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

NCT01404585 | Completed Phase 2 DMC

• 2 other identifiers: IM126-0042011-002024-40
• Study Type: interventional
• Target: 123
• Locations: 7 countries
• Sites: 29

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (18)

• 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

• Proportion of subjects achieving 20% American College of Rheumatology (ACR) response in each treatment group

  Day 15

• Proportion of subjects achieving 20% ACR response in each treatment group

  Day 29

• Proportion of subjects achieving 20% ACR response in each treatment group

  Day 57

• Proportion of subjects achieving 20% ACR response in each treatment group

  Day 85

Study Arms (3)

Arm 1: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Arm 2: BMS-817399 (200 mg)

EXPERIMENTAL

Drug: BMS-817399

Arm 3: BMS-817399 (400 mg)

EXPERIMENTAL

Drug: BMS-817399

Interventions

Placebo DRUG

Tablets, Oral, 0 mg, twice daily, 12 weeks

Arm 1: Placebo

BMS-817399 DRUG

Tablets, Oral, 200 mg, twice daily, 12 weeks

Arm 2: BMS-817399 (200 mg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:
• Oral or injectable azathioprine, gold, D-Penicillamine, cyclosporine, anakinra, etanercept, parenteral or intra-articular corticosteroids: 30 days
• Leflunomide: 6 months unless an active washout with Cholestyramine has been performed
• Mycophenolate mofetil, cyclophosphamide, tacrolimus or other immunosuppressant: 3 months

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (29)

Desert Medical Advances

Palm Desert, California, 92260, United States

Location

Sarasota Arthritis Research Center

Sarasota, Florida, 34239, United States

Location

Paramount Medical Research & Consulting, Llc

Middleburg Heights, Ohio, 44130, United States

Location

Altoona Center For Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Pharma Resource

East Providence, Rhode Island, 02915, United States

Location

Local Institution

Buenos Aires, Buenos Aires, 1015, Argentina

Location

Local Institution

Buenos Aires, Buenos Aires, 1426, Argentina

Location

Local Institution

Capital Federal, Buenos Aires, 1425, Argentina

Location

Local Institution

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Local Institution

Tijuana, Estado de Baja California, 22010, Mexico

Location

Local Institution

Guadalajara, Jalisco, 44158, Mexico

Location

Local Institution

Guadalajara, Jalisco, 44690, Mexico

Location

Local Institution

Guadalajara, Jalisco, 45050, Mexico

Location

Local Institution

D.f., Mexico City, 06700, Mexico

Location

Local Institution

San Luis Potosí City, San Luis Potosí, 78200, Mexico

Location

Local Institution

Mérida, Yucatán, 97000, Mexico

Location

Local Institution

Moscow, 115522, Russia

Location

Local Institution

Yaroslavl, 150003, Russia

Location

Local Institution

Pretoria, Gauteng, 0181, South Africa

Location

Local Institution

Durban, KwaZulu-Natal, 4001, South Africa

Location

Local Institution

Panorama, Western Cape, 7500, South Africa

Location

Local Institution

Pinelands, Western Cape, 7405, South Africa

Location

Local Institution

Daegu, 705-718, South Korea

Location

Local Institution

Gwangju, 501-757, South Korea

Location

Local Institution

Seoul, 110-744, South Korea

Location

Local Institution

Seoul, 143-729, South Korea

Location

Local Institution

Córdoba, 14004, Spain

Location

Local Institution

Santiago de Compostela, 15706, Spain

Location

Local Institution

Seville, 41071, Spain

Location

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

1-(1-(4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)-3-(2-hydroxy-2-methylpropyl)urea

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2011
• First Posted: July 28, 2011
• Study Start: September 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: October 12, 2015

Record last verified: 2015-09

Locations

US (5); ME (7); ZA (4); RU (2); ES (3); KR (4); AR (4)