A Phase IIIB multicentre, randomized, double*blind, double dummy study to compare the efficacy and safety of abatacept administered subcutaneously and intravenously in subjects with rheumatoid arthritis, receiving background methotrexate, and experiencing an inadequate response to methotrexate.
- Conditions
- Rheumatoid Arthritis10003816
- Registration Number
- NL-OMON31814
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 3
1) Signed Written Informed Consent
2) 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. (protocol appendices 3 and 4).
c) Subjects with stable renal, endocrine, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological or cerebral disease(s) (eg, diabetes mellitus, congestive heart failure, chronic obstructive pulmonary disease) will be allowed to participate in this study.
d) Subjects who are considered methotrexate inadequate responders by a treating physician or investigator. Subjects must have been taking methotrexate for at least 3 months at a minimal weekly dose of 15 mg, and at a stable dose for 28 days prior to randomization.
a) Men and women, ages >= 18
Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study for 4 weeks before and for up to 10 weeks after the last dose of abatacept in such a manner that the risk of pregnancy is minimized.
4) Oral corticosteriod treatment must have been reduced to the equivalent of <= 10 mg prednisone daily for 28 days and stabilized for at least 25 out of 28 days prior to
treatment (Day 1). No intra-articular or IM injections of corticosteriods are permitted
within 28 days prior to treatment (Day 1).
5) At randomization, subjects receiving methotrexate monotherapy must have the following disease activity at randomization:
i) 10 or more swollen joints (66 joint count) and
ii) 12 or more tender joints (68 joint count) and
iii) C reactive protein (hsCRP) >= 0.8 mg/dL (result used from screening visit).
b) For subjects receiving methotrexate plus other DMARDs/Biologics (requiring washout):
At screening visit, subjects must have the following disease activity:
i) 6 or more swollen joints (66 joint count) and
ii) 8 or more tender joints (68 joint count) and
iii) no restriction on hsCRP
After washout, at randomization (Day 1), subjects must have the following disease activity:
i) 10 or more swollen joints (66 joint count) and
ii) 12 or more tender joints (68 joint count) and
iii) Creactive protein (hsCRP) >= 0.8 mg/dL (result used from screening or Day -3 visit).
6) Subjects must be willing to self-inject or allow a caregiver to do it for them.
7) Subjects must be able to adhere to the study visit schedule, understand, and comply with other protocol requirements.
1) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period b) Women who are pregnant or breastfeeding. c) Women with a positive pregnancy test on enrolment or prior to investigational product administration;2) Target Disease Exceptions
a) Subjects who meet diagnostic criteria for any other rheumatic disease (eg, lupus
erythematous).
b) Subjects with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules).;3) Medical History and Concurrent Diseases
b) 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.
c) Female subjects who have had a breast cancer screening study that is suspicious for malignancy, and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations (please refer to Section 6.3.6).
d) Subjects with a history of cancer within the last five years (other than nonmelanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to dosing. Subjects with carcinoma in situ, treated with definitive surgical intervention prior to study entry, are allowed.
e) Subjects who have clinically significant drug or alcohol abuse.
f) Subjects with any serious acute bacterial infection (such as pneumonia or pyelonephritis unless treated and completely resolved with antibiotics).
g) Subjects with severe chronic or recurrent bacterial infections (such as recurrent pneumonia, chronic bronchiectasis).
h) Subjects at risk for tuberculosis (TB). Specifically, subjects with:
i) Current clinical, radiographic or laboratory evidence of active or latent TB.
ii) A history of active TB within the last 3 years even if it was treated.
iii) A history of active TB greater than 3 years ago unless there is documentation
that the prior anti-TB treatment was appropriate in duration and type.
i) Subjects with herpes zoster that resolved less than 2 months prior to enrolment.
j) Subjects with evidence (as assessed by the investigator) of active or latent bacterial or viral infections at the time of potential enrolment, including subjects with evidence of Human Immunodeficiency Virus (HIV) infection
4) Physical and Laboratory Test Findings
a) Hepatitis B surface antigen-positive subjects.
b) Hepatitis C antibody-positive subjects who are also RIBA-positive or PCR positive.
c) Subjects with any of the following laboratory values:
i) Hgb < 8.5 g/dL.
ii) WBC < 3,000/mm3 (3 x 109/L)
iii)Platelets < 100,000/mm3 (100 x 109/L).
iv) Serum creatinine > 2 times upper limit of normal.
v) Serum ALT or AST > 2 times upper limit of normal.
vi) Any other laboratory test results that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.
6) Prohibited Treatments and/or Therapies
a) Subjects who have received treatment with rituximab.
b) Subjects who have had prior exposure to abatacept (Ctla4-Ig)
c) Subjects who have been exposed to any investigational drug or placebo or approved biological agent withi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method