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
- Conditions
- MSmultiple sclerosis10012303
- Registration Number
- NL-OMON40257
- Lead Sponsor
- Sanofi-aventis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
Patients:
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 *-1 or Glatiramer acetate and a period of at least 2 weeks without IFN *-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.
Patients:
- 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 *mol/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.
- Known history of hepatitis.
- 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.;Healthy volunteers:
- Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness.
- Blood donation, any volume, within 2 months before inclusion or according to local regulations).
- Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or asymptomatic postural hypotension defined as a decrease in systolic b
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Change from baseline in lymphocyte subset parameters as measured by flow<br /><br>cytometry. [Time frame for evaluation: At 12 weeks and 24 weeks]</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Change from baseline in biased T cell clonal repertoire based T cell receptor<br /><br>(TCR) spectratyping [Time frame for evaluation: At 12 weeks and 24 weeks]<br /><br>- Change from baseline in serum cytokine as measured by multicytokine array<br /><br>tool [Time frame for evaluation: At 12 weeks and 24 weeks]<br /><br>- Change from baseline in Mitogen/TCR-specific T cell proliferation as measured<br /><br>by flow cytometry [Time frame for evaluation: At 12 weeks and 24 weeks]</p><br>