Biomarkers and Disease Activity in Patients Treated With Teriflunomide (Aubagio)

NCT03561402 | Completed FDA Drug

• 1 other identifier: GZ-2015-11483
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a two-year prospective observational study of patients treated with teriflunomide. The investigators will recruit up to 75 patients at baseline, based on the estimate that approximately 20% of these patients (\~ 15 patients) will have evidence of disease activity at the end of the first year of treatment with teriflunomide, as determined by clinical evaluation (relapses) and MRI activity (new T2 hyperintense lesions). The investigators will assess the expression of a putative biomarker signature consisting of toll like receptor 2(TLR2), TLR4 and chemokine receptor 1 (CCR1) on CD4 T-subsets at baseline and at intervals on treatment with teriflunomide to determine whether expression of this biomarker signature on one or more CD4 T-subsets correlates with disease activity.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

biomarker; teriflunomide; activity

Outcome Measures

Primary Outcomes (1)

• Biomarkers and disease activity in patients treated with Teriflunomide (Aubagio)

  Primary outcome measure * Membrane expression of TLR2, TLR4 and CCR1 Percent expression and mean fluorescence intensity in CD4 T-cell subsets in active vs. stable patient groups * TOB1 expression by real-time PCR on CD4 T-cell subsets Number of molecules per µg cDNA * PrimeFLow assay Number of T-cells expressing both mRNA and surface membrane TLR2 Number of T-cells expressing mRNA for TOB1 Number of T-cells expressing mRNA for TOB 1 and surface protein for TLR2

  26 months

Study Arms (2)

Patients with active disease

From the cohort of patients receiving teriflunomide - 1 tablet (14 mg) daily, the investigators will identify patients that have active disease..

Drug: Teriflunomide

Patients with stable disease

From the cohort of patients receiving teriflunomide (as above), the investigators will identify patients that have stable disease.

Drug: Teriflunomide

Interventions

Teriflunomide DRUG

Each patient will receive 1 tablet (14 mg) on a daily basis.

Also known as: Aubagio

Patients with active disease; Patients with stable disease

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients with relapsing-remitting MS who agree to be treated with teriflunomide

You may qualify if:

• Treatment naive patients with relapsing-remitting multiple sclerosis
• Patients treated previously with one or more previous disease-modifying treatments but with a washout period of at least 4 weeks before starting treatment with teriflunomide.

You may not qualify if:

• Acute infections in the preceding 4 weeks
• Vaccination in the previous 2 months
• An active malignancy (except basal cell carcinoma)
• Pregnant or breastfeeding patients
• Communication difficulty, i.e. unable to understand the study
• Vulnerable patients, i.e. unable to provide informed consent or lacking legal freedom, e.g. prisoners

Sponsors & Collaborators

• McGill University: lead

Study Sites (1)

Department of Pathology

Montreal, Quebec, H3A 2B4, Canada

Location

Related Publications (4)

• Kieseier BC, Wiendl H. New evidence for teriflunomide in multiple sclerosis. Lancet Neurol. 2014 Mar;13(3):234-5. doi: 10.1016/S1474-4422(14)70012-2. Epub 2014 Jan 23. No abstract available.

  PMID: 24461573 BACKGROUND

• Zastepa E, Fitz-Gerald L, Hallett M, Antel J, Bar-Or A, Baranzini S, Lapierre Y, Haegert DG. Naive CD4 T-cell activation identifies MS patients having rapid transition to progressive MS. Neurology. 2014 Feb 25;82(8):681-90. doi: 10.1212/WNL.0000000000000146. Epub 2014 Jan 22.

  PMID: 24453076 BACKGROUND

• Corvol JC, Pelletier D, Henry RG, Caillier SJ, Wang J, Pappas D, Casazza S, Okuda DT, Hauser SL, Oksenberg JR, Baranzini SE. Abrogation of T cell quiescence characterizes patients at high risk for multiple sclerosis after the initial neurological event. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11839-44. doi: 10.1073/pnas.0805065105. Epub 2008 Aug 8.

  PMID: 18689680 BACKGROUND

• Porichis F, Hart MG, Griesbeck M, Everett HL, Hassan M, Baxter AE, Lindqvist M, Miller SM, Soghoian DZ, Kavanagh DG, Reynolds S, Norris B, Mordecai SK, Nguyen Q, Lai C, Kaufmann DE. High-throughput detection of miRNAs and gene-specific mRNA at the single-cell level by flow cytometry. Nat Commun. 2014 Dec 4;5:5641. doi: 10.1038/ncomms6641.

  PMID: 25472703 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Cryopreserved peripheral blood mononuclear cells (PBMC)

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Motor Activity

Interventions

teriflunomide

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Behavior

Study Officials

• David Haegert, MD

  McGill University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 7, 2018
• First Posted: June 19, 2018
• Study Start: December 1, 2016
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: March 24, 2021

Record last verified: 2021-03

Locations

CA (1)