Effect of Teriflunomide on Immune Cell Subsets in the Blood of Patients With Multiple Sclerosis
Information source: Sanofi
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Multiple Sclerosis
Intervention: teriflunomide HMR1726 (Drug); cholestyramine (Drug); charcoal (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Sanofi Official(s) and/or principal investigator(s): Clinical Sciences & Operations, Study Director, Affiliation: Sanofi
Summary
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.
Clinical Details
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
Study design: Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Change from baseline in Lymphocyte subset parameters as measured by flow cytometry
Secondary outcome: Change from baseline in biased T cell clonal repertoire based T cell receptor (TCR) spectratypingChange from baseline in serum cytokine as measured by multicytokine array tool Change from baseline in Mitogen/TCR-specific T cell proliferation as measured by flow cytometry
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
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
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.
Locations and Contacts
Investigational Site Number 056001, Brussels 1070, Belgium
Investigational Site Number 056002, Overpelt 3900, Belgium
Investigational Site Number 056003, Sijsele-Damme 8340, Belgium
Investigational Site Number 276-003, Bad Mergentheim 97980, Germany
Investigational Site Number 276-004, Hannover 30625, Germany
Investigational Site Number 276-005, Marburg 35043, Germany
Investigational Site Number 276-007, Mönchengladbach 41061, Germany
Investigational Site Number 276-001, Münster 48149, Germany
Investigational Site Number 276-002, Ulm 89073, Germany
Investigational Site Number 528001, Sittard-Geleen 6162BG, Netherlands
Additional Information
Starting date: October 2013
Last updated: March 12, 2015
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