A Phase III Study of BMS-188667 in Patients With Active Rheumatoid Arthritis and Inadequate Response to Methotrexate - Full Text View

Sponsor:	Bristol-Myers Squibb
Information provided by:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00048568

Purpose

Short Term: The purpose of this clinical research study is to learn if BMS-188667 in combination with methotrexate is better than methotrexate alone in subjects that have active rheumatoid arthritis and are not responding to methotrexate. The safety of this treatment will also be studied.

Long Term Extension: The purpose of this amendment is to provide subjects who have completed the initial 12-month double-blind treatment period the opportunity to receive open label treatment with active drug treatment until BMS-188667 is approved in the local country or until clinical development has been discontinued.

Condition	Intervention	Phase
Rheumatoid Arthritis	Drug: BMS-188667 Drug: Methotrexate Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment

Resource links provided by NLM:

MedlinePlus related topics: Rheumatoid Arthritis

Drug Information available for: Methotrexate Abatacept

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Compare the clinical efficacy of BMS-188667 used in combination with methotrexate versus methotrexate alone on: Symptomatic relief as measured by ACR20 following 6 months of treatment [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
Compare the clinical efficacy of BMS-188667 used in combination with methotrexate versus methotrexate alone on: Physical function as measured by the disability index of the HAQ at 12 months [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
Compare the clinical efficacy of BMS-188667 used in combination with methotrexate versus methotrexate alone on: Structural damage as assessed by erosion scores using a Genant-modified method at 12 months of treatment [ Time Frame: Day 365 ] [ Designated as safety issue: Yes ]
The primary objective of long term extension is to assess the safety and long term tolerability of BMS-188667 in subjects who have completed the initial 12-month double-blind treatment period [ Time Frame: Long term extension ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Determine the effect of BMS-188667 in combination with methotrexate on structural damage as assessed by total and joint space narrowing score using a Genant-modified Sharp method at 12 months of treatment [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
Compare ACR 50 and ACR 70 [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
Assessed ACR 20, ACR 50, and ACR 70 [ Time Frame: Over time ] [ Designated as safety issue: No ]
Determine the proportion of subjects receiving BMS-188667 in combination with methotrexate who achieve a major clinical response (continuous ACR 70) [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
Assess disease activity as measured by Disease Activity Score-28 (DAS-28) [ Time Frame: Day 1, Day 169, and Day 365 ] [ Designated as safety issue: No ]
Assess the safety of chronic use of BMS-188667 in combination with methotrexate [ Time Frame: every 28 months ] [ Designated as safety issue: No ]
Assess the discontinuation rate in subjects receiving BMS-188667 in combination with methotrexate [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
Assess the incidence of new tender and swollen joints and 100% reduction in joint counts [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
Assess the immunogenicity of BMS-188667 in combination with methotrexate [ Time Frame: Day 1, Day 169, and Day 365 ] [ Designated as safety issue: No ]
Assess changes of surrogate markers (RF, CRP, ESR, IL2-r) in subjects receiving BMS-188667 in combination with methotrexate [ Time Frame: Day 169 ] [ Designated as safety issue: Yes ]
Assess the changes of functional status as measured by the disability index and individual components of the HAQ in subjects receiving BMS-188667 in combination with methotrexate [ Time Frame: Day 169 ] [ Designated as safety issue: No ]
Assess the change of subject's health-related quality of life, as measured by the SF-36 questionnaire in subjects receiving BMS-188667 in combination with methotrexate [ Time Frame: Day 1, Day 29, Day 85, Day 169 ] [ Designated as safety issue: No ]
Assess the pharmacokinetics of BMS-188667 [ Time Frame: Day 1-Day 169, Day 225, Day 281, Day 337 ] [ Designated as safety issue: Yes ]
Determine the effect of BMS-188667 in combination with methotrexate on structural damage as assessed by x-ray evaluation in subjects with RA after two years of treatment [ Time Frame: Day 729 ] [ Designated as safety issue: Yes ]
Assess chx of functional status measured by disability index & individual components of HAQ in subjects receiving BMS-188667 in combination with methotrexate to determine if any improvement in HAQ associated with BMS-188667 treatment - long-term adm [ Time Frame: Day 365 and over time ] [ Designated as safety issue: No ]
Assess ACR 20, ACR 50, and ACR 70 [ Time Frame: over time ] [ Designated as safety issue: No ]
Determine the proportion of subjects receiving BMS-188667 in combination with methotrexate who achieve a major clinical response (continuous ACR 70 for six months) [ Time Frame: Day 365 ] [ Designated as safety issue: No ]
Assess disease activity as measured by Disease Activity Score-28 (DAS-28), at each quarterly visit [ Time Frame: every 3 months ] [ Designated as safety issue: Yes ]
Assess the immunogenicity of BMS-188667 in combination with methotrexate [ Time Frame: every 6 months ] [ Designated as safety issue: Yes ]
Assess changes of surrogate markers (RF, CRP, ESR, IL-6, MMP-3) in subjects receiving BMS-188667 in combination with methotrexate [ Time Frame: CRP & ESR-every 3 months; all other tests - every 6 months ] [ Designated as safety issue: Yes ]
Assess the change of subject's health-related quality of life, as measured by the SF-36 questionnaire in subjects receiving BMS-188667 in combination with methotrexate [ Time Frame: every 6 months ] [ Designated as safety issue: No ]

Enrollment:	656
Study Start Date:	December 2002
Estimated Study Completion Date:	October 2009
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A1: Experimental Short Term	Drug: BMS-188667 IV Solution, Intravenous, - Weight Titered (500 mg < 60 kg); (750 mg 60-100 kg), )1 gram > 100 kg), Day 1, Day 15, Day 29; every 28 days thereafter, 1 year Drug: Methotrexate Tablets, Oral, >= 15 mg, weekly, 1 year
A2: Placebo Comparator Short Term	Drug: Methotrexate Tablets, Oral, >= 15 mg, weekly, 1 year Drug: Placebo IV solution, Intravenous, D5W, Day 1, Day 15, Day 29; every 28 days thereafter, 1 year
BMS-188667 Open Label Long Term Extension	Drug: BMS-188667 IV Solution, Intravenous, - Weight Titered (500 mg < 60 kg); (750 mg 60-100 kg), )1 gram > 100 kg), every 28 days Drug: Methotrexate Tablets, Oral, ≥ 15 mg, weekly

Eligibility

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

Criteria

Rheumatoid Arthritis for greater than 1 year from the time of initial diagnosis of RA.
Patients must have been taking methotrexate for at least 3 months with at least a weekly dose of 15 mg.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00048568

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Locations

United States, Alabama
Local Institution
Mobile, Alabama, United States
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Birmingham, Alabama, United States
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Huntsville, Alabama, United States
United States, Arizona
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Scottsdale, Arizona, United States
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Phoenix, Arizona, United States
United States, California
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Long Beach, California, United States
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Rancho Mirage, California, United States
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La Jolla, California, United States
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Corona, California, United States
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Irvine, California, United States
United States, Colorado
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Colorado Springs, Colorado, United States
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Denver, Colorado, United States
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Aurora, Colorado, United States
United States, Connecticut
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Hamden, Connecticut, United States
United States, District of Columbia
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Washington, District of Columbia, United States
United States, Florida
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Sarasota, Florida, United States
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Gainsville, Florida, United States
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Palm Harbor, Florida, United States
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Fort Lauderdale, Florida, United States
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St. Petersburg, Florida, United States
United States, Illinois
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Rockford, Illinois, United States
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Chicago, Illinois, United States
United States, Kansas
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Wichita, Kansas, United States
United States, Maryland
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Cumberland, Maryland, United States
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Coeur d'Alene, Maryland, United States
United States, Massachusetts
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Springfield, Massachusetts, United States
United States, Minnesota
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Duluth, Minnesota, United States
United States, Nebraska
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Lincoln, Nebraska, United States
United States, New Jersey
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New Brunswick, New Jersey, United States
United States, New Mexico
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Albuquerque, New Mexico, United States
United States, New York
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Syracuse, New York, United States
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Bronx, New York, United States
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Binghamton, New York, United States
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Albany, New York, United States
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New York, New York, United States
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Mineola, New York, United States
United States, North Carolina
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Wilmington, North Carolina, United States
United States, Ohio
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Cincinnati, Ohio, United States
United States, Oklahoma
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Oklahoma City, Oklahoma, United States
United States, Pennsylvania
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Duncansville, Pennsylvania, United States
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Sellersville, Pennsylvania, United States
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Norristown, Pennsylvania, United States
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Willow Grove, Pennsylvania, United States
United States, South Carolina
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North Charleston, South Carolina, United States
United States, Texas
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San Antonio, Texas, United States
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Austin, Texas, United States
United States, Virginia
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Arlington, Virginia, United States
United States, Wisconsin
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Milwaukee, Wisconsin, United States

Sponsors and Collaborators

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trials Disclosure This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

Publications:

Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechinski J, Li T, Ge Z, Becker JC, Westhovens R. Effects of abatacept in patients with methotrexate-resistant active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2006 Jun 20;144(12):865-76. Summary for patients in: Ann Intern Med. 2006 Jun 20;144(12):I18.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Kremer JM, Genant HK, Moreland LW, Russell AS, Emery P, Abud-Mendoza C, Szechiński J, Li T, Teng J, Becker JC, Westhovens R. Results of a two-year followup study of patients with rheumatoid arthritis who received a combination of abatacept and methotrexate. Arthritis Rheum. 2008 Apr;58(4):953-63.

Responsible Party:	Bristol-Myers Squibb ( Study Director )
Study ID Numbers:	IM101-102
Study First Received:	November 2, 2002
Last Updated:	September 23, 2009
ClinicalTrials.gov Identifier:	NCT00048568 History of Changes
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Arthritis, Rheumatoid
Reproductive Control Agents
Abatacept
Musculoskeletal Diseases
Arthritis
Therapeutic Uses
Abortifacient Agents
Connective Tissue Diseases

Methotrexate
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Autoimmune Diseases
Immune System Diseases
Joint Diseases
Enzyme Inhibitors
Rheumatic Diseases
Abortifacient Agents, Nonsteroidal
Folic Acid Antagonists
Immunosuppressive Agents
Pharmacologic Actions
Antirheumatic Agents

ClinicalTrials.gov processed this record on November 27, 2009