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Mechanistic Studies of Teriflunomide in RRMS

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ClinicalTrials.gov Identifier: NCT03464448
Recruitment Status : Completed
First Posted : March 14, 2018
Last Update Posted : December 27, 2022
Sponsor:
Information provided by (Responsible Party):
Yang Mao-Draayer, University of Michigan

Study Description
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Brief Summary:
This study is to address the mechanism of action of teriflunomide in a phase IV open label trial with Teriflunomide in multiple sclerosis. Researchers will recruit 20 relapsing remitting multiple sclerosis patients (Group 1) start on treatment with teriflunomide (Aubagio). Patients will be enrolled from the Multiple Sclerosis Center at the University of Michigan Health System in Ann Arbor. Meanwhile, 10 healthy controls will be recruited, to establish a healthy baseline for B and T cells, which are affected by both MS and its treatment (Group 2). This Study will collect baseline pre-treatment blood samples periodically for up to 2 years. Blood biomarker changes will be correlated with clinical response to teriflunomide treatment intervention.

Condition or disease Intervention/treatment
Relapsing Remitting Multiple Sclerosis Drug: Teriflunomide

Detailed Description:

Multiple sclerosis is the most common autoimmune inflammatory and debilitating chronic demyelinating disease of the central nervous system mainly affecting young adults. There is a tremendous need to understand the mechanism of action of the treatment and how they might work in multiple sclerosis patients. Most recently, teriflunomide (AubagioTM) has been demonstrated to act as an immune modulatory therapy for patients with multiple sclerosis. Although one biochemical mechanism of action is understood to be related to inhibition of dihydroorotate dehydrogenase (DHODH) which affects synthesis of pyrimidine nucleotides, there have also been reports that the functions of regulatory T cells are promoted by these drugs independent of DHODH. Much accumulating evidence suggests that specialized subsets of B lymphocytes are important inducers of regulatory T cells, as well as having killer functions that may preferentially target TH1 and TH17 cells.

This study aims to address the mechanism of action of teriflunomide in a phase IV open label trial with Teriflunomide in multiple sclerosis

Study Design
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Study Type : Observational
Actual Enrollment : 30 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Mechanistic Studies of Teriflunomide in Relapsing Remitting Multiple Sclerosis: Regulatory B Lymphocytes as Central Mediators of the Therapeutic Effects of Teriflunomide in MS
Actual Study Start Date : April 17, 2018
Actual Primary Completion Date : October 13, 2021
Actual Study Completion Date : October 13, 2021

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
1
Patients with RRMS who have been newly prescribed Teriflunomide.
 Drug: Teriflunomide
AUBAGIO® (teriflunomide) is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS), which inhibits pyrimidine de novo synthesis by blocking the enzyme dihydroorotate dehydrogenase.
Other Name: Aubagio
2
Healthy Controls


Outcome Measures
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Primary Outcome Measures :
  1. Changes in frequency of regulatory and effector B cell subset [ Time Frame: From baseline to 6 months and 12 months ]
    Compare aubagio treatment to baseline and to healthy controls


Secondary Outcome Measures :
  1. Change in frequency of CD4+ Th17, Th1, Th2, and Treg cells [ Time Frame: From baseline to 6 months and 12 months ]
    Compare aubagio treatment to baseline and to healthy controls

  2. Change in chemokine levels [ Time Frame: From baseline to 6 months and 12 months ]
    Compare aubagio treatment to baseline and to healthy controls

  3. Change in cytokine levels [ Time Frame: From baseline to 6 months and 12 months ]
    Compare aubagio treatment to baseline and to healthy controls


Biospecimen Retention:   Samples Without DNA
Blood will be collected after 3, 6, 9, 12, 18 and 24 months of treatment.

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
A total of 20 multiple sclerosis (MS) patients and 10 healthy controls will be recruited to voluntarily donate blood for the study. Blood samples will be collected prior to starting teriflunomide treatment (baseline) and after 3, 6, 9, 12, 18 and 24 months of treatment (+/- 2 weeks).
Criteria

Inclusion Criteria:

  1. Patients with clinically-defined relapsing-remitting MS (RRMS) who " are newly starting on teriflunomide (AubagioTM) at the time of enrollment " have no evidence of relapse or corticosteroid treatment use within 2 months prior to enrollment

    OR

    Healthy controls who do not have a significant medical condition such as cancer, chronic infection, or autoimmune disease, have not taken steroids in the past 2 months, and who are not on an immune suppressant medication.

  2. Ability to give informed consent
  3. Willing to have blood drawn as scheduled in the protocol
  4. Willing and able to complete all procedures and evaluations related to the study

Exclusion Criteria:

  1. Medical or psychiatric conditions that may affect the patient's ability to give informed consent
  2. Has received an experimental drug within 30 days of enrollment

  3. Concomitant other disease modifying medications (such as Rebif, Betaseron, Avonex, Copaxone, Gilenya, Tecfidera, Alemtuzumab, methotrexate, azathioprine, mitoxantrone, cyclophosphamide, cyclosporine, natalizumab, rituxan, ocrelizumab, etc.) without the minimal washout period stated below:

    " rebif, betaseron, avonex, copaxone within 1 month " zinbryta, plegridy, gilenya, tecfidera within 2 months " natalizumab within 3 months " immunosuppressive/chemotherapeutic medications (e.g. azathioprine, methotrexate) within 6 months " cyclophosphamide within 1 year " rituximab, ofatumumab, ocrelizumab, cladribine within 1 year " alemtuzumab at any time " any mitoxantrone during previous 2 years prior to randomization or evidence of cardiotoxicity following mitoxantrone or a cumulative life-time dose of more than 60 mg/m2 " lymphoid irradiation, bone marrow transplantation or other immunosuppressive treatments with effects potentially lasting over 6 months, at any time

  4. Has any contraindication to high-dose immunotherapy, including pregnancy, trying to become pregnant, or breast feeding during the study.
Contacts and Locations
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Information from the National Library of Medicine

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): NCT03464448


Locations
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United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
Investigators
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Principal Investigator: Yang Mao-Draayer, MD/PHD University of Michigan
More Information
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Publications:

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Responsible Party: Yang Mao-Draayer, Professor of Neurology, University of Michigan
ClinicalTrials.gov Identifier: NCT03464448    
Other Study ID Numbers: HUM00136966
First Posted: March 14, 2018    Key Record Dates
Last Update Posted: December 27, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Yang Mao-Draayer, University of Michigan:
Teriflunomide
B cell
T cell
cytokines
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Teriflunomide
 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
Immunosuppressive Agents
Immunologic Factors