Resumen

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.

Descripción detallada

All participants who completed the 12-month double-blind study period were eligible to continue in the open-label study. Participants received placebo, Abatacept 2 mg/kg, or Abatacept 10 mg/kg in the double-blind study. Participants receiving placebo in the double-blind study were switched 1:1 to continued treatment with placebo or Abatacept 2 mg/kg. Participants receiving Abatacept 2 mg/kg or Abatacept 10 mg/kg continued at the double-blind study dosage. After results from the double-blind period became available, all participants were switched to a weight-tiered 10 mg/kg dose of Abatacept. Open label study design: Single group assignment, Single arm, Open label,

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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):
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 All other Disease Modifying Anti-Rheumatic Drugs (DMARDs) (except Methotrexate) have been withdrawn at least 28 days prior to treatment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)
No restriction on C-reactive protein (CRP)
In addition
All subjects who were on combination therapy at entry must undergo a 28 day washout period of DMARDs other than Methotrexate. After the washout/drug stabilization and prior to randomization such subjects must have:
or more swollen joints (66 joint count)
or more tender joints (68 joint count)
C reactive protein (CRP) ≥ 1 mg/dL (10 mg/L)
Subject is willing to participate in the study and willing to sign the informed consent
Open label study phase:
Participants that have completed the initial short term portion (double blind) of the study

Criterios de exclusión

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:
Hemoglobin \< 8.5 g/dL
White blood cells \< 3000/mm3
Platelets \< 100,000/mm3
Serum creatinine \> 2 times upper limit of normal
Serum Alanine aminotransferase (ALAT) or Aspartate aminotransferase (ASAT) \> 2 times upper limit of normal
Any other lab values that in the opinion of the investigator might place the subject at unacceptable risk for participation in this study
Open label study phase:

Intervenciones

drug

Abatacept (BMS-188667)

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

drug

Abatacept (BMS-188667)

Intravenous (IV) infusion, 2 mg/kg, infused intravenously for approximately 30 min, infusions on Days 1, 15, 30 and monthly thereafter for 12 months

drug

Abatacept (BMS-188667)

Intravenous (IV) infusion, 10 mg/kg, infused intravenously for approximately 30 min, infusions on Days 1, 15, 30 and monthly thereafter for 12 months

drug

Placebo

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

A Phase IIB, Multi-Center, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Clinical Efficacy of Two Different Doses of BMS-188667 Administered Intravenously to Subjects With Active Rheumatoid Arthritis While Receiving Methotrexate

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Abatacept (BMS-188667)

Abatacept (BMS-188667)

Abatacept (BMS-188667)

Placebo

Ubicaciones

Local Institution

Local Institution

Patrocinadores