Effect of Teriflunomide on Immune Cell Subsets in the Blood of Patients With Multiple Sclerosis

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2012-005324-16-BE
• Date of registration: 17/04/2013
• Prospective Registration: Yes
• Primary sponsor: Genzyme Corporation
• Public title: Effect of Teriflunomide on Immune Cell Subsets in the Blood of Patients With Multiple Sclerosis
• Scientific 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 - TERI-DYNAMIC
• Date of first enrolment: 27/08/2013
• Target sample size: 68
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005324-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Main study period is followed by an extension period If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Reference population of untreated healthy subjects Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, Germany, Netherlands

Contacts

• Name: Brigitte De Witte
• Affiliation: Sanofi Belgium

• Name: Brigitte De Witte
• Affiliation: Sanofi Belgium

Key inclusion & exclusion 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 ß-1 or Glatiramer acetate and a period of at least 2 weeks without IFN ß-1 or Glatiramer acetate before switching to teriflunomide.
Male and female patients, between 18 and 56 years of age, exclusive.

Healthy volunteers (for Germany only):
- 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 68
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

multiple sclerosis
MedDRA version: 14.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Teriflunomide
Product Code: HMR1726
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TERIFLUNOMIDE
CAS Number: 108605-62-5
Current Sponsor code: HMR1726
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 14-

Primary Outcome(s)

Primary end point(s): Change from baseline in Lymphocyte subset parameters as
measured by flow cytometry

Secondary Objective: 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.

Timepoint(s) of evaluation of this end point: At 12 weeks and 24 weeks

Main 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 Outcome(s)

Secondary end point(s): 1) Change from baseline in biased T cell clonal repertoire based T
cell receptor (TCR) spectratyping
2) Change from baseline in serum cytokine as measured by
multicytokine array tool
3) Change from baseline in Mitogen/TCR-specific T cell proliferation
as measured by flow cytometry

Timepoint(s) of evaluation of this end point: At 12 weeks and 24 weeks

Secondary ID(s)

LPS13539

Source(s) of Monetary Support

Genzyme Corporation