NCT02353780

Mechanistic Studies of B- and T-Cell Function in RA Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept

Mechanistic Studies of B- and T-Cell Function in Rheumatoid Arthritis Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept

• Status: Terminated
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Dr. Larry W. Moreland · Academic / Other
• Sex: All
• Age: 18 Years – 64 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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.

Conditions

• Rheumatoid Arthritis (RA)

Interventions

Type	Name	Description
DRUG	TNF Antagonist (enbrel, humire, remicade, cimzia, symponi)	TNF Antagonist; treating rheumatologist selects specifics for the therapy chosen.
DRUG	Abatacept	Abatacept; SQ; specifics to be determined by the treating rheumatologist.
DRUG	Tocilizumab	Tocilizumab; SQ; specifics determined by the treating rheumatologist.

Timeline

• Start date: 2015-03-01
• Primary completion: 2017-12-30
• Completion: 2018-11-30
• First posted: 2015-02-03
• Last updated: 2020-10-01
• Results posted: 2020-10-01

Locations

1 site across 1 country: United States