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Efficacy, Safety and Pharmacokinetics of Teriflunomide in Pediatric Patients With Relapsing Forms of Multiple Sclerosis (TERIKIDS)

Primary Purpose

Multiple Sclerosis

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Teriflunomide
Placebo
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis

Eligibility Criteria

10 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

  • Participants with relapsing MS were eligible. Participants who met the criteria of MS based on McDonald criteria 2010 and International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric MS, version of 2012 and had:

    • at least one relapse (or attack) in the 12 months preceding screening or,
    • at least two relapses (or attack) in the 24 months preceding screening.
  • Less than 18 years of age and greater than or equal to (>=) 10 years of age at randomization. Specific for the Russian Federation from 18 December 2014 to 26 July 2016, less than or equal to 17 years of age and >= 13 years of age at randomization.
  • Signed informed consent/assent obtained from participant and participant's legal representative (parents or guardians) according to local regulations.

Exclusion criteria:

  • Expanded disability status scale score greater than 5.5 at screening or randomization visits.
  • Relapse within 30 days prior to randomization.

  • Treated with:

    • glatiramer acetate, interferons, or dimethyl fumarate within 1 month prior to randomization.
    • fingolimod, or intravenous immunoglobulins within 3 months prior to randomization.
    • natalizumab, other immunosuppressant or immunomodulatory agents such as cyclophosphamide, azathioprine, cyclosporine, methotrexate, mycophenolate, within 6 months prior to randomization.
    • cladribine or mitoxantrone within 2 years prior to randomization.
  • Treated with alemtuzumab at any time.
  • History of human immunodeficiency virus infection.
  • Contraindication for MRI.
  • Pregnant or breast-feeding females or those who plan to become pregnant during the study.
  • Female participants of child-bearing potential not using highly effective contraceptive method (contraception in both female and male was required).

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

Sites / Locations

  • Investigational Site Number :840003
  • Investigational Site Number :840012
  • Investigational Site Number :840002
  • Investigational Site Number :840004
  • Investigational Site Number :056002
  • Investigational Site Number :056001
  • Investigational Site Number :100001
  • Investigational Site Number :124001
  • Investigational Site Number :156001
  • Investigational Site Number :156002
  • Investigational Site Number :156010
  • Investigational Site Number :156006
  • Investigational Site Number :156007
  • Investigational Site Number :156008
  • Investigational Site Number :156005
  • Investigational Site Number :156012
  • Investigational Site Number :156003
  • Investigational Site Number :156004
  • Investigational Site Number :156011
  • Investigational Site Number :156009
  • Investigational Site Number :233001
  • Investigational Site Number :250001
  • Investigational Site Number :250002
  • Investigational Site Number :250003
  • Investigational Site Number :250005
  • Investigational Site Number :300002
  • Investigational Site Number :300001
  • Investigational Site Number :376001
  • Investigational Site Number :376003
  • Investigational Site Number :422001
  • Investigational Site Number :440001
  • Investigational Site Number :504004
  • Investigational Site Number :504005
  • Investigational Site Number :528001
  • Investigational Site Number :620001
  • Investigational Site Number :643001
  • Investigational Site Number :643003
  • Investigational Site Number :643004
  • Investigational Site Number :643005
  • Investigational Site Number :643002
  • Investigational Site Number :688002
  • Investigational Site Number :724002
  • Investigational Site Number :788001
  • Investigational Site Number :788002
  • Investigational Site Number :788004
  • Investigational Site Number :792002
  • Investigational Site Number :792001
  • Investigational Site Number :792006
  • Investigational Site Number :792003
  • Investigational Site Number :792008
  • Investigational Site Number :792007
  • Investigational Site Number :804001
  • Investigational Site Number :804002
  • Investigational Site Number :826001
  • Investigational Site Number :826003

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Teriflunomide

Arm Description

Matching placebo tablets

Teriflunomide oral tablet, three dosages (3.5, 7 or 14 mg) to reach 14 mg adult equivalent

Outcomes

Primary Outcome Measures

Time to First Confirmed Clinical Relapse
Time to first clinical relapse was defined as the duration (in weeks) between randomization and first confirmed clinical relapse. Clinical relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon neurological examination and documented by a standardized, quantified functional system score (FSSs) which included 8 items and items were rated on different scales: brain stem, cerebellar and cerebral functions rated on a scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on a scale of 0 to 6 and ambulation on a scale of 0 to 12, where higher score in each scale indicated worsened neurological function. Confirmed clinical relapse were reviewed and confirmed by an independent Relapse Adjudication Panel (RAP). A participant without confirmed clinical relapse, was considered as clinical relapse free until the end of Week 96.

Secondary Outcome Measures

Probability of Participants Who Were Clinical Relapse Free at Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Participant was considered free of clinical relapse if the participant had no confirmed clinical relapse before treatment discontinuation/completion in 192 weeks treatment period. Clinical relapses: new/recurrent neurological symptoms not associated with fever/infection, lasted at least 24 hours, and accompanied by new objective neurological findings upon neurological examination and documented by standardized, quantified FSSs which included 8 items: rated on different scales: brain stem, cerebellar and cerebral functions rated on scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on scale of 0 to 6 & ambulation on scale of 0 to 12, where higher score in each scale indicated worsened neurological function. New/recurrent symptoms occurred less than 30 days following onset of relapse were considered part of same relapse. Probability of participants who were clinical relapse free at specified weeks were estimated by Kaplan-Meier method and reported.
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan
Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during the 192 weeks treatment period divided by the total number of scans performed during 192 weeks. To account for the different numbers of scans performed among the participants, a negative binomial regression model with robust variance estimation was used. The model included the total number of new or enlarged T2-lesions as the response variable, with treatment group, region, pubertal status and age as covariates and log-transformed number of scans as an offset variable.
Brain Magnetic Resonance Imaging Assessment: Number of T1 Gadolinium (Gd)-Enhancing T1 Lesions Per MRI Scan
The number of T1 Gd-Enhancing lesions per scan was defined as the total number of Gd-enhancing lesions that occurred during the 192 weeks treatment period divided by the total number of scans performed during 192 weeks. To account for the different number of scans performed among the participants, a negative binomial regression model with robust variance estimation was used. The model included the total number of T1-lesions as the response variable, with treatment group, region, pubertal status and age as covariates and log-transformed number of scans as an offset variable.
Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T2 Lesions at Weeks 24, 36, 48, 72, 96, 144 and 192
Volume of T2 lesions was measured by MRI scan.
Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T1 Hypointense Lesions
Volume of T1 hypointense lesions was measured by MRI scan.
Brain Magnetic Resonance Imaging Assessment: Number of New T1 Hypointense Lesions Per MRI Scan
The number of new T1 hypointense lesions were obtained from MRI scans.
Brain Magnetic Resonance Imaging Assessment: Percentage of Participants Free of New or Enlarged MRI T2-Lesions
Percentage of participants who were free of new or enlarged T2 lesions at Weeks 24, 48, 72, 96, 144 and 192 were reported.
Brain Magnetic Resonance Imaging Assessment: Percent Change From Baseline in Brain Volume at Weeks 24, 36, 48, 72, 96, 144 and 192
Percent change from baseline in brain volume (assessed using MRI scans of the Brain) at Weeks 24, 36, 48,72, 96, 144 and 192 was reported.
Cognitive Assessment: Change From Baseline in Total Number of Correct Substitutions Measured by Symbol Digit Modalities Test (SDMT) at Weeks 24, 48, 72, 96, 120, 144, 168 and 192
SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The SDMT score is the number of correct substitution and ranged from 0 (worst outcome) to 110 (best outcome), where higher score indicated better cognitive function.
Cognitive Assessment: Change From Baseline in Number of Completed Items Measured by Symbol Digit Modalities Test at Weeks 24, 48, 72, 96, 120, 144, 168 and 192
SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The SDMT score is the number of completed items and ranged from 0 (worst outcome) to 110 (best outcome), where higher score indicated better cognitive function.
Cognitive Assessment: Change From Baseline in Brief Visuospatial Memory Test-Revised (BVMT-R) Scores at Weeks 96 and 192
The BVMT consists of three trials in which participants must recall shapes by drawing figures on a blank page (response booklet) after being given the opportunity to memorize the figures (given in BMVT-R form) for 10 seconds. BMVT-R form consists of six figures. Points are awarded based on the accuracy of the drawn figure and by correct placement on the blank page. A minimum of 0 to 12 points/scores are awarded per trial, so a participant can score between 0 and 36 points for all three trials (by adding the points/score from each trial), where higher score indicates better outcome.
Cognitive Assessment: Change From Baseline in Trail Making Test- Part A (TMT-A) Test Scores (in Seconds) at Week 96 and 192
'Trail Making Test Part A' is a neuropsychological test of visual attention and task switching. The task requires a participant to 'connect-the-dots' of 25 consecutive numbers (1,2, 3, etc.) in sequential order on a sheet of paper or computer screen. The goal of the participant is to finish the test as quickly as possible, and the time taken to complete the test used as the primary performance metric (in seconds). This is a timed test and the number of seconds to complete the task is recorded. Maximum time allowed is 300 seconds. A lower score indicated better cognitive function.
Cognitive Assessment: Change From Baseline in Trail Making Test B (TMT-B) Test Scores (in Seconds) at Weeks 96 and 192
TMT-B is a cognitive test that gives a measure of various aspects of cognitive performance. It is used to measure cognitive fatigue. The test consisted of 25 circles containing 13 sequential numbers (1 to 13) and 12 sequential letters (A to L) positioned. The test evaluates the time (in seconds) to correctly order letters and numbers in alternate order (1, A, 2, B etc.). Maximum time allowed is 300 seconds, where less time/lower score indicated better cognitive function/performance.
Cognitive Assessment: Change From Baseline in Beery Visual-motor Integration (BVMI) Scores at Weeks 96 and 192
The Beery VMI is a non-verbal assessment that assessed the extent to which individuals can integrate their visual and motor abilities. The participants were provided with geometric designs ranging from simple line drawings to more complex figures and were asked to copy the designs. The test consisted of 24 figures. One point was scored for each successful copy of drawings and no scoring was given when the participant failed to copy the drawings properly. Each successful copying of drawings was summed up and the total was scored on a scale ranged from 0 to 24, where higher score indicated better visual construction skills/better visual and motor abilities and lower score indicated poor visual construction skills/poor visual and motor abilities.
Cognitive Assessment: Change From Baseline in Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Vocabulary Total Raw Scores at Weeks 96 and 192
The WASI-II: Vocabulary test is a quick estimate of an individual's level of intellectual functioning which comprised of 31 total items that required the participant to orally define 3 images and 28 words presented both orally and visually. Items 1 to 3 rated on a score of 0 or 1, items 4 and 5 rated on a score of 0 or 2, items 6 to 31 rated on a scale of 0 to 2. Each item score was summed up to derive the total score which ranged from 0 (minimum score) to 59 (maximum score), where higher score indicated better level of intellectual functioning/higher level of intelligence.
Cognitive Assessment: Change From Baseline in Delis-Kaplan Executive Function System (D-KEFS) Letter Fluency Total Correct Raw Score at Weeks 96 and 192
Letter Fluency is a condition measured in the D-KEFS. Participants were asked to name as many words as they can, starting with a specified letter for 60 seconds. The words cannot be names, places, numbers or grammatical variants of previous answers. Repeated answers were not scored as a correct response. There were 3 trials, with 3 different letters. The total number of correct responses was totaled for all 3 trials and a letter fluency score was given. A higher score was considered better. There was no set range as the score depends on how many correct words the participant relays in the given time period.
Cognitive Assessment: Change From Baseline in Delis-Kaplan Executive Function System Category Fluency Total Correct Raw Score at Weeks 96 and 192
Category Fluency is a condition measured in the D-KEFS. It measured participant's ability to generate words from three different categories (e.g., fruits, vegetables and animals), within a minute for each category. Total score was number of correct words for each category with no points for repetitions or non-words. Score ranged from 0 to unlimited, where 0 = low score, higher score indicated better performance.
Cognitive Assessment - Selective Reminding Test (SRT): Change From Baseline in Total Number of Words on Delayed Recall at Weeks 96 and 192
SRT is a test to assess verbal learning and memory. During the administration of the SRT only the examiner and the participant should be in the testing room. A list of twelve words was read aloud by the examiner at a rate of one word per two seconds. The participant is asked to recall all twelve words after a 30 minute delay. Only the words that were missed on the preceding trial were given in the consecutive trial. The total score represented a sum score of total 6 trials, therefore the score range was from 0 to 72. The lower the score the worse the outcome, higher score indicated better recall.
DB: Pharmacokinetics: Steady-state Trough Concentration (Ctrough) of Teriflunomide
Ctrough was defined as the concentration reached by the drug before the next dose administered. Data for this outcome measure was planned to be collected and analyzed separately for each dose of Teriflunomide. PK samples for teriflunomide 3.5 mg were collected during the first 8 weeks but all participants were switched to teriflunomide 7 mg after Week 8. Hence, plasma concentration of teriflunomide 7 mg and 14 mg were reported.
OL: Time to First Confirmed Clinical Relapse
Time to first clinical relapse was defined as duration (in weeks) after enrollment in OL period and first confirmed clinical relapse. Clinical relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasted at least 24 hours and accompanied by new objective neurological findings upon neurological examination and documented by standardized, quantified FSSs which included 8 items and items were rated on different scales: brain stem, cerebellar & cerebral functions rated on scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on scale of 0 to 6 and ambulation on scale of 0 to 12 where higher score in each scale indicated worsened neurological function. Confirmed clinical relapse were reviewed and confirmed by independent RAP. Participant without confirmed clinical relapse, was considered as clinical relapse free until end of Week 192.
OL: Pharmacokinetics: Steady-state Trough Concentration (Ctrough) of Teriflunomide
Ctrough was defined as the concentration reached by the drug before the next dose is administered. Data for this outcome measure was planned to be collected and analyzed separately for each dose of teriflunomide. PK samples for teriflunomide 3.5 mg were collected during the first 8 weeks but all participants were switched to teriflunomide 7 mg after Week 8. Hence, plasma concentration of teriflunomide 7 mg and 14 mg were reported.

Full Information

First Posted
July 17, 2014
Last Updated
August 30, 2023
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT02201108
Brief Title
Efficacy, Safety and Pharmacokinetics of Teriflunomide in Pediatric Patients With Relapsing Forms of Multiple Sclerosis
Acronym
TERIKIDS
Official Title
A Two Year, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Trial to Evaluate Efficacy, Safety, Tolerability, and Pharmacokinetics of Teriflunomide Administered Orally Once Daily in Pediatric Patients With Relapsing Forms of Multiple Sclerosis Followed by an Open-Label Extension
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 16, 2014 (Actual)
Primary Completion Date
October 25, 2019 (Actual)
Study Completion Date
June 25, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Primary Objective: To assess the effect of teriflunomide in comparison to placebo on disease activity measured by time to first clinical relapse after randomization in children and adolescents 10 to 17 years of age with relapsing forms of multiple sclerosis (MS). Secondary Objective: To assess the effect of teriflunomide in comparison to placebo on disease activity/progression measured by brain magnetic resonance imaging (MRI) and on cognitive function. To evaluate the safety and tolerability of teriflunomide in comparison to placebo. To evaluate the pharmacokinetics (PK) of teriflunomide.
Detailed Description
The study duration included a screening period up to 4 weeks, a double-blind treatment period of up to 96 weeks, an open-label period which included the remainder of the initial 96 weeks, where applicable, and a 96-week extension, i.e., up to a maximum of 192 weeks after randomization. There was a follow-up period of 4 weeks for participants discontinuing treatment. Within the 96 weeks double-blind treatment period, the first 4 weeks were PK run-in phase in which PK samples (blood samples) were collected from participants and then 4 weeks of analysis (no samples drawn). The PK run-in phase (total 8 weeks) was intended to provide individual PK parameters to allow the dose adjustment to the 14 milligrams (mg) adult-equivalent dose for the rest of the study. Participants who experienced a relapse after the PK run-in phase (8 weeks) and confirmed by the Relapse Adjudication Panel and participants who fulfilled MRI criteria (high number of new lesions at weeks 36, 48 or 72 compared to previous images) had the option to continue in an open-label teriflunomide treatment arm up to 192 weeks from randomization. An optional additional extension period is available for young participants with teriflunomide until the participants are 18 years old and/or able to switch to commercial product, whichever comes first.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
166 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo tablets
Arm Title
Teriflunomide
Arm Type
Experimental
Arm Description
Teriflunomide oral tablet, three dosages (3.5, 7 or 14 mg) to reach 14 mg adult equivalent
Intervention Type
Drug
Intervention Name(s)
Teriflunomide
Other Intervention Name(s)
AUBAGIO, HMR1726
Intervention Description
Pharmaceutical form:film-coated tablet, Route of administration: oral
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Pharmaceutical form:tablet, Route of administration: oral
Primary Outcome Measure Information:
Title
Time to First Confirmed Clinical Relapse
Description
Time to first clinical relapse was defined as the duration (in weeks) between randomization and first confirmed clinical relapse. Clinical relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon neurological examination and documented by a standardized, quantified functional system score (FSSs) which included 8 items and items were rated on different scales: brain stem, cerebellar and cerebral functions rated on a scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on a scale of 0 to 6 and ambulation on a scale of 0 to 12, where higher score in each scale indicated worsened neurological function. Confirmed clinical relapse were reviewed and confirmed by an independent Relapse Adjudication Panel (RAP). A participant without confirmed clinical relapse, was considered as clinical relapse free until the end of Week 96.
Time Frame
Baseline up to Week 96
Secondary Outcome Measure Information:
Title
Probability of Participants Who Were Clinical Relapse Free at Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Description
Participant was considered free of clinical relapse if the participant had no confirmed clinical relapse before treatment discontinuation/completion in 192 weeks treatment period. Clinical relapses: new/recurrent neurological symptoms not associated with fever/infection, lasted at least 24 hours, and accompanied by new objective neurological findings upon neurological examination and documented by standardized, quantified FSSs which included 8 items: rated on different scales: brain stem, cerebellar and cerebral functions rated on scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on scale of 0 to 6 & ambulation on scale of 0 to 12, where higher score in each scale indicated worsened neurological function. New/recurrent symptoms occurred less than 30 days following onset of relapse were considered part of same relapse. Probability of participants who were clinical relapse free at specified weeks were estimated by Kaplan-Meier method and reported.
Time Frame
Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Title
Brain Magnetic Resonance Imaging (MRI) Assessment: Number of New or Enlarged T2 Lesions Per MRI Scan
Description
Number of new or enlarged T2 lesions per scan was defined as the total number of new or enlarged T2 lesion that occurred during the 192 weeks treatment period divided by the total number of scans performed during 192 weeks. To account for the different numbers of scans performed among the participants, a negative binomial regression model with robust variance estimation was used. The model included the total number of new or enlarged T2-lesions as the response variable, with treatment group, region, pubertal status and age as covariates and log-transformed number of scans as an offset variable.
Time Frame
Baseline up to Week 192
Title
Brain Magnetic Resonance Imaging Assessment: Number of T1 Gadolinium (Gd)-Enhancing T1 Lesions Per MRI Scan
Description
The number of T1 Gd-Enhancing lesions per scan was defined as the total number of Gd-enhancing lesions that occurred during the 192 weeks treatment period divided by the total number of scans performed during 192 weeks. To account for the different number of scans performed among the participants, a negative binomial regression model with robust variance estimation was used. The model included the total number of T1-lesions as the response variable, with treatment group, region, pubertal status and age as covariates and log-transformed number of scans as an offset variable.
Time Frame
Baseline up to Week 192
Title
Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T2 Lesions at Weeks 24, 36, 48, 72, 96, 144 and 192
Description
Volume of T2 lesions was measured by MRI scan.
Time Frame
Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192
Title
Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T1 Hypointense Lesions
Description
Volume of T1 hypointense lesions was measured by MRI scan.
Time Frame
Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192
Title
Brain Magnetic Resonance Imaging Assessment: Number of New T1 Hypointense Lesions Per MRI Scan
Description
The number of new T1 hypointense lesions were obtained from MRI scans.
Time Frame
Baseline up to Week 192
Title
Brain Magnetic Resonance Imaging Assessment: Percentage of Participants Free of New or Enlarged MRI T2-Lesions
Description
Percentage of participants who were free of new or enlarged T2 lesions at Weeks 24, 48, 72, 96, 144 and 192 were reported.
Time Frame
Baseline, Weeks 24, 48, 72, 96, 144 and 192
Title
Brain Magnetic Resonance Imaging Assessment: Percent Change From Baseline in Brain Volume at Weeks 24, 36, 48, 72, 96, 144 and 192
Description
Percent change from baseline in brain volume (assessed using MRI scans of the Brain) at Weeks 24, 36, 48,72, 96, 144 and 192 was reported.
Time Frame
Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192
Title
Cognitive Assessment: Change From Baseline in Total Number of Correct Substitutions Measured by Symbol Digit Modalities Test (SDMT) at Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Description
SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The SDMT score is the number of correct substitution and ranged from 0 (worst outcome) to 110 (best outcome), where higher score indicated better cognitive function.
Time Frame
Baseline, DB period: Weeks 24, 48, 72 and 96; OL period: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Title
Cognitive Assessment: Change From Baseline in Number of Completed Items Measured by Symbol Digit Modalities Test at Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Description
SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The SDMT score is the number of completed items and ranged from 0 (worst outcome) to 110 (best outcome), where higher score indicated better cognitive function.
Time Frame
Baseline, DB period: Weeks 24, 48, 72 and 96; OL period: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
Title
Cognitive Assessment: Change From Baseline in Brief Visuospatial Memory Test-Revised (BVMT-R) Scores at Weeks 96 and 192
Description
The BVMT consists of three trials in which participants must recall shapes by drawing figures on a blank page (response booklet) after being given the opportunity to memorize the figures (given in BMVT-R form) for 10 seconds. BMVT-R form consists of six figures. Points are awarded based on the accuracy of the drawn figure and by correct placement on the blank page. A minimum of 0 to 12 points/scores are awarded per trial, so a participant can score between 0 and 36 points for all three trials (by adding the points/score from each trial), where higher score indicates better outcome.
Time Frame
Baseline, Weeks 96 and 192
Title
Cognitive Assessment: Change From Baseline in Trail Making Test- Part A (TMT-A) Test Scores (in Seconds) at Week 96 and 192
Description
'Trail Making Test Part A' is a neuropsychological test of visual attention and task switching. The task requires a participant to 'connect-the-dots' of 25 consecutive numbers (1,2, 3, etc.) in sequential order on a sheet of paper or computer screen. The goal of the participant is to finish the test as quickly as possible, and the time taken to complete the test used as the primary performance metric (in seconds). This is a timed test and the number of seconds to complete the task is recorded. Maximum time allowed is 300 seconds. A lower score indicated better cognitive function.
Time Frame
Baseline, Weeks 96 and 192
Title
Cognitive Assessment: Change From Baseline in Trail Making Test B (TMT-B) Test Scores (in Seconds) at Weeks 96 and 192
Description
TMT-B is a cognitive test that gives a measure of various aspects of cognitive performance. It is used to measure cognitive fatigue. The test consisted of 25 circles containing 13 sequential numbers (1 to 13) and 12 sequential letters (A to L) positioned. The test evaluates the time (in seconds) to correctly order letters and numbers in alternate order (1, A, 2, B etc.). Maximum time allowed is 300 seconds, where less time/lower score indicated better cognitive function/performance.
Time Frame
Baseline, Weeks 96 and 192
Title
Cognitive Assessment: Change From Baseline in Beery Visual-motor Integration (BVMI) Scores at Weeks 96 and 192
Description
The Beery VMI is a non-verbal assessment that assessed the extent to which individuals can integrate their visual and motor abilities. The participants were provided with geometric designs ranging from simple line drawings to more complex figures and were asked to copy the designs. The test consisted of 24 figures. One point was scored for each successful copy of drawings and no scoring was given when the participant failed to copy the drawings properly. Each successful copying of drawings was summed up and the total was scored on a scale ranged from 0 to 24, where higher score indicated better visual construction skills/better visual and motor abilities and lower score indicated poor visual construction skills/poor visual and motor abilities.
Time Frame
Baseline, Weeks 96 and 192
Title
Cognitive Assessment: Change From Baseline in Wechsler Abbreviated Scale of Intelligence-II (WASI-II) Vocabulary Total Raw Scores at Weeks 96 and 192
Description
The WASI-II: Vocabulary test is a quick estimate of an individual's level of intellectual functioning which comprised of 31 total items that required the participant to orally define 3 images and 28 words presented both orally and visually. Items 1 to 3 rated on a score of 0 or 1, items 4 and 5 rated on a score of 0 or 2, items 6 to 31 rated on a scale of 0 to 2. Each item score was summed up to derive the total score which ranged from 0 (minimum score) to 59 (maximum score), where higher score indicated better level of intellectual functioning/higher level of intelligence.
Time Frame
Baseline, Weeks 96 and 192
Title
Cognitive Assessment: Change From Baseline in Delis-Kaplan Executive Function System (D-KEFS) Letter Fluency Total Correct Raw Score at Weeks 96 and 192
Description
Letter Fluency is a condition measured in the D-KEFS. Participants were asked to name as many words as they can, starting with a specified letter for 60 seconds. The words cannot be names, places, numbers or grammatical variants of previous answers. Repeated answers were not scored as a correct response. There were 3 trials, with 3 different letters. The total number of correct responses was totaled for all 3 trials and a letter fluency score was given. A higher score was considered better. There was no set range as the score depends on how many correct words the participant relays in the given time period.
Time Frame
Baseline, Weeks 96 and 192
Title
Cognitive Assessment: Change From Baseline in Delis-Kaplan Executive Function System Category Fluency Total Correct Raw Score at Weeks 96 and 192
Description
Category Fluency is a condition measured in the D-KEFS. It measured participant's ability to generate words from three different categories (e.g., fruits, vegetables and animals), within a minute for each category. Total score was number of correct words for each category with no points for repetitions or non-words. Score ranged from 0 to unlimited, where 0 = low score, higher score indicated better performance.
Time Frame
Baseline, Weeks 96 and 192
Title
Cognitive Assessment - Selective Reminding Test (SRT): Change From Baseline in Total Number of Words on Delayed Recall at Weeks 96 and 192
Description
SRT is a test to assess verbal learning and memory. During the administration of the SRT only the examiner and the participant should be in the testing room. A list of twelve words was read aloud by the examiner at a rate of one word per two seconds. The participant is asked to recall all twelve words after a 30 minute delay. Only the words that were missed on the preceding trial were given in the consecutive trial. The total score represented a sum score of total 6 trials, therefore the score range was from 0 to 72. The lower the score the worse the outcome, higher score indicated better recall.
Time Frame
Baseline, Weeks 96 and 192
Title
DB: Pharmacokinetics: Steady-state Trough Concentration (Ctrough) of Teriflunomide
Description
Ctrough was defined as the concentration reached by the drug before the next dose administered. Data for this outcome measure was planned to be collected and analyzed separately for each dose of Teriflunomide. PK samples for teriflunomide 3.5 mg were collected during the first 8 weeks but all participants were switched to teriflunomide 7 mg after Week 8. Hence, plasma concentration of teriflunomide 7 mg and 14 mg were reported.
Time Frame
Predose on Week 36
Title
OL: Time to First Confirmed Clinical Relapse
Description
Time to first clinical relapse was defined as duration (in weeks) after enrollment in OL period and first confirmed clinical relapse. Clinical relapses were defined as new or recurrent neurological symptoms not associated with fever or infection, lasted at least 24 hours and accompanied by new objective neurological findings upon neurological examination and documented by standardized, quantified FSSs which included 8 items and items were rated on different scales: brain stem, cerebellar & cerebral functions rated on scale of 0 to 5; visual, pyramidal, sensory and bowel/bladder rated on scale of 0 to 6 and ambulation on scale of 0 to 12 where higher score in each scale indicated worsened neurological function. Confirmed clinical relapse were reviewed and confirmed by independent RAP. Participant without confirmed clinical relapse, was considered as clinical relapse free until end of Week 192.
Time Frame
Baseline up to Week 192
Title
OL: Pharmacokinetics: Steady-state Trough Concentration (Ctrough) of Teriflunomide
Description
Ctrough was defined as the concentration reached by the drug before the next dose is administered. Data for this outcome measure was planned to be collected and analyzed separately for each dose of teriflunomide. PK samples for teriflunomide 3.5 mg were collected during the first 8 weeks but all participants were switched to teriflunomide 7 mg after Week 8. Hence, plasma concentration of teriflunomide 7 mg and 14 mg were reported.
Time Frame
Pre-dose at Week 36

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Participants with relapsing MS were eligible. Participants who met the criteria of MS based on McDonald criteria 2010 and International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric MS, version of 2012 and had: at least one relapse (or attack) in the 12 months preceding screening or, at least two relapses (or attack) in the 24 months preceding screening. Less than 18 years of age and greater than or equal to (>=) 10 years of age at randomization. Specific for the Russian Federation from 18 December 2014 to 26 July 2016, less than or equal to 17 years of age and >= 13 years of age at randomization. Signed informed consent/assent obtained from participant and participant's legal representative (parents or guardians) according to local regulations. Exclusion criteria: Expanded disability status scale score greater than 5.5 at screening or randomization visits. Relapse within 30 days prior to randomization. Treated with: glatiramer acetate, interferons, or dimethyl fumarate within 1 month prior to randomization. fingolimod, or intravenous immunoglobulins within 3 months prior to randomization. natalizumab, other immunosuppressant or immunomodulatory agents such as cyclophosphamide, azathioprine, cyclosporine, methotrexate, mycophenolate, within 6 months prior to randomization. cladribine or mitoxantrone within 2 years prior to randomization. Treated with alemtuzumab at any time. History of human immunodeficiency virus infection. Contraindication for MRI. Pregnant or breast-feeding females or those who plan to become pregnant during the study. Female participants of child-bearing potential not using highly effective contraceptive method (contraception in both female and male was required). The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number :840003
City
Cullman
State/Province
Alabama
ZIP/Postal Code
35058
Country
United States
Facility Name
Investigational Site Number :840012
City
Tampa
State/Province
Florida
ZIP/Postal Code
33609-4052
Country
United States
Facility Name
Investigational Site Number :840002
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Investigational Site Number :840004
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Investigational Site Number :056002
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Investigational Site Number :056001
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Investigational Site Number :100001
City
Sofia
ZIP/Postal Code
1113
Country
Bulgaria
Facility Name
Investigational Site Number :124001
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3B 6A8
Country
Canada
Facility Name
Investigational Site Number :156001
City
Beijing
ZIP/Postal Code
100034
Country
China
Facility Name
Investigational Site Number :156002
City
Beijing
ZIP/Postal Code
100045
Country
China
Facility Name
Investigational Site Number :156010
City
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Investigational Site Number :156006
City
Changchun
ZIP/Postal Code
130021
Country
China
Facility Name
Investigational Site Number :156007
City
Changsha
ZIP/Postal Code
410011
Country
China
Facility Name
Investigational Site Number :156008
City
Chengdu
ZIP/Postal Code
610041
Country
China
Facility Name
Investigational Site Number :156005
City
Chongqing
ZIP/Postal Code
400014
Country
China
Facility Name
Investigational Site Number :156012
City
Guangzhou
ZIP/Postal Code
510630
Country
China
Facility Name
Investigational Site Number :156003
City
Shanghai
ZIP/Postal Code
200092
Country
China
Facility Name
Investigational Site Number :156004
City
Shanghai
ZIP/Postal Code
201102
Country
China
Facility Name
Investigational Site Number :156011
City
Shijiazhuang
ZIP/Postal Code
050000
Country
China
Facility Name
Investigational Site Number :156009
City
Taiyuan
ZIP/Postal Code
030001
Country
China
Facility Name
Investigational Site Number :233001
City
Tallinn
ZIP/Postal Code
10617
Country
Estonia
Facility Name
Investigational Site Number :250001
City
Le Kremlin Bicetre
ZIP/Postal Code
94270
Country
France
Facility Name
Investigational Site Number :250002
City
Lyon Cedex 03
ZIP/Postal Code
69394
Country
France
Facility Name
Investigational Site Number :250003
City
Rennes Cedex
ZIP/Postal Code
35033
Country
France
Facility Name
Investigational Site Number :250005
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Investigational Site Number :300002
City
Athens
ZIP/Postal Code
115 27
Country
Greece
Facility Name
Investigational Site Number :300001
City
Thessaloniki
ZIP/Postal Code
54642
Country
Greece
Facility Name
Investigational Site Number :376001
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Investigational Site Number :376003
City
Tel HaShomer
ZIP/Postal Code
52621
Country
Israel
Facility Name
Investigational Site Number :422001
City
Beirut
Country
Lebanon
Facility Name
Investigational Site Number :440001
City
Kaunas
ZIP/Postal Code
50161
Country
Lithuania
Facility Name
Investigational Site Number :504004
City
FES
Country
Morocco
Facility Name
Investigational Site Number :504005
City
Marrakech
ZIP/Postal Code
40000
Country
Morocco
Facility Name
Investigational Site Number :528001
City
Rotterdam
ZIP/Postal Code
3015 CN
Country
Netherlands
Facility Name
Investigational Site Number :620001
City
Coimbra
ZIP/Postal Code
3000-075
Country
Portugal
Facility Name
Investigational Site Number :643001
City
Moscow
ZIP/Postal Code
127566
Country
Russian Federation
Facility Name
Investigational Site Number :643003
City
Nizhny Novgorod
ZIP/Postal Code
603155
Country
Russian Federation
Facility Name
Investigational Site Number :643004
City
Novosibirsk
ZIP/Postal Code
630087
Country
Russian Federation
Facility Name
Investigational Site Number :643005
City
Saint-Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Investigational Site Number :643002
City
Saint-Petersburg
ZIP/Postal Code
197110
Country
Russian Federation
Facility Name
Investigational Site Number :688002
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Investigational Site Number :724002
City
Murcia
ZIP/Postal Code
30120
Country
Spain
Facility Name
Investigational Site Number :788001
City
La Manouba
ZIP/Postal Code
2020
Country
Tunisia
Facility Name
Investigational Site Number :788002
City
Sfax
ZIP/Postal Code
3029
Country
Tunisia
Facility Name
Investigational Site Number :788004
City
Sfax
ZIP/Postal Code
3029
Country
Tunisia
Facility Name
Investigational Site Number :792002
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Investigational Site Number :792001
City
Ankara
ZIP/Postal Code
06500
Country
Turkey
Facility Name
Investigational Site Number :792006
City
Istanbul
ZIP/Postal Code
34390
Country
Turkey
Facility Name
Investigational Site Number :792003
City
Istanbul
ZIP/Postal Code
34688
Country
Turkey
Facility Name
Investigational Site Number :792008
City
Izmir
ZIP/Postal Code
35210
Country
Turkey
Facility Name
Investigational Site Number :792007
City
İzmir
Country
Turkey
Facility Name
Investigational Site Number :804001
City
Kharkiv
ZIP/Postal Code
61068
Country
Ukraine
Facility Name
Investigational Site Number :804002
City
Kharkiv
ZIP/Postal Code
61068
Country
Ukraine
Facility Name
Investigational Site Number :826001
City
London
State/Province
London, City Of
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Facility Name
Investigational Site Number :826003
City
Birmingham
ZIP/Postal Code
B4 6NH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Citations:
PubMed Identifier
34800398
Citation
Chitnis T, Banwell B, Kappos L, Arnold DL, Gucuyener K, Deiva K, Skripchenko N, Cui LY, Saubadu S, Hu W, Benamor M, Le-Halpere A, Truffinet P, Tardieu M; TERIKIDS Investigators. Safety and efficacy of teriflunomide in paediatric multiple sclerosis (TERIKIDS): a multicentre, double-blind, phase 3, randomised, placebo-controlled trial. Lancet Neurol. 2021 Dec;20(12):1001-1011. doi: 10.1016/S1474-4422(21)00364-1.
Results Reference
derived

Learn more about this trial

Efficacy, Safety and Pharmacokinetics of Teriflunomide in Pediatric Patients With Relapsing Forms of Multiple Sclerosis

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