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 (TERICIS)

A National, Multi-center 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

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).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Teriflunomide

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Besançon, France, 25030
    • CHU de Besancon
  • Lille, France, 59037
    • CHU de Lille
  • Montpellier, France, 34295
    • CHU de Montpellier
  • Nice, France, 06000
    • CHU de Nice
  • Strasbourg, France, 67098
    • CHU de Strasbourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Teriflunomide; Teriflunomide 14 mg Once Daily	Drug: Teriflunomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event reporting	evaluation of safety and tolerability of teriflunomide 14mg per day	throughout study completion an average of 6 months
Adverse Events That Are Related to Treatment		throughout study completion an average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conversion based on MRI	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	throughout study completion an average of 6 months
Conversion based on Clinical evaluation	Conversion to clinically definite MS based on clinical evaluation and annualized relapse rate (ARR), defined as number of relapses per patient-year	throughout study completion an average of 6 months
Conversion based on annualized relapse rate (ARR)	Conversion to clinically definite MS based on clinical evaluation and annualized relapse rate (ARR), defined as number of relapses per patient-year	throughout study completion an average of 6 months
volume of abnormal brain tissue on MRI		3 years
Disability progression defined as a 1.0-point increase in EDSS score	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	confirmed after at least 12 weeks
Proportion of disability-free subjects as assessed by the EDSS	Proportion of disability-free subjects as assessed by the EDSS	throughout study completion an average of 1 year
Fatigue Impact Scale	Patient-reported fatigue based on the Fatigue Impact Scale	throughout study completion an average of 1 year
Quality of life using SF-36		throughout study completion an average of 1 year

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2015
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: September 22, 2015
• First Submitted That Met QC Criteria: October 23, 2015
• First Posted (Estimate): October 27, 2015

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Teriflunomide
• Other Study ID Numbers: 15-PP-06