Status and phase
Conditions
Treatments
About
An Agency for Healthcare Research and Quality executive summary indicated that better comparative effectiveness trial designs are needed to determine the relative merits of existing versus new and expensive biologic drug therapies for rheumatoid arthritis (RA). There are now 9 biologic therapies approved for treating RA. Four classes of biologics (TNF antagonists, B-cell inhibitors, T-cell co-stimulator blocker, and Interleukin-6 receptor blocker) are approved for use in RA patients with moderate or severe disease activity. Several critical questions have arisen, such as 1) what therapy should be prescribed after failure of methotrexate and/or other oral disease modifying antirheumatic drugs (DMARDs) to adequately control disease activity; 2) what is the level of efficacy of the various biologic therapies when compared in head-to-head trials; and 3) what are the mechanisms associated with failure of methotrexate and/or other oral DMARD therapy and responsiveness to biologic therapies. The MAZERATI study will provide the foundation for answering these questions and determining the mechanisms associated with these biologic therapies.
Full description
Single center, randomized, assessor-blinded, observational longitudinal assessment. Subjects will be randomized to treatment with an anti-TNF therapy, tocilizumab or abatacept and evaluated at baseline, and after 1, 3 and 6 months of therapy. All biologics will be administered subcutaneously (SQ). A blinded assessor will perform clinical disease activity assessments and blood samples will be obtained for mechanistic studies.
After randomization, patients must take at least one dose of the assigned medication and must maintain their baseline prednisone and oral disease modifying anti-rheumatic drug (DMARD) medications until they have received their first dose of assigned medication to be considered per protocol participants. During the first 3 months of therapy, patients and their physicians will be permitted to taper but not increase corticosteroids. Adjustments of study medication or oral DMARDs will not be permitted during the first 3 months of the study except as outlined in the protocol. Adjustments or additions of analgesics will be permitted throughout the study period.
Following randomization and treatment initiation, study participants will be seen in the clinic at 1 month (3-5 weeks), 3 months (10-14 weeks), and 6 months (22-30 weeks) after the initiation of therapy; at each time point, a blinded clinical disease activity assessment will occur and blood samples will be obtained for mechanistic studies. The occurrence and severity of unanticipated problems will be recorded continuously throughout the study.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Exclusion criteria
Use of cyclophosphamide, penicillamine, cyclosporine A, tacrolimus or gold therapy is not permitted in the 6 months prior to enrollment.
Patients who are using or have used other biologic agents or tofacitinib concomitantly or prior to this study
History of active and/or chronic infection such as hepatitis, pneumonia, pyelonephritis,herpetic infections or chronic skin infections and any active opportunistic infection, including but not limited to evidence of active cytomegalovirus, active Pneumocystis carinii, aspergillosis, histoplasmosis or atypical mycobacterium infection.
Active TB or evidence of latent TB (positive PPD skin test or a history of old or latent TB on chest x-ray) without adequate therapy for TB.
Pregnant or lactating women.
Patients with current signs or symptoms of uncontrolled renal, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease.
Diagnosis of liver disease or elevated hepatic enzymes, as defined by ALT, AST or both >1.5 x the upper limit of normal (ULN) or total bilirubin > ULN.
Any of the following hematologic abnormalities, confirmed by repeat tests:
Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
Immunization with a live/attenuated vaccine within 2 months prior to baseline or 3 months of last study visit.
History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
Patients with reproductive potential not willing to use an effective method of contraception
History of alcohol, drug or chemical abuse with 1 year prior to screening
Primary purpose
Allocation
Interventional model
Masking
10 participants in 3 patient groups
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal