Abatacept With Methotrexate- Phase IIB

NCT00162266 | Completed Phase 2 Results

• 1 other identifier: IM101-100
• Study Type: interventional
• Target: 524
• Locations: 11 countries
• Sites: 57

Brief Summary

This study was conducted to assess the safety and tolerability of Abatacept combined with Methotrexate in participants with active rheumatoid arthritis (RA). The secondary objectives were to assess efficacy, pharmacodynamic marker activity, and immunogenicity of Abatacept combined with Methotrexate.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (14)

• Number of Responders to American College of Rheumatology 20% Improvement Criteria (ACR 20) at Day 180 of the Double-Blind (DB) Period

  ACR 20 response requires a participant to have a 20% reduction in the number of swollen and tender joints, and a reduction of 20% in three of the following five parameters: physician global assessment of disease, participant global assessment of disease, participant assessment of pain, C-reactive protein or erythrocyte sedimentation rate, and degree of disability in Health Assessment Questionnaire score. A participant achieved a sustained ACR 20 response if the participant had ACR 20 observed for at least 2 consecutive study visits.

  Day 180

• Participants Receiving Concomitant Disease Modifying Rheumatic Drugs and Biologics in Open-Label (OL) Period

  The number of participants receiving concomitant rheumatoid arthritis treatment with disease modifying rheumatic drugs and/or biologics.

  Day 360 to Day 3,060

• Number of Participants Experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) in OL Period

  AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with treatment.SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Related AE/SAE=Certain,Probable,Possible,or Missing relationship to drug.

  Day 360 to Day 3060

• Number of Participants With AEs of Special Interest in OL Period

  AEs were defined as any new untoward medical occurrence or worsening of a pre- existing medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest were those which may be associated with the use of immunomodulatory agents or infusion of therapeutic proteins. Acute infusional AEs were defined as those that occurred within 1 hour after the start of the infusion. Peri-Infusional AEs were defined as those that occurred within 24 hours after the start of the infusion.

  Day 360 to Day 3060

• Baseline Serum Immunoglobulin A (IgA) Over Time in OL Period

  Time-matched baseline (Day 0) values and post-baseline values were presented for each post-baseline visit and represent only that cohort of participants with measurements available at that post-baseline assessment. Mean Change from Baseline data for these cohorts are presented in Outcome Measure 6.

  Baseline (Day 0) and Days 360, 720,1080, 1440, and 1800

• Mean Change From Baseline (BL) in IgA Over Time in OL Period

  Blood samples for immunoglobulin assessments were obtained to determine change from baseline in serum IgA. Baseline data for these time-matched cohorts are presented in Outcome Measure 5.

  Baseline (Day 0) and Days 360, 720, 1080, 1440, and 1800

• Baseline Immunoglobulin G (IgG) Over Time in OL Period

  Time-matched baseline (Day 0) values and post-baseline vales were presented for each post-baseline visit and represent only that cohort of participants with measurements available at that post-baseline assessment. Mean Change from Baseline data for these cohorts are presented in Outcome Measure 8.

  Baseline (Day 0) and Days 360, 720, 1080, 1440 and 1800

• Mean Change From Baseline (BL) in IgG Over Time in OL Period

  Blood samples for immunoglobulin assessments were obtained to determine change from baseline in serum IgG. Baseline data for these cohorts are presented in Outcome Measure 7.

  Baseline (Day 0) and Days 360, 720, 1080, 1440, and 1800

• Baseline Immunoglobulin M (IgM) Over Time in OL Period

  Time-matched baseline (Day 0) values and post-baseline values were presented for each post-baseline visit and represent only that cohort of participants with measurements available at that post-baseline assessment. Mean Change from Baseline data for these cohorts are presented in Outcome Measure 10.

  Baseline (Day 0) and Days 360, 720,1080,1440, and 1800

• Mean Change From Baseline (BL) in IgM in OL Period

  Blood samples for immunoglobulin assessments were obtained to determine change from baseline in serum IgM. Baseline data for these time-matched cohorts are presented in Outcome Measure 9.

  Baseline (Day 0) and Days 360, 720, 1080, 1440, and 1800

• Number of Participants With Hematology Values Meeting Marked Abnormality Criteria in OL Period

  Day 360 to Day 3060

• Number of Participants With Liver and Kidney Function Values Meeting Marked Abnormality Criteria in OL Period

  Day 360 to Day 3060

• Number of Participants With Electrolyte Values Meeting Marked Abnormality Criteria in OL Period

  Day 360 to Day 3060

• Number of Participants With Glucose, Protein, Metabolites, and Urinalysis Values Meeting Marked Abnormality Criteria in OL Period

  Day 360 to Day 3060

Secondary Outcomes (54)

• Number of ACR 20 Responders in DB Period

  Days 15, 30, 60, 90, 120, 150,180, 240, 300, and 360

• Number of ACR 50 Responders in DB Period

  Day 15; Day 30; Day 60; Day 90; Day 120; Day 150; Day 180; Day 240; Day 300; Day 360

• Number of ACR 70 Responders in DB Period

  Day 15; Day 30; Day 60; Day 90; Day 120; Day 150; Day 180; Day 240; Day 300; Day 360

• ACR Numeric Values (ACR-N)

  Day 15; Day 30; Day 60; Day 90; Day 120; Day 150; Day 180; Day 240; Day 300; Day 360

• ACR-N Area Under The Curve (AUC) on Day 180 and Day 360

  Baseline and Day 180; Baseline and Day 360

Study Arms (4)

Abatacept (10 mg/Kg) - Open Label

EXPERIMENTAL

Drug: Abatacept (BMS-188667)

Abatacept (2 mg/kg) - Double blind

EXPERIMENTAL

Drug: Abatacept (BMS-188667)

Abatacept (10 mg/kg) - Double blind

EXPERIMENTAL

Drug: Abatacept (BMS-188667)

Placebo - Double blind

EXPERIMENTAL

Drug: Placebo

Interventions

Abatacept (BMS-188667) DRUG

IV, 10 mg/Kg, monthly, for the duration of the trial

Abatacept (10 mg/Kg) - Open Label

Placebo DRUG

Intravenous (IV) infusion, 0 mg/kg, infused intravenously for approximately 30 min, infusions on Days 1, 15, 30 and monthly thereafter for 12 months

Placebo - Double blind

Eligibility Criteria

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

You may qualify if:

• Double blind study phase:
• Males or females (not nursing and not pregnant), at least 18 years of age. Women of child bearing potential (WOCBP) are eligible if they are practicing effective contraceptive measures
• Subjects must meet the criteria of the American Rheumatism Association (1987) for the diagnosis of rheumatoid arthritis and the American College of Rheumatology (1991) functional classes I, II, or III
• Subjects have been taking Methotrexate (10-30 mg weekly) for at least 6 months, and at a stable dose for 28 days prior to treatment
• Washout/drug stabilization requirements (except Methotrexate) \[Informed consent must be signed before making any changes in RA therapy if those changes are solely for the purpose of this study\].
• Leflunomide or Infliximab have already been discontinued at least 60 days prior to enrollment (prior to signing of informed consent) and a total of 90 days prior to treatment. All other Disease Modifying Anti-Rheumatic Drugs (DMARDs) (except Methotrexate) have been withdrawn at least 28 days prior to treatment
• Oral corticosteroid treatment has been reduced to the equivalent of 10 mg or less prednisone daily and stabilized for at least 28 days prior to enrollment
• Eligibility of subjects for the study is based on their disease activity and anti-rheumatic treatment at the initial visit:
• Methotrexate monotherapy: Subject is receiving only Methotrexate, steroids, Non-steroidal anti-inflammatory drugs (NSAIDs) and will not require washout
• Combination therapy: Subject is receiving Methotrexate in combination with another DMARD(s) and will require washout
• At entry, Methotrexate monotherapy must have a disease activity:
• or more swollen joints (66 joint count)
• or more tender joints (68 joint count)
• C reactive protein (CRP) ≥.1 mg/dL (10 mg/L) at "Screening" visit
• At entry, combination therapy must have a disease activity (if subject does not satisfy the above):

You may not qualify if:

• Double blind study phase:
• Subjects who have at any time received treatment with BMS-188667 (Abatacept)
• Subjects who within 30 days of the Day 1 visit have received treatment with any investigational drug
• Subjects with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules)
• Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease. Concomitant medical conditions that in the opinion of the investigator might place the subject at unacceptable risk for participation in this study
• Mammogram requiring further investigation or biopsies leading to the diagnosis of a clinically significant abnormality. Complete evaluation of lesion is required before initiation of dosing
• Subjects with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection)
• Subjects who have a history of clinically significant drug or alcohol abuse, or admit to consumption of more than 1 alcoholic drink per day
• Subjects with evidence (as assessed by the investigator) of active or latent bacterial or viral infections at the time of potential enrollment, including subjects with evidence of Human Immunodeficiency Virus (HIV) infection, or hepatitis B or C infection
• Subjects with any serious or chronic infections such as pneumonia, pyelo-nephritis, renal infection, chest infection with bronchiectasis, or sinusitis in the previous 3 months
• Subjects with active tuberculosis requiring treatment within the previous 3 years
• Subjects with any opportunistic infections such as herpes zoster or cytomegalovirus (CMV) within the previous 2 months
• Subjects with severe asthma defined as \> 3 emergency room admissions in the last year or \> 3 treatments with oral steroids for asthma in the last year
• A history of either angioedema or anaphylaxis that was associated with a reaction to a drug
• Subjects with the following laboratory values:

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (57)

Local Institution

Birmingham, Alabama, United States

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Huntsville, Alabama, United States

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Long Beach, California, United States

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Highlands Ranch, Colorado, United States

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Largo, Florida, United States

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Titusville, Florida, United States

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West Palm Beach, Florida, United States

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Rome, Georgia, United States

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Chicago, Illinois, United States

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Wichita, Kansas, United States

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Cumberland, Maryland, United States

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Springfield, Massachusetts, United States

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Worcester, Massachusetts, United States

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Duluth, Minnesota, United States

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Lincoln, Nebraska, United States

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Albuquerque, New Mexico, United States

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Los Alamos, New Mexico, United States

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Albany, New York, United States

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Binghamton, New York, United States

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The Bronx, New York, United States

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Portland, Oregon, United States

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Duncansville, Pennsylvania, United States

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Sellersville, Pennsylvania, United States

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Amarillo, Texas, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Buenos Aries, Buenos Aries, Argentina

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Quilmes, Burenos Aires, Argentina

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Adelaide, South Australia, Australia

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Malvern, Victoria, Australia

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Perth, Western Australia, Australia

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Antwerp, Belgium

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Brussels, Belgium

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Ghent, Belgium

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Leuven, Belgium

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Mons, Belgium

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Edmonton, Alberta, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Ste-Foy, Quebec, Canada

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St. John's, Canada

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Montpellier, Cedex, France

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Strasbourg, Cedex, France

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Paris, France

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Berlin, Germany

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Freiburg im Breisgau, Germany

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Jena, Germany

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Cork, Cork, Ireland

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Nijmegen, Netherlands

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Muckleneuk, Gauteng, South Africa

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Cape Town, Western Cape, South Africa

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Cambridge, Cambridgeshire, United Kingdom

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Manchester, Greater Manchester, United Kingdom

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Maidstone, Kent, United Kingdom

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Leeds, Yorkshire, United Kingdom

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Related Publications (1)

• Westhovens R, Kremer JM, Emery P, Russell AS, Alten R, Barre E, Dougados M. Long-term safety and efficacy of abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: a 7-year extended study. Clin Exp Rheumatol. 2014 Jul-Aug;32(4):553-62. Epub 2014 Jul 8.

  PMID: 25005467 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Abatacept

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

clinical.trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: September 9, 2005
• First Posted: September 13, 2005
• Study Start: October 1, 2000
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: June 1, 2012
• Results First Posted: June 1, 2012

Record last verified: 2012-05

Locations

CA (7); GB (4); FR (3); US (26); AU (3); BE (5); ZA (2); NL (1); IE (1); AR (2); DE (3)