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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01252355




Trial ID
NCT01252355
Ethics application status
Date submitted
30/11/2010
Date registered
2/12/2010
Date last updated
30/05/2014

Titles & IDs
Public title
Efficacy and Safety of Teriflunomide in Patients With Relapsing Multiple Sclerosis and Treated With Interferon-beta
Scientific title
A Multi-center Double-blind Parallel-group Placebo-controlled Study of the Efficacy and Safety of Teriflunomide in Patients With Relapsing Multiple Sclerosis Who Are Treated With Interferon-beta
Secondary ID [1] 0 0
2010-023172-12
Secondary ID [2] 0 0
EFC6058
Universal Trial Number (UTN)
Trial acronym
TERACLES
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Teriflunomide
Treatment: Drugs - Placebo (for teriflunomide)
Treatment: Drugs - Interferon-beta (IFN-beta)

Experimental: Teriflunomide 7 mg + IFN-beta - Teriflunomide 7 milligram (mg) once a day concomitantly with IFN-beta therapy.

Experimental: Teriflunomide 14 mg + IFN-beta - Teriflunomide 14 mg once a day concomitantly with IFN-beta therapy.

Placebo Comparator: Placebo + IFN-beta - Placebo (for teriflunomide) once a day concomitantly with IFN-beta therapy.


Treatment: Drugs: Teriflunomide
Film-coated tablet
Oral administration

Treatment: Drugs: Placebo (for teriflunomide)
Film-coated tablet
Oral administration

Treatment: Drugs: Interferon-beta (IFN-beta)
Any of the IFN-beta which are approved for marketed use in the country where the patient is enrolled.
Administration according to the package insert.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Relapse Rate (ARR) (Poisson Regression Estimates) - ARR is the total number of confirmed relapses that occurred during the treatment period divided by the total number of patient-years treated. Each episode of relapse (appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever) was to be confirmed by an increase in Expanded Disability Status Scale (EDSS) score or Functional System scores. To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group, region of enrollment and IFN-beta dose stratum, and number of relapses in the year prior to randomization as covariates).
Timepoint [1] 0 0
Up to a maximum of 108 weeks depending on time of enrollment
Secondary outcome [1] 0 0
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per Scan (Poisson Regression Estimates) - Number of Gd-enhancing T1-lesions per scan is the total number of Gd-enhancing T1-lesions that occurred during the treatment period divided by the total number of scans performed during the treatment period. To account for the different number of scans among participants, a Poisson regression model with robust error variance was used (total number of Gd-enhancing T1-lesions as response variable; log-transformed number of scans as offset variable; treatment group, region of enrollment, IFN-beta dose stratum and baseline number of Gd-enhancing T1-lesions as covariates).
Timepoint [1] 0 0
Up to a maximum of 108 weeks depending on time of enrollment
Secondary outcome [2] 0 0
Time to 12-Week Sustained Disability Progression - The 12-week sustained disability progression was defined as an increase from baseline of at least 1-point in EDSS score (at least 0.5-point for participants with baseline EDSS score >5.5) that persisted for at least 12 weeks. Probability of disability progression was to be estimated using Kaplan-Meier method.
Timepoint [2] 0 0
Up to a maximum of 108 weeks depending on time of enrollment
Secondary outcome [3] 0 0
Brain MRI Assessment: Volume of Gd-enhancing T1-lesions Per MRI Scan - Total volume of Gd-enhancing T1-lesions per scan is the sum of the volumes of Gd-enhancing T1-lesions observed during the treatment period divided by the total number of scans performed during the treatment period.
Timepoint [3] 0 0
Up to a maximum of 108 weeks depending on time of enrollment
Secondary outcome [4] 0 0
Brain MRI Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) at Week 24 - The total lesion volume (burden of disease) is the total volumes of hyperintense on T2 plus hypointense on T1 as measured by MRI scan. Least-square means were estimated using a Mixed-effect model with repeated measures (MMRM) on cubic root transformed volume data with factors for treatment, region, IFN-beta dose stratum, visit, treatment-by-visit interaction, cubic root transformed baseline burden of disease, and baseline-by-visit interaction.
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
Time to Relapse: Kaplan-Meier Estimates of the Probability of no Relapse at Week 24, 48, and 72 - Probability of no relapse at 24, 48 and 72 weeks was estimated using Kaplan-Meier method on the time to relapse defined as the time from randomization to first EDSS confirmed relapse. Participants free of confirmed relapse (no EDSS confirmed relapse observed on treatment) were censored at the date of the last study drug intake. Kaplan-Meier method consists in computing probabilities of non-occurrence of event at any observed time of event and multiplying successive probabilities for time <=t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t.
Timepoint [5] 0 0
Up to a maximum of 108 weeks depending on time of enrollment
Secondary outcome [6] 0 0
Change From Baseline in Fatigue Impact Scale (FIS) Total Score at Week 24 - FIS is a participant-reported scale that qualifies the impact of fatigue on daily life in participants with MS.
Timepoint [6] 0 0
Baseline, Week 24
Secondary outcome [7] 0 0
Change From Baseline in Short Form Generic Health Survey - 36 Items, Version 2 (SF-36v2) Summary Scores at Week 24 - SF-36 scale is a generic, self-administered, health-related quality-of-life (QOL) instrument.
Timepoint [7] 0 0
Baseline, Week 24
Secondary outcome [8] 0 0
Resource Utilization When Relapse - Resource utilization each time a participant experiences an MS relapse, specifically the number of hospitalizations, the number of over night spent in the hospital and number of intensive care admissions if hospitalized were to be reported.
Timepoint [8] 0 0
Up to a maximum of 108 weeks depending on time of enrollment
Secondary outcome [9] 0 0
Overview of Adverse Events (AEs) - AEs are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
Timepoint [9] 0 0
First study drug intake up to 28 days after last study drug intake, for up to 112 weeks

Eligibility
Key inclusion criteria
Inclusion criteria :

- Patient with relapsing forms of MS treated with IFN-beta

- Stable dose of IFN-beta (approved brand) for at least 6 months prior to randomization

- Disease activity in the 12 months prior to randomization and after first 3 months of
IFN-beta treatment (defined by at least 1 relapse supported by EDSS or equivalent
neurological examination, or, at least 1 brain or spinal cord MRI with at least one T1
gadolinium enhancing lesion)
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

- McDonald criteria for MS diagnosis not met at time of screening visit

- EDSS score greater than (>) 5.5 at randomization visit

- A relapse within 30 days prior randomization

- Persistent significant or severe infection

- Patients must not have used adrenocorticotrophic hormone or systemic corticosteroids
for 2 weeks prior to randomization

- Prior or concomitant use of cytokine therapy (except baseline interferons), glatiramer
acetate or intravenous immunoglobulins in the 3 months preceding randomization

- Liver function impairment or persisting elevations (confirmed by retest) of alanine
aminotransferase (ALT), aspartate aminotransferase (AST), or direct bilirubin greater
than 2 times the upper limit of normal range (ULN)

- Active hepatitis or hepatobiliary disease or known history of severe hepatitis

- Pregnant or breast-feeding women or those who were planning to become pregnant during
the study

- Significantly impaired bone marrow function or significant anemia, leukopenia, or
thrombocytopenia

- Human Immunodeficiency Virus (HIV) positive

- Known history of active tuberculosis not adequately treated

- Prior use within 2 years preceding randomization or concomitant use of cladribine and
mitoxantrone

- Prior use within 6 months preceding randomization or concomitant use of natalizumab,
or any other immunosuppressive agents such as azathioprine, cyclophosphamide,
cyclosporine, methotrexate, mycophenolate, or fingolimod

The above information is not intended to contain all considerations relevant to a patient'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 assessing the outcomes
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
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Investigational Site Number 036008 - Bedford Park
Recruitment hospital [2] 0 0
Investigational Site Number 036005 - Chatswood
Recruitment hospital [3] 0 0
Investigational Site Number 036001 - Heidelberg West
Recruitment hospital [4] 0 0
Investigational Site Number 036004 - Kogarah
Recruitment hospital [5] 0 0
Investigational Site Number 036010 - New Lambton
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
2067 - Chatswood
Recruitment postcode(s) [3] 0 0
3081 - Heidelberg West
Recruitment postcode(s) [4] 0 0
2217 - Kogarah
Recruitment postcode(s) [5] 0 0
2305 - New Lambton
Recruitment outside Australia
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Salford

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, in comparison to
placebo, on frequency of Multiple Sclerosis (MS) relapses in patients with relapsing forms of
MS who are treated with Interferon-beta (IFN-beta).

The secondary objectives were:

- Assess the effect of teriflunomide, in comparison to placebo, when added to IFN-beta on:

- Disease activity as measured by brain Magnetic Resonance Imaging (MRI)

- Disability progression

- Burden of disease and disease progression as measured by brain MRI

- Evaluate the safety and tolerability of teriflunomide when added to IFN-beta therapy

- Assess the pharmacokinetics of teriflunomide in use in addition to baseline IFN-beta
therapy

- Assess associations between variations in genes and clinical outcomes (safety and
efficacy)

- Assess other measures of efficacy of teriflunomide such as fatigue and health-related
quality of life

- Assess measures of health economics (hospitalization due to relapse, including the
length of stay and any admission to intensive care unit)
Trial website
https://clinicaltrials.gov/show/NCT01252355
Trial related presentations / publications
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