Local Institution	D.f.	Distrito Federal
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Merida	Yucatan
Mexico	Local Institution	San Luis Potosi
Mexico	Local Institution	Tijuana	Baja California
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Yaroslavl
South Africa	Local Institution	Durban	Kwa Zulu Natal
South Africa	Local Institution	Panorama	Western Cape
South Africa	Local Institution	Pinelands	Western Cape
South Africa	Local Institution	Pretoria	Gauteng
Spain	Local Institution	Cordoba
Spain	Local Institution	Santiago De Compostela
Spain	Local Institution	Sevilla
United States	Altoona Center For Clinical Research	Duncansville	Pennsylvania
United States	Pharma Resource	East Providence	Rhode Island
United States	Paramount Medical Research & Consulting, Llc	Middleburg Heights	Ohio
United States	Desert Medical Advances	Palm Desert	California
United States	Sarasota Arthritis Research Center	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Korea, Republic of,  Mexico,  Russian Federation,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Activity Score using 28 joint count and C Reactive Protein (DAS28-CRP) change from baseline of BMS-817399 versus placebo		Baseline and at 12 weeks	No
Secondary	Safety assessments will be based on adverse event reports and the results of vital sign measurements, electrocardiogram, physical examinations, and clinical laboratory tests		16 weeks	Yes
Secondary	Proportion of subjects achieving 20% American College of Rheumatology (ACR) response in each treatment group		Day 15	No
Secondary	Proportion of subjects achieving 20% ACR response in each treatment group		Day 29	No
Secondary	Proportion of subjects achieving 20% ACR response in each treatment group		Day 57	No
Secondary	Proportion of subjects achieving 20% ACR response in each treatment group		Day 85	No
Secondary	Proportion of subjects achieving 50% ACR response in each treatment group		Day 15	No
Secondary	Proportion of subjects achieving 50% ACR response in each treatment group		Day 29	No
Secondary	Proportion of subjects achieving 50% ACR response in each treatment group		Day 57	No
Secondary	Proportion of subjects achieving 50% ACR response in each treatment group		Day 85	No
Secondary	Proportion of subjects achieving 70% ACR response in each treatment group		Day 15	No
Secondary	Proportion of subjects achieving 70% ACR response in each treatment group		Day 29	No
Secondary	Proportion of subjects achieving 70% ACR response in each treatment group		Day 57	No
Secondary	Proportion of subjects achieving 70% ACR response in each treatment group		Day 85	No
Secondary	Percent change from baseline in disability index of the Health Assessment Questionnaire (HAQ-DI)		Baseline and Day 15	No
Secondary	Percent change from baseline in disability index of the Health Assessment Questionnaire (HAQ-DI)		Baseline and Day 29	No
Secondary	Percent change from baseline in disability index of the Health Assessment Questionnaire (HAQ-DI)		Baseline and Day 57	No
Secondary	Percent change from baseline in disability index of the Health Assessment Questionnaire (HAQ-DI)		Baseline and Day 85	No
Secondary	To assess the minimum observed concentration (Cmin) of BMS-817399		Day 15, Day 29, Day 57 and Day 85	No

External Links

•   BMS clinical trial educational resource
•   BMS Clinical Trial Information
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form