Rheumatoid Arthritis (RA)Phase 4MAZERATINCT02353780
Mechanistic Studies of B- and T-Cell Function in RA Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept
A Phase 4 study testing TNF Antagonist (enbrel, humire, remicade, cimzia, symponi), Abatacept and Tocilizumab in people with Rheumatoid Arthritis (RA), run by Dr. Larry W. Moreland at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Rheumatoid Arthritis (RA)
- What is being tested?
- TNF Antagonist (enbrel, humire, remicade, cimzia, symponi), Abatacept and Tocilizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to 30 Nov 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 19Show fewer
- 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:
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
About this study
Official title: Mechanistic Studies of B- and T-Cell Function in Rheumatoid Arthritis Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept
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.
Read the 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)
- Being tested
- TNF Antagonist (enbrel, humire, remicade, cimzia, symponi), Abatacept, Tocilizumab
- Keywords
- Rheumatoid arthritis, TNF inhibitors
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TNF Antagonist (enbrel, humire, remicade, cimzia, symponi)Drug
Also called Enbrel, Humira, Remicade, Cimzia
TNF Antagonist; treating rheumatologist selects specifics for the therapy chosen.
AbataceptDrug
Also called Orencia
Abatacept; SQ; specifics to be determined by the treating rheumatologist.
TocilizumabDrug
Also called Actemra
Tocilizumab; SQ; specifics determined by the treating rheumatologist.
| Study group | Role | What they receive |
|---|---|---|
| Different TNF inhibitor | Active comparator | 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. Receives: Drug: TNF Antagonist (enbrel, humire, remicade, cimzia, symponi) |
| Abatacept | Active comparator | The participant will be prescribed abatacept in this arm. The treating rheumatologist selects the appropriate options for that therapy. Receives: Drug: Abatacept |
| Tocilizumab | Active comparator | The participant will be prescribed tocilizumab. The treating rheumatologist selects the appropriate options for that therapy. Receives: Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mechanistic Comparisons (Changes in Frequencies of Peripheral Blood Immune Cell Subsets Following Institution of a Subcutaneously Administered TNF Antagonist, Tocilizumab or Abatacept.)
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.
Measured: 0 to 3 months
Secondary outcomes (9)
Efficacy (CDAI)
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.
Measured: 0 to 3 months
Efficacy (DAS)
Efficacy as measured by DAS remission with a DAS28-CRP < 2.4
Measured: 3 month and 6 month
ACR20, 50, and 70 Response
Efficacy as measured by ACR20, 50, and 70 response at 3 months and 6 months versus baseline
Measured: 3 month and 6 month
Efficacy (EULAR)
Efficacy as measured by European League against rheumatism (EULAR) response
Measured: 3 month and 6 month
Adherence
Adherence to drug regimen over course of clinical study
Measured: 3 month and 6 month
Steroid Use
Number of patients with steroid doses remaining below 10 mg/day
Measured: 3 month and 6 month
Corticosteroid Use
Average corticosteroid dose
Measured: 3 month and 6 month
DMARD Use
Number of patients without additional oral DMARDs or with a reduction in the number of oral DMARDs
Measured: 3 month and 6 month
Reason for Discontinuation of Treatment
Reason for discontinuation of treatment as provided by patient/provider (side effects, lack of efficacy, cost, patient compliance, etc.)
Measured: 3 month and 6 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2015 (estimated)
- Study startMar 2015
- Primary completion30 Dec 2017
- Study completion30 Nov 2018
Why it stopped: Low enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rheumatoid Arthritis (RA)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Larry W. Moreland
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Dr. Larry W. Moreland, University of Pittsburgh
- Investigators
- Larry W. Moreland, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02353780
- Sponsor's protocol ID
- STUDY19040127
- Acronym
- MAZERATI
- Status last verified
- Sep 2020
- First submitted
- 30 Jun 2013
- Last updated
- 1 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Studies of B- and T-Cell Function in Rheumatoid Arthritis Patients Treated With TNF Antagonists, Tocilizumab, or Abatacept
- ClinicalTrials.gov ID
- NCT02353780
- Acronym / sponsor ID
- MAZERATI / STUDY19040127
- Conditions
- Rheumatoid Arthritis (RA)
- Keywords
- Rheumatoid arthritis, TNF inhibitors
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollment
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Dr. Larry W. MorelandUniversity, hospital or other
- Collaborators
- Genentech, Inc., Bristol-Myers Squibb
- Study start
- Mar 2015
- Primary completion
- 30 Dec 2017 (actual)
- Study completion
- 30 Nov 2018 (actual)
- First posted
- 3 Feb 2015 (estimated)
- Results
- Posted 1 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Different TNF inhibitor | Active comparator | Drug: TNF Antagonist (enbrel, humire, remicade, cimzia, symponi)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. |
| Abatacept | Active comparator | Drug: AbataceptThe participant will be prescribed abatacept in this arm. The treating rheumatologist selects the appropriate options for that therapy. |
| Tocilizumab | Active comparator | Drug: TocilizumabThe participant will be prescribed tocilizumab. The treating rheumatologist selects the appropriate options for that therapy. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TNF Antagonist (enbrel, humire, remicade, cimzia, symponi)Also: Enbrel, Humira, Remicade, CimziaTNF Antagonist; treating rheumatologist selects specifics for the therapy chosen. | Drug | Different TNF inhibitor |
| AbataceptAlso: OrenciaAbatacept; SQ; specifics to be determined by the treating rheumatologist. | Drug | Abatacept |
| TocilizumabAlso: ActemraTocilizumab; SQ; specifics determined by the treating rheumatologist. | Drug | Tocilizumab |
Primary outcome
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.
9 secondary outcomes
Efficacy (CDAI)
Time frame: 0 to 3 months
Efficacy (DAS)
Time frame: 3 month and 6 month
ACR20, 50, and 70 Response
Time frame: 3 month and 6 month
Efficacy (EULAR)
Time frame: 3 month and 6 month
Adherence
Time frame: 3 month and 6 month
Steroid Use
Time frame: 3 month and 6 month
Corticosteroid Use
Time frame: 3 month and 6 month
DMARD Use
Time frame: 3 month and 6 month
Reason for Discontinuation of Treatment
Time frame: 3 month and 6 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Rheumatoid Arthritis (RA)
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Active, not recruitingObservational study
Overactive Bladder Symptoms and Urinary Incontinence In Women With Rheumatoid Arthritis
Rheumatoid Arthritis, Rheumatoid Arthritis (RA)
Recruiting
GenAI-Assisted Rheumatoid Arthritis Bone Erosion Risk Assessment and DMARD Selection
Rheumatoid Arthritis
Not yet recruitingObservational study
The Impact of Rheumatoid Arthritis Treatments on the Modulation of Extracellular Vesicles and Other Biomarkers Involved in the Development of Lung Cancer
Rheumatoid Arthritis (RA), Lung Neoplasms
Not yet recruiting
MYTP01 for Immune-Mediated Diseases
IgA Nephropathy, Kidney Transplant Recipients
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Larry W. Moreland, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing TNF Antagonist (enbrel, humire, remicade, cimzia, symponi), Abatacept and Tocilizumab in people with Rheumatoid Arthritis (RA), run by Dr. Larry W. Moreland at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2020.