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

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:

Genetics Home Reference related topics: rheumatoid arthritis

MedlinePlus related topics: Arthritis Rheumatoid Arthritis

Drug Information available for: Methotrexate Methotrexate sodium Adalimumab

U.S. FDA Resources

Further study details as provided by Alder Biopharmaceuticals, Inc.:

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
Study Completion Date:	June 2015
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 (Adult, Senior)
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

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Sponsors and Collaborators

Alder Biopharmaceuticals, Inc.

Investigators


Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information This link exits the ClinicalTrials.gov site

BMS clinical trial educational resource This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

FDA Safety Alerts and Recalls This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Weinblatt ME, Mease P, Mysler E, Takeuchi T, Drescher E, Berman A, Xing J, Zilberstein M, Banerjee S, Emery P. The efficacy and safety of subcutaneous clazakizumab in patients with moderate-to-severe rheumatoid arthritis and an inadequate response to methotrexate: results from a multinational, phase IIb, randomized, double-blind, placebo/active-controlled, dose-ranging study. Arthritis Rheumatol. 2015 Oct;67(10):2591-600. doi: 10.1002/art.39249.


Responsible Party:	Alder Biopharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT01373151 History of Changes
Other Study ID Numbers:	IM133-001 2010-023956-99
Study First Received:	June 13, 2011
Last Updated:	July 24, 2015
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 Methotrexate Adalimumab 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 Antirheumatic Agents Nucleic Acid Synthesis Inhibitors Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on September 23, 2016