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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02353780
Recruitment Status : Unknown
Verified August 2017 by Dr. Larry W. Moreland, University of Pittsburgh.
Recruitment status was:  Active, not recruiting
First Posted : February 3, 2015
Last Update Posted : June 3, 2019
Sponsor:
Collaborators:
Genentech, Inc.
Bristol-Myers Squibb
Information provided by (Responsible Party):
Dr. Larry W. Moreland, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE June 30, 2013
First Posted Date  ICMJE February 3, 2015
Last Update Posted Date June 3, 2019
Study Start Date  ICMJE March 2015
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 2, 2015)
Mechanistic Comparisons (changes in frequencies of peripheral blood immune cell subsets following institution of a subcutaneously administered TNF antagonist, tocilizumab or abatacept.) [ Time Frame: 6 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02353780 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2015)
  • Efficacy as measured by CDAI remission < 2.8 [ Time Frame: 3 month and 6 month ]
    Efficacy as measured by CDAI remission < 2.8
  • Efficacy as measured by DAS remission with a DAS28-CRP < 2.4 [ Time Frame: 3 month and 6 month ]
    Efficacy as measured by DAS remission with a DAS28-CRP < 2.4
  • Efficacy as measured by ACR20, 50, and 70 response [ Time Frame: 3 month and 6 month ]
    Efficacy as measured by ACR20, 50, and 70 response
  • Efficacy as measured by EULAR response [ Time Frame: 3 month and 6 month ]
    Efficacy as measured by EULAR response
  • Adherence to drug regimen [ Time Frame: 3 month and 6 month ]
    Adherence to drug regimen
  • Number of patients with steroid doses remaining below 10 mg/day [ Time Frame: 3 month and 6 month ]
    Number of patients with steroid doses remaining below 10 mg/day
  • Average corticosteroid dose [ Time Frame: 3 month and 6 month ]
    Average corticosteroid dose
  • Number of patients without additional oral DMARDs or with a reduction in the number of oral DMARDs [ 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 (side effects, lack of efficacy, cost, patient compliance, etc.) [ Time Frame: 3 month and 6 month ]
    Reason for discontinuation of treatment (side effects, lack of efficacy, cost, patient compliance, etc.)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mechanistic Studies of B- and T-Cell Function in RA Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept
Official Title  ICMJE Mechanistic Studies of B- and T-Cell Function in Rheumatoid Arthritis Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Basic Science
Condition  ICMJE Rheumatoid Arthritis (RA)
Intervention  ICMJE
  • Drug: TNF Antagonist (enbrel, humire, remicade, cimzia, symponi)
    TNF Antagonist; treating rheumatologist selects specifics for the therapy chosen.
    Other Names:
    • Enbrel
    • Humira
    • Remicade
    • Cimzia
    • Symponi
  • Drug: Abatacept
    Abatacept; SQ; specifics to be determined by the treating rheumatologist.
    Other Name: Orencia
  • Drug: Tocilizumab
    Tocilizumab; SQ; specifics determined by the treating rheumatologist.
    Other Name: Actemra
Study Arms  ICMJE
  • 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.
    Intervention: Drug: TNF Antagonist (enbrel, humire, remicade, cimzia, symponi)
  • Active Comparator: Abatacept
    The participant will be prescribed abatacept in this arm. The treating rheumatologist selects the appropriate options for that therapy.
    Intervention: Drug: Abatacept
  • Active Comparator: Tocilizumab
    The participant will be prescribed tocilizumab. The treating rheumatologist selects the appropriate options for that therapy.
    Intervention: Drug: Tocilizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Actual Enrollment  ICMJE
 (submitted: May 30, 2019)
10
Original Estimated Enrollment  ICMJE
 (submitted: February 2, 2015)
90
Estimated Study Completion Date  ICMJE July 2019
Estimated Primary Completion Date July 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
  • Any of the following hematologic abnormalities, confirmed by repeat tests:

    1. White blood count < 3,000/µL or > 14,000/µL
    2. Lymphocyte count <500/µL
    3. Platelet count < 100,000/µL
    4. Hemoglobin < 8.0 g/dL
    5. 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 64 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02353780
Other Study ID Numbers  ICMJE PRO10100422
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Dr. Larry W. Moreland, University of Pittsburgh
Study Sponsor  ICMJE Dr. Larry W. Moreland
Collaborators  ICMJE
  • Genentech, Inc.
  • Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Larry W. Moreland, MD University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date August 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP