A randomized, double-blind, placebo-controlled, parallel group design study to evaluate the efficacy and safety of teriflunomide (HMR1726D) in reducing the frequency of relapses and delaying the accumulation of physical disability in subjects with multiple sclerosis with relapses

• Register: EUCTR
• Last refreshed on: 14 March 2016
• Main ID: EUCTR2004-000555-42-AT
• Date of registration: 28/10/2004
• Prospective Registration: Yes
• Primary sponsor: Sanofi-Aventis US, Inc.
• Public title: A randomized, double-blind, placebo-controlled, parallel group design study to evaluate the efficacy and safety of teriflunomide (HMR1726D) in reducing the frequency of relapses and delaying the accumulation of physical disability in subjects with multiple sclerosis with relapses
• Scientific title: A randomized, double-blind, placebo-controlled, parallel group design study to evaluate the efficacy and safety of teriflunomide (HMR1726D) in reducing the frequency of relapses and delaying the accumulation of physical disability in subjects with multiple sclerosis with relapses
• Date of first enrolment: 02/12/2004
• Target sample size: 1080
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-000555-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Czech Republic, Denmark, Estonia, Italy, Norway, Portugal, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects meeting all of the following criteria will be considered for enrollment into the study:
- MS subjects, aged 18 to 55, who are ambulatory (EDSS less or equal than 5.5)
- Exhibiting a relapsing clinical course, with or without progression (Relapsing Remitting, Secondary Progressive or Progressive Relapsing)
- Meeting McDonald’s criteria for MS diagnosis
- Experienced at least 1 relapse over the 1 year preceding the trial or at least 2 relapses over the 2 years preceding the trial
- No relapse onset in the preceding 60 days prior to randomization
- During the 4 weeks prior to randomization, subjects must have been clinically stable, without adrenocorticotrophic hormone (ACTH) or systemic steroid treatment
- Signed main informed consent form and the informed consent for HIV testing
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Subjects with significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia
- Subjects 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 subject who has received lymphoid irradiation
- Human immunodeficiency virus (HIV) positive status; known history of active tuberculosis not adequately treated; persistent significant or severe infection
- Pregnancy, breastfeeding, subjects wishing to parent children during the course of the trial
- Therapies that are disallowed (minimum of 4 weeks prior to randomization): phenytoin, warfarin, tolbutamide, St. John's Wort or cholestyramine
- Subjects must not have used ACTH or systemic corticosteroids for 4 weeks prior to randomization
- Prior or concomitant use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin or methotrexate;
- Prior use of natalizumab (Tysabri)
- Prior use of interferons or cytokine therapy in the preceding 4 months; prior use of glatiramer acetate therapy in the preceding 6 months; prior use of intravenous immunoglobulins in the preceding 6 months; prior use of any investigational drug in the preceding 6 months; previous treatment with teriflunomide or leflunomide (ARAVA®)
- Contraindication for MRI, i.e., presence of pacemaker, metallic implants in high-risk areas (i.e., artificial heart valves, aneurysm/vessel clips), presence of metallic material (i.e., shrapnel) in high risk areas, known history of allergy to any contrast medium, or history of claustrophobia that would prevent completion of all protocol-scheduled MRI. Hip implants are not contraindicated.
- Liver function impairment or persisting elevations of SGPT/ALT, serum glutamic oxaloacetic transaminase (SGOT/AST), or direct bilirubin greater than 1.5-fold the upper limit of normal (ULN);
- Persisting elevations of serum amylase or lipase greater than 2-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
- Known history of chronic pancreatic disease or pancreatitis
- Moderate to severe impairment of renal function, as shown by serum creatinine >133 µmol/L (or >1.5 mg/dL)
- Likelihood of requiring treatment during the study period with drugs not permitted by the clinical study protocol
- Clinically relevant cardiovascular, hepatic, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the subject at risk by participating in the study
- History of drug or alcohol abuse
- Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study
- Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol


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

Health Condition(s) or Problem(s) studied

Multiple sclerosis
MedDRA version: 12.0 Level: PT Classification code 10028245 Term: Multiple sclerosis

Intervention(s)

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: 7-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

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-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary efficacy variable will be the annual relapse rate, defined as the number of relapses per subject-year. A gross estimate of annual relapse rate for a treatment group would be the total number of relapses incurred by the subjects in that group divided by the sum of study durations (in year) of all subjects in the group.

Secondary Objective: To Evaluate
- the effect of teriflunomide on delaying the accumulation of disability AT 2 YEARS as assessed by the Kurtzke EDSS
- the effects of teriflunomide on MRI variables, burden of disease (volume of abnormal brain tissue on MRI) and other MRI variables including number and volume of gadolinium-enhanced T1 lesions, volume of T2 lesion, volume of T1 hypointense lesions, atrophy and a composite.
- the effect of teriflunomide on subject-reported fatigue as assessed by the Fatigue Impact Scale (FIS)
- the safety and tolerability of teriflunomide by means of adverse event reports, physical examinations, vital signs, and laboratory evaluations

Main Objective: To determine the effect of teriflunomide in reducing the frequency of relapses in subjects with relapsing multiple sclerosis.

Secondary ID(s)

EFC6049

2004-000555-42-NO