Mechanistic Studies of Teriflunomide in RRMS

Completed

• Conditions: Relapsing Remitting Multiple Sclerosis
• Interventions: Drug: Teriflunomide

• Registration Number: NCT03464448
• Lead Sponsor: University of Michigan

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.

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 Timeline

• Study First Submitted: 2018-03-07
• Study First Submitted QC: 2018-03-07
• Study First Posted: 2018-03-14
• Study Start: 2018-04-17
• Primary Completion: 2021-10-13
• Study Completion: 2021-10-13
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-23
• Last Update Posted: 2022-12-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
1	Teriflunomide	Patients with RRMS who have been newly prescribed Teriflunomide.

Primary Outcome Measures

Name	Time	Method
Changes in frequency of regulatory and effector B cell subset	From baseline to 6 months and 12 months	Compare aubagio treatment to baseline and to healthy controls

Secondary Outcome Measures

Name	Time	Method
Change in cytokine levels	From baseline to 6 months and 12 months	Compare aubagio treatment to baseline and to healthy controls
Change in frequency of CD4+ Th17, Th1, Th2, and Treg cells	From baseline to 6 months and 12 months	Compare aubagio treatment to baseline and to healthy controls
Change in chemokine levels	From baseline to 6 months and 12 months	Compare aubagio treatment to baseline and to healthy controls

Trial Locations

Locations (1)

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States