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
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Condition or disease | Intervention/treatment | Phase |
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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 |
Allocation: | Randomized |
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 |

Arm | Intervention/treatment |
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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.
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Drug: TNF Antagonist (enbrel, humire, remicade, cimzia, symponi)
TNF Antagonist; treating rheumatologist selects specifics for the therapy chosen.
Other Names:
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Active Comparator: Abatacept
The participant will be prescribed abatacept in this arm. The treating rheumatologist selects the appropriate options for that therapy.
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Drug: Abatacept
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.
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Drug: Tocilizumab
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.)

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 64 Years (Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosis of RA by a physician as defined by the 1987 and/or 2010 ACR criteria.
- 18 years of age or less than or equal to 64 at the time of diagnosis of RA.
- RA Disease Activity CDAI > 10
- If using oral corticosteroids, must have been on stable dose (≤ 10 mg/day) for at least 2 weeks prior to study drug initiation.
- PPD negative or if PPD positive documentation of therapy with INH for at least 1 month prior to study initiation and negative chest x-ray.
- Must have been treated within the past year with either methotrexate (MTX), leflunomide (LEF), hydrochloroquine (HCQ) and/or sulfasalazine (SSZ) for ≥ 3 months.
- Prior or concurrent use of other oral DMARD therapy, including MTX, leflunomide, SSZ, and HCQ, is permitted. Patients taking oral DMARDs must be on stable doses of DMARDs for at least 4 weeks prior to study drug initiation. Subjects are not required to be taking an oral DMARD.
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.
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Any of the following hematologic abnormalities, confirmed by repeat tests:
- White blood count < 3,000/µL or > 14,000/µL
- Lymphocyte count <500/µL
- Platelet count < 100,000/µL
- Hemoglobin < 8.0 g/dL
- Neutrophil count < 2,000 cells/µL
- 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

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 |
Documents provided by Dr. Larry W. Moreland, University of Pittsburgh:
Responsible Party: | Dr. Larry W. Moreland, Chief, Division of Rheumatology and Clinical Immunology, University of Pittsburgh |
ClinicalTrials.gov Identifier: | NCT02353780 |
Other Study ID Numbers: |
STUDY19040127 |
First Posted: | February 3, 2015 Key Record Dates |
Results First Posted: | October 1, 2020 |
Last Update Posted: | October 1, 2020 |
Last Verified: | September 2020 |
Rheumatoid arthritis TNF inhibitors |
Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Etanercept Abatacept Infliximab Certolizumab Pegol |
Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Gastrointestinal Agents Immunosuppressive Agents Immunologic Factors Dermatologic Agents |