Effect of Teriflunomide on Immune Cell Subsets in the Blood of Patients With Multiple Sclerosis (TERI-DYNAMIC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Sanofi
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01863888
First received: May 23, 2013
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

Primary Objective:

To measure the effect of Teriflunomide on lymphocytes subsets in patients with relapsing forms of multiple sclerosis as compared with baseline values and those of a reference population of untreated healthy subjects.

Secondary Objectives:

To assess if Teriflunomide treatment results in biased T cell clonal diversity. To assess the effect of Teriflunomide on the function of peripheral blood mononuclear cells (proliferation and cytokine production in situ).

To assess the circulating cytokines profile in the serum of Relapsing Multiple Sclerosis (RMS) patients during a 24-week treatment versus baseline and healthy controls.

To assess the reversibility of all parameter changes in patients who discontinue treatment after accelerated elimination procedure with cholestyramine or activated charcoal.


Condition Intervention Phase
Multiple Sclerosis
Drug: teriflunomide HMR1726
Drug: cholestyramine
Drug: charcoal
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Exploratory Open Label Study to Investigate the Effect of Teriflunomide on Immune Cell Subsets in the Blood of Patients With Relapsing Forms of Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Change from baseline in Lymphocyte subset parameters as measured by flow cytometry [ Time Frame: At 12 weeks and 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in biased T cell clonal repertoire based T cell receptor (TCR) spectratyping [ Time Frame: At 12 weeks and 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in serum cytokine as measured by multicytokine array tool [ Time Frame: At 12 weeks and 24 weeks ] [ Designated as safety issue: No ]
  • Change from baseline in Mitogen/TCR-specific T cell proliferation as measured by flow cytometry [ Time Frame: At 12 weeks and 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 68
Study Start Date: September 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: teriflunomide (HMR1726)
Participants administered 14mg Teriflunomide once daily, oral. For participants who permanently discontinue Teriflunomide, an accelerated elimination procedure with either cholestyramine or charcoal will be administered.
Drug: teriflunomide HMR1726
Pharmaceutical form:tablet Route of administration: oral
Drug: cholestyramine
Pharmaceutical form:powder Route of administration: oral
Drug: charcoal
Pharmaceutical form:granule Route of administration: oral
No Intervention: Reference population
Untreated healthy subjects

Detailed Description:

The duration of the study for patients is 32 weeks which includes 4 weeks for screening, 24 weeks for treatment and 4 weeks for follow-up. An extension of the study is proposed until Teriflunomide is commercially available in the country where patient lives.

The duration of the study for healthy volunteers is 25 weeks which includes only one week for screening.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

Patients (male and female) with relapsing forms of multiple sclerosis meeting McDonald criteria for MS at the screening visit and having either one of the following treatment status:

  • Naïve to disease modifying (DM) treatment or no DM treatment for more than 2 years
  • Or currently (not more than 3 months interruption) on MS therapy with IFN β-1 or Glatiramer acetate and a period of at least 2 weeks without IFN β-1 or Glatiramer acetate before switching to teriflunomide.

Male and female patients, between 18 and 56 years of age, exclusive.

Healthy volunteers:

Male and female subjects, between 18 and 56 years of age, exclusive. Body weight between 50.0 and 95.0 kg, inclusive, if male; and between 40.0 and 85.0 kg, inclusive, if female, body mass index between 18.0 and 30.0 kg/m2, inclusive.

Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).

Normal vital signs after 10 minutes resting in supine position:

  • 95 mmHg < systolic blood pressure (SBP) <140 mmHg
  • 45 mmHg < diastolic blood pressure (DBP) <90 mmHg
  • 40 bpm < heart rate (HR) <100 bpm Normal standard 12-lead electrocardiogram (ECG) after 10 minutes resting in supine position; 120 ms < PR <220 ms, QRS <120 ms, QTc ≤ 430 ms if male, ≤ 450 ms if female.

Laboratory parameters within the normal range (or defined screening threshold for the Investigator site), unless the Investigator considers an abnormality to be clinically irrelevant for healthy subjects; however liver function parameter(s) should not exceed the upper laboratory norm.

Exclusion criteria:

Did not consent to HIV testing (the specifics of informed consent process for the HIV testing should be done in accordance with local guidelines).

A relapse within 30 days prior to screening. Clinically relevant cardiovascular, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the patient at risk by participating in the study.

Patients with a congenital or acquired severe immunodeficiency, a history of cancer (except for basal or squamous cell skin lesions which have been surgically excised, with no evidence of metastasis), lymphoproliferative disease, or any patient who has received lymphoid irradiation.

Human immunodeficiency virus (HIV) positive patients. Known history of active tuberculosis not adequately treated or positive QuantiFERON TB Gold test.

Hypoproteinemia (eg, in case of severe liver disease or nephrotic syndrome) with serum albumin <3.0 g/dL.

Moderate to severe impairment of renal function, as shown by serum creatinine >133 μmol/L (or >1.5 mg/dL).

Patients with significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia.

Acute or chronic infection. Liver function impairment or persisting elevations >1.5ULN (confirmed by retest) of serum glutamic pyruvic transaminase/ alanine aminotransferase (SGPT/ALT), serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST), or direct bilirubin greater than 1.5-fold the upper limit of normal.

Use of adrenocorticotrophic hormone (ACTH) or systemic corticosteroids for 2 weeks prior to screening.

Prior or concomitant use of cytokine therapy or intravenous immunoglobulins in the 3 months prior to screening.

Prior use of alemtuzumab or cladribine. Prior use (within 1 year) of fingolimod (Gylenia®). Prior use (within 2 years) of mitoxantrone, natalizumab (Tysabri®), or immunosuppressant agents (i.e. azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate).

Prior treatment with teriflunomide, and prior or concomitant use of leflunomide (ARAVA®) or hypersensitivity to any of the other ingredients or excipients of the investigational product.

Prior use of any investigational drug in the 6 months preceding screening. Pregnant or breast-feeding women. Women of childbearing potential not utilizing effective contraceptive method and /or women of childbearing potential who are unwilling to or unable to be tested for pregnancy.

Known history of hypersensitivity to teriflunomide or leflunomide. Persisting elevations (confirmed by retest) of serum amylase or lipase greater than 2-fold the upper limit of normal.

Known history of chronic pancreatic disease or pancreatitis.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01863888

Contacts
Contact: For site information, send an email with site number to Contact-Us@sanofi.com

Locations
Belgium
Investigational Site Number 056001 Recruiting
Brussels, Belgium, 1070
Investigational Site Number 056002 Recruiting
Overpelt, Belgium, 3900
Investigational Site Number 056003 Recruiting
Sijsele-Damme, Belgium, 8340
Germany
Investigational Site Number 276-003 Active, not recruiting
Bad Mergentheim, Germany, 97980
Investigational Site Number 276-004 Recruiting
Hannover, Germany, 30625
Investigational Site Number 276-005 Recruiting
Marburg, Germany, 35043
Investigational Site Number 276-007 Recruiting
Mönchengladbach, Germany, 41061
Investigational Site Number 276-001 Recruiting
Münster, Germany, 48149
Investigational Site Number 276-002 Active, not recruiting
Ulm, Germany, 89073
Netherlands
Investigational Site Number 528001 Active, not recruiting
Sittard-Geleen, Netherlands, 6162BG
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01863888     History of Changes
Other Study ID Numbers: LPS13539, U1111-1139-8802
Study First Received: May 23, 2013
Last Updated: June 6, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes
Charcoal
Cholestyramine Resin
Antidotes
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014