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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00622700




Registration number
NCT00622700
Ethics application status
Date submitted
14/02/2008
Date registered
25/02/2008
Date last updated
13/03/2017

Titles & IDs
Public title
Phase III Study With Teriflunomide Versus Placebo in Patients With First Clinical Symptom of Multiple Sclerosis
Scientific title
An International, Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Two Year Treatment With Teriflunomide 7 mg Once Daily and 14 mg Once Daily Versus Placebo in Patients With a First Clinical Episode Suggestive of Multiple Sclerosis Plus a Long Term Extension Period
Secondary ID [1] 0 0
HMR1726D-3005
Secondary ID [2] 0 0
EFC6260
Universal Trial Number (UTN)
Trial acronym
TOPIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Teriflunomide
Treatment: Drugs - Placebo

Placebo comparator: Placebo/Teriflunomide 7 mg or Teriflunomide 14 mg - Core treatment period: Placebo matched to teriflunomide tablet once daily orally.

Extension treatment period: Re-randomized in 1:1 ratio to either teriflunomide 7 mg or 14 mg once daily orally.

Experimental: Teriflunomide 7 mg/7 mg - Core treatment period: Teriflunomide 7 mg tablet once daily orally.

Extension treatment period: Teriflunomide 7 mg tablet once daily orally.

Experimental: Teriflunomide 14 mg/14 mg - Core treatment period: Teriflunomide 14 mg tablet once daily orally.

Extension treatment period: Teriflunomide 14 mg tablet once daily orally.


Treatment: Drugs: Teriflunomide
Film-coated tablet Oral administration

Treatment: Drugs: Placebo
Film-coated tablet Oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Core Treatment Period: Time to Conversion to Clinically De?nite Multiple Sclerosis (CDMS)
Timepoint [1] 0 0
Up to a maximum of 108 weeks depending on time of enrollment
Secondary outcome [1] 0 0
Core Treatment Period: Time to Conversion to Definite Multiple Sclerosis (DMS)
Timepoint [1] 0 0
Up to a maximum of 108 weeks depending on time of enrollment
Secondary outcome [2] 0 0
Core Treatment Period: Annualized Relapse Rate (ARR)
Timepoint [2] 0 0
Up to a maximum of 108 weeks depending on time of enrollment
Secondary outcome [3] 0 0
Core Treatment Period: Brain Magnetic Resonance Imaging (MRI) Assessment: Change From Baseline in Total Lesion Volume at Week 108
Timepoint [3] 0 0
Baseline, Week 108
Secondary outcome [4] 0 0
Core Treatment Period: Brain MRI Assessment: Number of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per MRI Scan (Poisson Regression Estimates)
Timepoint [4] 0 0
Up to a maximum of 108 weeks depending on time of enrollment
Secondary outcome [5] 0 0
Core Treatment Period: Brain MRI Assessment: Volume of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per MRI Scan
Timepoint [5] 0 0
Up to a maximum of 108 weeks depending on time of enrollment
Secondary outcome [6] 0 0
Core Treatment Period: Brain MRI Assessment: Change From Baseline in Volume of Hypointense Post-Gadolinium T1 Lesion Component
Timepoint [6] 0 0
Baseline, Week 108
Secondary outcome [7] 0 0
Core Treatment Period: Brain MRI Assessment: Change From Baseline in Volume of T2 Lesion Component
Timepoint [7] 0 0
Baseline, Week 108
Secondary outcome [8] 0 0
Core Treatment Period: Brain MRI Assessment: Percent Change From Baseline in Atrophy
Timepoint [8] 0 0
Baseline, Week 108
Secondary outcome [9] 0 0
Core Treatment Period: Time to 12-Week Sustained Disability Progression
Timepoint [9] 0 0
Up to a maximum of 108 weeks depending on time of enrollment
Secondary outcome [10] 0 0
Core Treatment Period: Change From Baseline in EDSS at Week 108
Timepoint [10] 0 0
Baseline, Week 108
Secondary outcome [11] 0 0
Core Treatment Period: Change From Baseline in Fatigue Impact Scale (FIS) Total Score at Week 108
Timepoint [11] 0 0
Baseline, Week 108
Secondary outcome [12] 0 0
Core Treatment Period: Overview of Adverse Events (AEs)
Timepoint [12] 0 0
From first study drug intake up to 112 days after last intake in the placebo-controlled period or up to first intake in the extension treatment period, whichever occurred first
Secondary outcome [13] 0 0
Extension Treatment Period: Time to Conversion to Clinically De?nite Multiple Sclerosis (CDMS)
Timepoint [13] 0 0
From randomization in the core period up to 390 Weeks (Extension treatment period [maximum exposure: 283 Weeks])
Secondary outcome [14] 0 0
Extension Treatment Period: Overview of Adverse Events (AEs)
Timepoint [14] 0 0
From re-randomization up to 283 Weeks

Eligibility
Key inclusion criteria
* First acute or subacute, well-defined neurological event consistent with demyelination (that is, optic neuritis confirmed by an ophthalmologist, spinal cord syndrome, brainstem/cerebellar syndromes)
* Onset of MS symptoms occurring within 90 days of randomization
* A screening MRI scan with 2 or more T2 lesions at least 3 millimeter (mm) in diameter that are characteristic of MS
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Clinically relevant cardiovascular, hepatic, neurological, endocrine or other major systemic disease
* Significantly impaired bone marrow function
* Pregnancy or nursing
* Alcohol or drug abuse
* Use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate before enrollment
* Any known condition or circumstance that would prevent in the investigator's opinion compliance or completion of the study

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2016
Sample size
Target
Accrual to date
Final
618
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 1405 - Geelong
Recruitment hospital [2] 0 0
Investigational Site Number 1404 - Heidelberg
Recruitment hospital [3] 0 0
Investigational Site Number 1407 - Hobart
Recruitment hospital [4] 0 0
Investigational Site Number 1401 - Parkville
Recruitment postcode(s) [1] 0 0
3220 - Geelong
Recruitment postcode(s) [2] 0 0
3081 - Heidelberg
Recruitment postcode(s) [3] 0 0
7001 - Hobart
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective was to demonstrate the effect of teriflunomide (HMR1726) (14 milligram per day \[mg/day\] and 7 mg/day), in comparison to placebo, for reducing conversion of participants presenting with their first clinical episode consistent with multiple sclerosis (MS) to clinically definite multiple sclerosis (CDMS).

The secondary objectives were:

* To demonstrate the effect of teriflunomide, in comparison to placebo, on:

* Reducing conversion to definite multiple sclerosis (DMS)
* Reducing annualized relapse rate (ARR)
* Reducing disease activity/progression as measured by Magnetic Resonance Imaging (MRI)
* Reducing accumulation of disability for at least 12 weeks as measured by the Expanded Disability Status Scale (EDSS)
* Proportion of disability-free participants as assessed by the EDSS
* Reducing participant-reported fatigue
* To evaluate the safety and tolerability of teriflunomide
* To evaluate the pharmacokinetics (PK) of teriflunomide
* Optional pharmacogenomic testing aimed at assessing the association between the main enzyme systems of teriflunomide metabolism and hepatic safety, and other potential associations between gene variations and clinical outcomes
Trial website
https://clinicaltrials.gov/study/NCT00622700
Trial related presentations / publications
Miller AE, Wolinsky JS, Kappos L, Comi G, Freedman MS, Olsson TP, Bauer D, Benamor M, Truffinet P, O'Connor PW; TOPIC Study Group. Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014 Oct;13(10):977-86. doi: 10.1016/S1474-4422(14)70191-7. Epub 2014 Sep 2.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00622700