A randomized, multinational, double-blind, placebo-controlled, parallel-group design pilot study to estimate the tolerability, safety, pharmacokinetics, and pharmacodynamic effects of teriflunomide for 24 weeks when added to treatment with glatiramer acetate in subjects with multiple sclerosis

• Register: EUCTR
• Last refreshed on: 28 January 2013
• Main ID: EUCTR2006-004893-29-DE
• Date of registration: 06/02/2007
• Prospective Registration: Yes
• Primary sponsor: Sanofi-aventis U.S. Inc.
• Public title: A randomized, multinational, double-blind, placebo-controlled, parallel-group design pilot study to estimate the tolerability, safety, pharmacokinetics, and pharmacodynamic effects of teriflunomide for 24 weeks when added to treatment with glatiramer acetate in subjects with multiple sclerosis
• Scientific title: A randomized, multinational, double-blind, placebo-controlled, parallel-group design pilot study to estimate the tolerability, safety, pharmacokinetics, and pharmacodynamic effects of teriflunomide for 24 weeks when added to treatment with glatiramer acetate in subjects with multiple sclerosis
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-004893-29
• 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, Germany, Italy, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
- Patients of both gender aged 18 to 55 years with a diagnosis of multiple sclerosis (as defined by McDonald's criteria) who are ambulatory (Expanded Disability Status Scale [EDSS] of < or = to 5.5).
-Stable dose of glatiramer acetate for at least 26 weeks prior to the screening visit
-No onset of MS relapse in the preceding 60 days prior to randomization
-Clinically stable for 4 weeks prior to randomization
-Main informed consent and informed consent for HIV testing forms signed
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:
*disease related:
-cancer, lymphoproliferative disease or lymphoïd irradiation
-Impaired bone marrow function; significant anemia, leukopenia, or thrombocytopenia
-Congenital or acquired severe immunodeficiency, HIV positive subjects, persistent significant or severe infection, tuberculosis
-Liver function impairment or persisting elevation of alanine transaminase(ALT) aspartate transferase (AST), or direct bilirubine >1.5 fold the upper limit of normal (ULN)
- Persisting elevations of serum amylase or lipase greater to 2-fold the upper limit of normal
-chronic pancreatic disease or pancreatitis, chronic active hepatitis
-Hypoprotéinemia
-Moderate to severe impairment of renal function
-Clinically relevant cardiovascular, hypertensive, hepatic, neurological, endocrine, or other systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the subject at risk by participing in the study
*Prior or concomitant use or likelihood of requiring treatment during the study period with drugs not permitted
- cladribine, mitoxantrone, azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate.
- St.John's Wort, phenytoin, warfarin, tolbutamide or cholestyramine; adrenocorticotropic hormone (ACTH) or systemic corticosteroids within 4 weeks prior to randomization (minimum 4 weeks before randomization)
-natalizumab TYSABRI
-Interferon-beta or cytokine therapy, immunoglobins or any investigational drug in the preceding 24 weeks
- Previous treatment with teriflunomide or leflunomide (ARAVA)
*Contra-indicating for MRI
*Other
-Pregnancy, breastfeeding, wishing to parent children
-History of drug or alcohol abuse
-Mental condition rendering the subject unable to understand the nature, scope, and possible consequence of the study
-Subject unlikely to comply with protocol
-Subject involved in the conduct of protocol


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

Health Condition(s) or Problem(s) studied

Multiple sclerosis

Intervention(s)

Product Name: teriflunomide
Product Code: HMR1726D
Pharmaceutical Form: Tablet
INN or Proposed INN: teriflunomide
CAS Number: 108605-62-5
Current Sponsor code: HMR1726D
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 7-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: teriflunomide
Product Code: HMR1726D
Pharmaceutical Form: Tablet
INN or Proposed INN: teriflunomide
CAS Number: 108605-62-5
Current Sponsor code: HMR1726D
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 14-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: *Effects of teriflunomide 7 and 14 mg, compared with placebo, in combination with a stable dose of glatiramer acetate on :
- total number of gadolinium enhancing lesions per T1-weighted MRI scan over the study period
- burden of disease ( defined as total volume of all lesions as measured by T2-weighted MRI scans)
- relapse rate (defined as number of annualized relapses per year) and the proportion of subjects who experience objective relapses during the study
- subject reported fatigue as measured by the Fatigue Impact Scale (FIS)
*Population pharmacokinetic analyses of teriflunomide following 7 mg and 14 mg doses, in combination with a stable dose of glatiramer acetate.

Primary end point(s): Safety (adverse event reports; physical examination and laboratory evaluation)

Main Objective: To investigate the tolerability and safety of a 7 mg and a 14 mg dose of teriflunomide administered once daily for 24 weeks, compared with placebo in subjects with multiple sclerosis who are concurrently on a stable dose of glatiramer acetate.

Secondary ID(s)

2006-004893-29-GB

PDY6046