Phase IIB Rheumatoid Arthritis Dose Ranging Study for BMS-945429 in Subjects Who Are Not Responding to Methotrexate

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01373151
First received: June 13, 2011
Last updated: September 22, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: BMS-945429 Placebo
Biological: BMS-945429
Drug: Methotrexate
Drug: Methotrexate Placebo
Drug: Adalimumab Placebo
Drug: Adalimumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase IIB , Randomized, Multi-Center, Double-Blind, Dose-Ranging, Placebo/Active Controlled Study to Evaluate the Efficacy and Safety of BMS-945429 Subcutaneous Injection With or Without Methotrexate in Subjects With Moderate to Severe Rheumatoid Arthritis With Inadequate Response to Methotrexate.

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Proportion of subjects achieving an American College of Rheumatology (ACR) 20 response rate [ Time Frame: At 12 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects with ACR 20 response [ Time Frame: At weeks 24 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving ACR 50 response rate [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Proportion of subjects achieving ACR 70 response rate [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Mean change from baseline in disease activity as measured by Disease Activity Score 28 C-reactive protein (DAS28-CRP) [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Proportion of subjects with remission by DAS28-CRP [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Mean change from baseline in Clinical Disease Activity Index (CDAI) [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Proportion of subjects with remission by CDAI [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Mean change from baseline in Simplified Disease Activity Index (SDAI) [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Proportion of subjects with remission by SDAI [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Proportion of subjects with remission rate by Boolean definition [ Time Frame: At weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Mean change from baseline in Health Assessment Questionnaire (HAQ) disability Index [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Mean change from baseline in Short Form 36 (SF-36) as measured by physical and mental components as well as 8 individual domain scores [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Mean change from baseline in fatigue severity (VAS) [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Mean change from baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) as measured by 4 domain scores [ Time Frame: Baseline (Day 1), To weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Mean change from baseline in radiographic progression of synovitis, osteitis (bone marrow edema), bone erosion and cartilage loss (joint-space narrowing) (MRI) [ Time Frame: Baseline (Day 1) and To weeks 12 ] [ Designated as safety issue: No ]
  • Mean change from baseline in radiographic progression of joint damage as measured by modified Sharp/van der Heijide scores (X-ray) [ Time Frame: Baseline (Day 1) and To weeks 24 ] [ Designated as safety issue: No ]
  • Safety will be measured by adverse events, clinically significant changes in vital signs, physical exams and ECG, laboratory test abnormality and immunogenicity changes from baseline [ Time Frame: Upto double-blind period (48 weeks) ] [ Designated as safety issue: Yes ]

Enrollment: 418
Study Start Date: June 2011
Estimated Study Completion Date: August 2020
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm 1
BMS-945429 Placebo/BMS-945429+Methotrexate+Adalimumab Placebo
Drug: BMS-945429 Placebo
Injection, Subcutaneous, 0 mg, Every 4 weeks, Day 1 - Week 24 only
Biological: BMS-945429
Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48
Drug: Methotrexate
Tablets, Oral, 15 mg, Weekly, Day 1 - Week 24 only
Drug: Adalimumab Placebo
Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks
Experimental: Arm 2
BMS-945429 + Methotrexate + Adalimumab Placebo
Biological: BMS-945429
Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks
Drug: Methotrexate
Tablets, Oral, 15 mg, Weekly, 48 weeks
Drug: Adalimumab Placebo
Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks
Experimental: Arm 3
BMS-945429 + Methotrexate + Adalimumab Placebo
Biological: BMS-945429
Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks
Drug: Methotrexate
Tablets, Oral, 15 mg, Weekly, 48 weeks
Drug: Adalimumab Placebo
Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks
Experimental: Arm 4
BMS-945429 + Methotrexate + Adalimumab Placebo
Biological: BMS-945429
Injection, Subcutaneous, 25 mg, Every 4 weeks, Day 1 - Week 24 only
Biological: BMS-945429
Injection, Subcutaneous, 200 mg, Every 4 weeks, Week 25 - Week 48
Drug: Methotrexate
Tablets, Oral, 15 mg, Weekly, 48 weeks
Drug: Adalimumab Placebo
Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks
Experimental: Arm 5
BMS-945429 + Methotrexate/Methotrexate Placebo + Adalimumab Placebo
Biological: BMS-945429
Injection, Subcutaneous, 200 mg, Every 4 weeks, 48 weeks
Drug: Methotrexate Placebo
Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only
Drug: Methotrexate
Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only
Drug: Adalimumab Placebo
Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks
Experimental: Arm 6
BMS-945429 + Methotrexate/Methotrexate Placebo+Adalimumab Placebo
Biological: BMS-945429
Injection, Subcutaneous, 100 mg, Every 4 weeks, 48 weeks
Drug: Methotrexate Placebo
Tablets, Oral, 0 mg, Weekly, Day 1 - Week 24 only
Drug: Methotrexate
Tablets, Oral, 15 mg, Weekly, Week 25 - Week 48 only
Drug: Adalimumab Placebo
Injection, Subcutaneous, 0 mg, Every 2 weeks, 48 weeks
Active Comparator: Arm 7
Adalimumab + Methotrexate
Drug: Methotrexate
Tablets, Oral, 15 mg, Weekly, 48 weeks
Drug: Adalimumab
Injection, Subcutaneous, 40 mg, Every 2 weeks, 48 weeks

  Eligibility

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

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Previously received or currently receiving concomitant biologic therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01373151

  Show 100 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: NCT01373151     History of Changes
Other Study ID Numbers: IM133-001, 2010-023956-99
Study First Received: June 13, 2011
Last Updated: September 22, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
Korea: Food and Drug Administration
Taiwan: Department of Health
Taiwan: National Bureau of Controlled Drugs
Canada: Health Canada
Hungary: National Institute of Pharmacy
Russia: Ethics Committee
Russia: FSI Scientific Center of Expertise of Medical Application
Germany: Federal Institute for Drugs and Medical Devices
Germany: Federal Office for Radiation Protection
Germany: Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Japan: Ministry of Health, Labor and Welfare
Japan: Pharmaceuticals and Medical Devices Agency
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: Ethics Committee
Brazil: National Health Surveillance Agency
Chile: Instituto de Salud Pública de Chile
Peru: Instituto Nacional de Salud
Mexico: Federal Commission for Sanitary Risks Protection
Belgium: The Federal Public Service (FPS) Health, Food Chain Safety and Environment
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Italy: Ministry of Health
Italy: National Bioethics Committee
Italy: National Institute of Health
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Methotrexate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014