A randmized double blind trial to evaluate efficacy and safety of SAR153191 on top of methotrexate in patients with active Rheumatoid arthritis
- Conditions
- Health Condition 1: null- Rheumatoid ArthritisHealth Condition 2: M069- Rheumatoid arthritis, unspecified
- Registration Number
- CTRI/2012/05/002630
- Lead Sponsor
- Sanofi
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 1116
I 01. Diagnosis of rheumatoid arthritis (RA) as defined by the 1987 revised American College
of Rheumatology (ACR) criteria with disease duration of no less than 3 months and ACR
class I-III (see Appendix A).
I 02. Patients must be on a stable dose of MTX (10 to 25 mg/week) for a minimum of 6 weeks
prior to the Screening Visit, except patients within of the Asia-Pacific Region (Taiwan,
South Korea, Malaysia, Philippines, Thailand, and India) are allowed to use a stable dose
of MTX between 6 to 25 mg/week for a minimum of 6 weeks prior to the Screening Visit.
Patients must intend to continue the stable dose of MTX for the duration of the study
I 03. Patients must have been treated with, and tolerated, a minimum of 12 weeks treatment with
methotrexate (MTX) prior to the randomization visit.
I 04. Patient with moderate to severe active disease defined as:
- At least 8 out of 68 joints assessed as painful or tender on motion at both screening and
baseline visits, and
- At least 6 out of 66 joints assessed as swollen at both screening and baseline visits, and
- hs C-reactive protein >6 mg/L ( >0.6 mg/dL) at screening visit.
I 05
- At least 1 locally documented bone erosion (on X-ray) prior to first IMP
administration, or
- Anti CCP antibody positive according to screening laboratory tests, or
- Positive rheumatoid factor according to screening laboratory tests.
I 06. Having signed a written informed consent prior to any procedure related to the study.
E 01. Male or female 18 years of age or 75 years of age.
E 02. Autoimmune disease other than RA or significant systemic involvement (vasculitis,
pulmonary fibrosis, Feltyâ??s syndrome).
E 03. History of chronic, or recurrent, and current acute inflammatory joint disease other than
RA, or RA diagnosed before the age of 16.
E 04. Treatment with oral prednisone or equivalent 10 mg per day within 4 weeks prior to the
randomization visit or use of parenteral or intra-articular glucocorticosteroids within 4
weeks prior to the Screening Visit.
E 05. Start treatment or change dose of current treatment with NSAIDs/COX2 inhibitors or oral
corticosteroids for 4 weeks prior to baseline.
E 06. Current treatment with DMARDS/immunosuppressive agents other than MTX:
cyclosporine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine or
hydroxychloroquine within 4 weeks prior to the Screening Visit or azathioprine,
cyclophosphamide within 12 weeks prior to the Screening Visit or leflunomide within 12
weeks prior to the Screening Visit (or 4 weeks after 11 days of standard cholestyramine
washout).
E 07. Past history of nonresponse to prior therapy with TNF antagonist or a biologic treatment.
E 08. Prior therapy with a TNF antagonist or any other biologic agents within 3 months prior to
randomization.
E 09. Administration of an investigational drug or therapy within 60 days or at least 5 half-lives,
whichever is longer, of the investigational drug, prior to the Screening Visit.
E 10. History of malignancy other than carcinoma in-situ of the cervix, or adequately treated,
nonmetastatic squamous or basal cell carcinoma of the skin within five years prior to
Screening Visit. History of lymphoproliferative disease or possible current
lymphoproliferative disease.
E 11. History of alcohol or drug abuse within the 5 years prior to the Screening Visit.
E 12. Have a history or presence of significant other concomitant illness according to the
Investigator judgment such as, but not limited to cardiovascular (including stage III or IV
cardiac failure according to New York Heart Association (NYHA) classification), renal,
neurological, endocrinological, gastrointestinal, hepatic disease, metabolic, pulmonary or
lymphatic disease that would adversely affect the subjectâ??s participation in this study.
E 13. Conditions/situations such as: Patients with short life expectancy
- Patients with conditions/concomitant diseases making them nonevaluable for the
primary efficacy endpoint
- Requirement for concomitant treatment that could bias primary evaluation
- Impossibility to meet specific protocol requirements (eg, need for hospitalization, etc)
- Patient is the Investigator or any subinvestigator, research assistant, pharmacist, study
coordinator, other staff or relative thereof directly involved in the conduct of the
protocol
- Uncooperative or any condition that could make the patient potentially noncompliant
with the study procedures
Exclusion criteria related to the active comparator and/or mandatory background
therapies
E 14. Patients not willing to take folic acid with the MTX dose, to minimize toxicity.
Exclusion criteria related to the current knowledge o
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Percentage of patients who achieved ACR20 at Week 24Timepoint: Wk 24
- Secondary Outcome Measures
Name Time Method â?¢Change in modified Van der Heijde Sharp score at Week 52 (composite index on X-ray assessed through central reading). <br/ ><br>â?¢Change in physical function as measured by the change from baseline in the Health Assessment Question-Disability (HAQ-DI) at Week 52. <br/ ><br>â?¢Percentage of patients who achieved and maintained (for at least 6 months) an ACR70 response. <br/ ><br>Timepoint: Wk 52