Mechanistic Studies of B- and T-Cell Function in RA Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept (MAZERATI)
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|ClinicalTrials.gov Identifier: NCT02353780|
Recruitment Status : Terminated (Low enrollment)
First Posted : February 3, 2015
Results First Posted : October 1, 2020
Last Update Posted : October 1, 2020
|Condition or disease||Intervention/treatment||Phase|
|Rheumatoid Arthritis (RA)||Drug: TNF Antagonist (enbrel, humire, remicade, cimzia, symponi) Drug: Abatacept Drug: Tocilizumab||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Primary Purpose:||Basic Science|
|Official Title:||Mechanistic Studies of B- and T-Cell Function in Rheumatoid Arthritis Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept|
|Study Start Date :||March 2015|
|Actual Primary Completion Date :||December 30, 2017|
|Actual Study Completion Date :||November 30, 2018|
Active Comparator: Different TNF inhibitor
The participant will be prescribed any TNF antagonist in this arm. The treating rheumatologist selects the TNF antagonist and the appropriate options for that therapy.
Drug: TNF Antagonist (enbrel, humire, remicade, cimzia, symponi)
TNF Antagonist; treating rheumatologist selects specifics for the therapy chosen.
Active Comparator: Abatacept
The participant will be prescribed abatacept in this arm. The treating rheumatologist selects the appropriate options for that therapy.
Abatacept; SQ; specifics to be determined by the treating rheumatologist.
Other Name: Orencia
Active Comparator: Tocilizumab
The participant will be prescribed tocilizumab. The treating rheumatologist selects the appropriate options for that therapy.
Tocilizumab; SQ; specifics determined by the treating rheumatologist.
Other Name: Actemra
- Mechanistic Comparisons (Changes in Frequencies of Peripheral Blood Immune Cell Subsets Following Institution of a Subcutaneously Administered TNF Antagonist, Tocilizumab or Abatacept.) [ Time Frame: 0 to 3 months ]There will be no primary efficacy endpoints for the study. The primary endpoint of the study will be changes in frequencies of peripheral blood immune cell subsets following institution of a subcutaneously administered TNF antagonist, tocilizumab or abatacept. Flow ctyometry was performed on peripheral blood T cells to determine frequency of Th17/TfH cells based on cell surface markers.
- Efficacy (CDAI) [ Time Frame: 0 to 3 months ]Efficacy of therapy, as measured by number of participants with Clinical Disease Activity Index (CDAI) of less than 2.8 (remission). CDAI is a composite score of RA disease activity based on patient survey (up to 10 points), physician survey (up to 10 points), + number of swollen joints + number of tender joints. 0 = no disease, max score is 60, higher score = more severe disease. Number of patients achieving remission is reported.
- Efficacy (DAS) [ Time Frame: 3 month and 6 month ]Efficacy as measured by DAS remission with a DAS28-CRP < 2.4
- ACR20, 50, and 70 Response [ Time Frame: 3 month and 6 month ]Efficacy as measured by ACR20, 50, and 70 response at 3 months and 6 months versus baseline
- Efficacy (EULAR) [ Time Frame: 3 month and 6 month ]Efficacy as measured by European League against rheumatism (EULAR) response
- Adherence [ Time Frame: 3 month and 6 month ]Adherence to drug regimen over course of clinical study
- Steroid Use [ Time Frame: 3 month and 6 month ]Number of patients with steroid doses remaining below 10 mg/day
- Corticosteroid Use [ Time Frame: 3 month and 6 month ]Average corticosteroid dose
- DMARD Use [ Time Frame: 3 month and 6 month ]Number of patients without additional oral DMARDs or with a reduction in the number of oral DMARDs
- Reason for Discontinuation of Treatment [ Time Frame: 3 month and 6 month ]Reason for discontinuation of treatment as provided by patient/provider (side effects, lack of efficacy, cost, patient compliance, etc.)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02353780
|United States, Pennsylvania|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15261|
|Principal Investigator:||Larry W. Moreland, MD||University of Pittsburgh|