A Phase IIIB, Multi-Center, Randomized, Double Blind, Study to Evaluate Remission and Joint Damage Progression in Methotrexate Naive Early Erosive RA Subjects Treated with Abatacept Plus Methotrexate Compared with Methotrexate. Revised Protocol 04, incorporating Protocol Amendments 05, 06, 08, 09 (V1.0 dated 18-Nov-2008) and Administrative Letter 02. Pharmacogenetics Amendment 1 dated 16-May-2005. Protocol Amendments 3 & 4 - Site Specific - dated 28-Dec-2005. And Protocol Amendment 07 - Site Specific (v2.0, date 27-Jul-2007).
- Conditions
- Rheumatoid Arthritis, Nos
- Registration Number
- EUCTR2005-000784-26-BE
- Lead Sponsor
- Bristol Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 750
1) Subject is willing to participate in the study and has signed the informed consent.
2) Males or females (not nursing and not pregnant) = 18 years of age. Males and
women of child-bearing potential are eligible if they are practicing effective
contraceptive measures.
3) Subjects must meet the criteria of the American Rheumatism Association (1987) for
the diagnosis of rheumatoid arthritis.
4) Subjects must have a diagnosis of RA less than or equal to 2 years.
5) Subjects must have high disease activity as defined by a tender joint count of at least 12, swollen joint count of at least 10, and a CRP of = .45 mg/dL or = 4.5 mg/L.
6) Subjects that are RF or anti-CCP positive.
7) Subjects must have evidence of erosion of the hands, wrists or feet on the screening radiograph. (To be read centrally)
8) Subjects must be methotrexate naive or their prior exposure must have been =10mg a week for not more than 3 weeks and no dose for 3 months prior to signing the informed consent.
9) Men and women (not nursing and not pregnant) = 18 years of age. Men and Women of childbearing potential are eligible if they are practicing effective contraceptive measures.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity
25 IU/L or equivalent units of HCG) within 48 hours prior to the start of study
medication.
Male subjects must be using an adequate method of contraception throughout the study including up to 10 weeks after the last infusion of abatacept so that the risk of pregnancy to their partner is minimized.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 10 weeks after the last infusion of abatacept.
2) Subjects who are impaired, incapacitated, or incapable of completing study related
assessments.
3) Subjects who meet diagnostic criteria for any other rheumatic disease (e.g., lupus
erythematous).
4) Subjects who have previously received treatment with an approved or investigational biologic RA therapy (infliximab, etanercept, anakinra, adalimumab).
5) Subjects with active vasculitis of a major organ system with the exception of
rheumatoid nodules.
6) Subjects with current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, or other medical conditions that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.
7) Female subjects, who have not had age and/or risk factor appropriate breast cancer screening or 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 7.3.2).
8) Subjects with a history of cancer within the last five years (other than non-melanoma skin cell cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed prior to dosing.
9) Subjects who have clinically significant drug or alcohol abuse.
10) Subjects with any serious acute bacterial infection (such as pneumonia or
pyelonephritis) unless treated and completely resolved with antibiotics.
11) Subjects with severe chronic or recurrent bacterial infections (such as recurrent
pneumonia, chronic bronchiectasis).
12) The following subjects are excluded from this study:
- Subjects with current clinical or laboratory evidence of active or latent
tuberculosis (TB).
- Subjects with a history of active TB that was treated within the last 3 years.
- Subjects with 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.
13) Subjects with herpes zoster that resolved less than 2 months prior to enrollment.
14) 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.
15) Subjects with Hepatitis B surface antigen.
16) Subjects with Hepatitis C antibody-positive subjects who are also RIBA-positive or PCR-positive.
17) Subjects with any of the following laboratory values:
- Hgb < 8.5 g/dL.
- WBC < 3,000/mm3 (3 x 109/L)
- Platelets < 100,000/mm3 (100 x 109/L).
- Serum creatinine > 2 times upper limit of normal.
- Serum ALT or AST > 2 times upper limit of normal.
- Any other laboratory test results that, in the opinion of the investigator, might place
the subject at unacceptable risk for participation in this study.
18) Subjects with a history of intolerance to methotrexate.
19) Subjects who have at any time received treatment with CTLA4Ig, BMS-188667
(abatacept).
20) Subjects who have received treatment with any investigational drug within 28 days (or less than 5 terminal half-lives of elimination) of the Day 1 dose.
21) Subjects currently receiving treatment with leflunomide, m
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method