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A Study to Evaluate the Safety of Long Term Treatment With Teriflunomide 14 mg Once Daily in Patients With a First Clinical Episode Suggestive of Multiple Sclerosis in a Long-term Extension Period

Phase 3
Completed
Conditions
Multiple Sclerosis
Interventions
Registration Number
NCT02587195
Lead Sponsor
Centre Hospitalier Universitaire de Nice
Brief Summary

National, multicenter study:

The study consists of 3 periods:

1. A baseline visit to confirm that patient is still in CIS status. All patients will be clinically evaluated for CDMS and an MRI (less than 2 months) will be analyzed to exclude MS patients according to 2010 Mc Donald's criteria.

2. Treatment period with timed evaluations

3. Post-treatment period: 4 weeks, with 2 visits following study drug discontinuation and accelerated elimination procedure. All patients who discontinue the study drug and according to investgator's decision, will perform the accelerated elimination procedure and the post- accelerated elimination visits (at 2 and 4 weeks after the end of treatment (EOT).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
5
Inclusion Criteria
  • Patients enrolled in TOPIC study and extension of TOPIC study and currently treated in French extension of TOPIC study who did not convert into MS.
  • A baseline MRI scan (performed less than 2 months before baseline Visit ) confirming that patient is still in CIS status.
Exclusion Criteria
  • Contraindication for MRI,
  • Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major systemic disease or procedure/medication 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
  • Known history of active tuberculosis not adequately treated
  • Persistent significant or severe infection
  • History of drug or alcohol abuse
  • Patients must not have used Adrenocorticotrophic hormone (ACTH) or systemic corticosteroids for 2 weeks prior to inclusion
  • Prior use within 4 weeks before inclusion or concomitant use of cholestyramine
  • Prior or concomitant use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate
  • Prior or concomitant use of interferons, cytokine therapy, glatiramer acetate or intravenous immunoglobulins
  • Prior or concomitant use of natalizumab (Tysabri®)
  • Pregnant or breast-feeding women
  • Women of childbearing potential not protected by effective contraceptive method of birth control and/or who are unwilling or unable to be tested for pregnancy.
  • Women wishing to become pregnant during the course of the trial
  • Patients with significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia
  • Human immunodeficiency virus (HIV) positive patient
  • 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
  • Liver function impairment or persisting elevations (confirmed by retest) of serum glutamic pyruvic transaminase (SGPT/ALT), serum glutamic oxaloacetic transaminase (SGOT/AST), or direct bilirubin greater than 1.5-fold the upper limit of normal
  • Known history of active hepatitis
  • Hypoproteinemia (e.g., 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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TeriflunomideTeriflunomideTeriflunomide 14 mg Once Daily
Primary Outcome Measures
NameTimeMethod
Adverse event reportingthroughout study completion an average of 6 months

evaluation of safety and tolerability of teriflunomide 14mg per day

Adverse Events That Are Related to Treatmentthroughout study completion an average of 6 months
Secondary Outcome Measures
NameTimeMethod
Conversion based on MRIthroughout study completion an average of 6 months

Conversion to definite MS based on MRI data as defined by the demonstration of dissemination of MRI lesions in time (based on the 2010 revised McDonald criteria) within 3 years

Disability progression defined as a 1.0-point increase in EDSS scoreconfirmed after at least 12 weeks

to disability progression (12 weeks), defined as a 1.0-point increase in EDSS score (or 0.5-point increase for baseline EDSS \>5.5) confirmed after at least 12 weeks

Fatigue Impact Scalethroughout study completion an average of 1 year

Patient-reported fatigue based on the Fatigue Impact Scale

Quality of life using SF-36throughout study completion an average of 1 year
Conversion based on Clinical evaluationthroughout study completion an average of 6 months

Conversion to clinically definite MS based on clinical evaluation and annualized relapse rate (ARR), defined as number of relapses per patient-year

volume of abnormal brain tissue on MRI3 years
Conversion based on annualized relapse rate (ARR)throughout study completion an average of 6 months

Conversion to clinically definite MS based on clinical evaluation and annualized relapse rate (ARR), defined as number of relapses per patient-year

Proportion of disability-free subjects as assessed by the EDSSthroughout study completion an average of 1 year

Proportion of disability-free subjects as assessed by the EDSS

Trial Locations

Locations (5)

CHU de Lille

🇫🇷

Lille, France

CHU de Nice

🇫🇷

Nice, France

CHU de Montpellier

🇫🇷

Montpellier, France

CHU de Besançon

🇫🇷

Besançon, France

CHU de Strasbourg

🇫🇷

Strasbourg, France

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