Efficacy, Safety and Pharmacokinetics of Teriflunomide in... | NCT02201108 | Trialant
NCT02201108
Sponsor
Genzyme, a Sanofi Company
Status
Completed
Last Update Posted
Feb 6, 2025Actual
Enrollment
166Actual
Phase
Phase 3
Conditions
Multiple Sclerosis
Interventions
Teriflunomide
Placebo
Countries
United States
Belgium
Bulgaria
Canada
China
Estonia
France
Greece
Israel
Lebanon
Lithuania
Morocco
Netherlands
North Macedonia
Portugal
Russia
Serbia
Spain
Tunisia
Turkey (Türkiye)
Ukraine
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02201108
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
EFC11759
Secondary IDs
ID
Type
Description
Link
U1111-1124-0983
Registry Identifier
ICTRP
2011-005249-12
EudraCT Number
Brief Title
Efficacy, Safety and Pharmacokinetics of Teriflunomide in Pediatric Patients With Relapsing Forms of Multiple Sclerosis
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
Acronym
TERIKIDS
Organization
SanofiINDUSTRY
Status Module
Record Verification Date
Jan 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jul 16, 2014Actual
Primary Completion Date
Oct 25, 2019Actual
Completion Date
Jul 29, 2024Actual
First Submitted Date
Jul 17, 2014
First Submission Date that Met QC Criteria
Jul 24, 2014
First Posted Date
Jul 25, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Oct 20, 2020
Results First Submitted that Met QC Criteria
Nov 27, 2020
Results First Posted Date
Nov 30, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jan 14, 2025
Last Update Posted Date
Feb 6, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Genzyme, a Sanofi CompanyINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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 was available for young participants with teriflunomide until the participants are 18 years old and/or able to switch to commercial product, whichever comes first.
Conditions Module
Conditions
Multiple Sclerosis
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
166Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo
Placebo Comparator
Matching placebo tablets
Drug: Placebo
Teriflunomide
Experimental
Teriflunomide oral tablet, three dosages (3.5, 7 or 14 mg) to reach 14 mg adult equivalent
Drug: Teriflunomide
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Teriflunomide
Drug
Pharmaceutical form:film-coated tablet, Route of administration: oral
Teriflunomide
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
Baseline up to Week 96
Secondary Outcomes
Measure
Description
Time Frame
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.
Other Outcomes
Not provided
Eligibility Module
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.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
10 Years
Maximum Age
17 Years
Standard Ages
Child
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Clinical Sciences & Operations
Sanofi
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
North Central Neurology Associates, PC Site Number : 840003
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
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Participants were randomly assigned to receive either teriflunomide or placebo in a 2:1 ratio via Interactive Voice Response System. Randomization was stratified by the country and participant's pubertal status.
Recruitment Details
Study was conducted at 57 active centers in 21 countries. A total of 185 participants were screened between 16 July 2014 and 27 December 2017, of which 166 participants were enrolled and randomized. A total of 19 participants failed screening mainly due to meeting exclusion criteria.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in double blind (DB) treatment period. After completion of DB period, eligible participants entered in open label (OL) period and received 1 teriflunomide tablet, 3.5 milligrams (mg) (in case of body weight [BW] up to 40 kilograms [kg]) or 7 mg (BW greater than [>] 40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was less than or equal to (<=) 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg).The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as maximum concentration observed (Cmax) ranging from 8.03 to 49.10 micrograms per milliliter (mcg/mL) and area under the curve from time 0 hour to 24 hours (AUC0-24) ranging from 184 to 1160 micrograms*hour per milliliter (mcg*h/mL).
Pharmaceutical form:tablet, Route of administration: oral
Placebo
Weeks 24, 48, 72, 96, 120, 144, 168 and 192
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.
Baseline up to Week 192
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.
Baseline up to Week 192
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.
Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192
Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T1 Hypointense Lesions
Volume of T1 hypointense lesions was measured by MRI scan.
Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192
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.
Baseline up to Week 192
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.
Baseline, Weeks 24, 48, 72, 96, 144 and 192
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.
Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192
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.
Baseline, DB period: Weeks 24, 48, 72 and 96; OL period: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
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.
Baseline, DB period: Weeks 24, 48, 72 and 96; OL period: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
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.
Baseline, Weeks 96 and 192
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.
Baseline, Weeks 96 and 192
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.
Baseline, Weeks 96 and 192
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.
Baseline, Weeks 96 and 192
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.
Baseline, Weeks 96 and 192
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.
Baseline, Weeks 96 and 192
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.
Baseline, Weeks 96 and 192
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.
Baseline, Weeks 96 and 192
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.
Predose on Week 36
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.
Baseline up to 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.
Pre-dose at Week 36
Axiom Clinical Research of Florida Site Number : 840012
Tampa
Florida
33609-4052
United States
Massachusetts General Hospital Site Number : 840002
Boston
Massachusetts
02114
United States
Raleigh Neurology Associates Site Number : 840004
Raleigh
North Carolina
27607
United States
Investigational Site Number : 056002
Ghent
9000
Belgium
Investigational Site Number : 056001
Leuven
3000
Belgium
Investigational Site Number : 100001
Sofia
1113
Bulgaria
Investigational Site Number : 124001
Calgary
Alberta
T3B 6A8
Canada
Investigational Site Number : 156001
Beijing
100034
China
Investigational Site Number : 156002
Beijing
100045
China
Investigational Site Number : 156010
Beijing
100730
China
Investigational Site Number : 156006
Changchun
130021
China
Investigational Site Number : 156007
Changsha
410011
China
Investigational Site Number : 156008
Chengdu
610041
China
Investigational Site Number : 156005
Chongqing
400014
China
Investigational Site Number : 156012
Guangzhou
510630
China
Investigational Site Number : 156003
Shanghai
200092
China
Investigational Site Number : 156004
Shanghai
201102
China
Investigational Site Number : 156011
Shijiazhuang
050000
China
Investigational Site Number : 156009
Taiyuan
030001
China
Investigational Site Number : 233001
Tallinn
10617
Estonia
Investigational Site Number : 250001
Le Kremlin-Bicêtre
94270
France
Investigational Site Number : 250002
Lyon
69394
France
Investigational Site Number : 250003
Rennes
35033
France
Investigational Site Number : 250005
Toulouse
31059
France
Investigational Site Number : 300002
Athens
115 27
Greece
Investigational Site Number : 300001
Thessaloniki
54642
Greece
Investigational Site Number : 376001
Jerusalem
91120
Israel
Investigational Site Number : 376003
Tel Litwinsky
52621
Israel
Investigational Site Number : 422001
Beirut
11-0236
Lebanon
Investigational Site Number : 440001
Kaunas
50161
Lithuania
Investigational Site Number : 504004
Fes
Morocco
Investigational Site Number : 504005
Marrakesh
40000
Morocco
Investigational Site Number : 528001
Rotterdam
3015 CN
Netherlands
Investigational Site Number : 807002
Shtip
2000
North Macedonia
Investigational Site Number : 807001
Skopje
1000
North Macedonia
Investigational Site Number : 620001
Coimbra
3000-075
Portugal
Investigational Site Number : 643001
Moscow
127566
Russia
Investigational Site Number : 643003
Nizhny Novgorod
603155
Russia
Investigational Site Number : 643004
Novosibirsk
630087
Russia
Investigational Site Number : 643005
Saint Petersburg
197022
Russia
Investigational Site Number : 643002
Saint Petersburg
197110
Russia
Investigational Site Number : 688002
Belgrade
11000
Serbia
Investigational Site Number : 724002
Murcia
30120
Spain
Investigational Site Number : 788001
Manouba
2020
Tunisia
Investigational Site Number : 788002
Sfax
3029
Tunisia
Investigational Site Number : 788004
Sfax
3029
Tunisia
Investigational Site Number : 792002
Ankara
06100
Turkey (Türkiye)
Investigational Site Number : 792001
Ankara
06500
Turkey (Türkiye)
Investigational Site Number : 792006
Istanbul
34390
Turkey (Türkiye)
Investigational Site Number : 792003
Istanbul
34688
Turkey (Türkiye)
Investigational Site Number : 792008
Izmir
35210
Turkey (Türkiye)
Investigational Site Number : 792007
Izmir
Turkey (Türkiye)
Investigational Site Number : 804001
Kharkiv
61068
Ukraine
Investigational Site Number : 804002
Kharkiv
61068
Ukraine
Investigational Site Number : 826001
London
London, City of
SE1 7EH
United Kingdom
Investigational Site Number : 826003
Birmingham
B4 6NH
United Kingdom
Derived
Kuhle J, Chitnis T, Banwell B, Tardieu M, Arnold DL, Rawlings AM, Geertsen SS, Lublin AL, Saubadu S, Truffinet P, Kappos L. Plasma neurofilament light chain in children with relapsing MS receiving teriflunomide or placebo: A post hoc analysis of the randomized TERIKIDS trial. Mult Scler. 2023 Mar;29(3):385-394. doi: 10.1177/13524585221144742. Epub 2023 Jan 12.
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.
FG001
Teriflunomide/Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
FG002
Teriflunomide
Participants who were not adults when they completed the 192-week OL period were offered an optional additional extension period to receive 1 teriflunomide tablet 14 mg daily (or every other day if BW was <40 kg) until they became adults or until they were able to switch to the commercial product, whichever came first.
FG00057 subjects
FG001109 subjects
FG0020 subjects
COMPLETED
FG00053 subjects
FG001102 subjects
FG0020 subjects
NOT COMPLETED
FG0004 subjects
FG0017 subjects
FG0020 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0016 subjects
FG0020 subjects
Lack of Efficacy
FG0002 subjects
FG0011 subjects
FG0020 subjects
Withdrawal by Subject
FG0002 subjects
FG0010 subjects
FG0020 subjects
Open Label Period (up to Week 192)
Type
Comment
Milestone Data
STARTED
Post completion of DB treatment period, only eligible participants entered OL treatment period.
FG00052 subjects
FG001100 subjects
FG0020 subjects
COMPLETED
FG00031 subjects
FG00173 subjects
FG0020 subjects
NOT COMPLETED
FG00021 subjects
FG00127 subjects
FG0020 subjects
Type
Comment
Reasons
Lack of Efficacy
FG00010 subjects
FG00114 subjects
FG0020 subjects
Poor compliance to protocol
FG000
Extension Period (Up to Week 492)
Type
Comment
Milestone Data
STARTED
Post completion of OL treatment period, only eligible participants entered extension period.
FG0000 subjects
FG0010 subjects
FG00227 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG00224 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0023 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0022 subjects
Poor compliance to protocol
FG000
Analysis was performed on all randomized participants.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
BG001
Teriflunomide/Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
BG002
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00057
BG001109
BG002166
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00014.7± 2.1
BG00114.6± 2.0
BG00214.6± 2.0
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00039
BG00172
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Race
Title
Measurements
Caucasian/White
BG00042
BG00175
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
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.
Analysis was performed on Intent-to-treat (ITT) population, which consisted of all randomized participants analyzed according to the treatment allocated by randomization.
Posted
Median
Full Range
weeks
Baseline up to Week 96
ID
Title
Description
OG000
Double-Blind Treatment Period: Placebo
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB period.
OG001
Double-Blind Treatment Period: Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily: 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL in DB period.
Units
Counts
Participants
OG00057
OG001109
Title
Denominators
Categories
Title
Measurements
OG00039.14(0.1 to 98.0)
OG00175.29(0.1 to 98.7)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Stratified Log-Rank test
P-value derived from log-rank test with stratification of region and pubertal status.
0.2949
Threshold for significance was < 0.05.
Hazard Ratio (HR)
0.657
2-Sided
95
0.388
1.113
Hazard ratio was estimated using a Cox proportional-hazards model with factors for treatment group, region, pubertal status, age, and number of relapses in the year prior to randomization as covariates and with robust variance estimation.
Superiority
Secondary
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.
Analysis was performed on efficacy population which included all participants enrolled and treated with at least 1 dose of teriflunomide in OL period analyzed according to the treatment group allocated by randomization in the DB period.
Posted
Number
95% Confidence Interval
probability of relapse free participants
Weeks 24, 48, 72, 96, 120, 144, 168 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population.
Posted
Number
95% Confidence Interval
lesions per scan
Baseline up to Week 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population.
Posted
Number
95% Confidence Interval
lesions per scan
Baseline up to Week 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
milliliters
Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
Brain Magnetic Resonance Imaging Assessment: Change From Baseline in Volume of T1 Hypointense Lesions
Volume of T1 hypointense lesions was measured by MRI scan.
Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
milliliters
Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population.
Posted
Number
lesions
Baseline up to Week 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Secondary
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.
Analysis was performed on efficacy population.
Posted
Number
percentage of participants
Baseline, Weeks 24, 48, 72, 96, 144 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
OG001
Teriflunomide/ Teriflunomide
Secondary
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.
Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
percent change
Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
score on a scale
Baseline, DB period: Weeks 24, 48, 72 and 96; OL period: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
score on a scale
Baseline, DB period: Weeks 24, 48, 72 and 96; OL period: Weeks 24, 48, 72, 96, 120, 144, 168 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Weeks 96 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
seconds
Baseline, Weeks 96 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
seconds
Baseline, Weeks 96 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Weeks 96 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population. Here, "overall number of participants analyzed" = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Weeks 96 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population. Here, "overall number of participants analyzed" = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Weeks 96 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population. Here, "overall number of participants analyzed" = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Weeks 96 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on efficacy population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
Posted
Mean
Standard Deviation
score on a scale
Baseline, Weeks 96 and 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on PK population which included all randomized participants exposed to DB study medication and had at least 1 PK sample taken. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and "0'' signifies that none of the participant was evaluable for Teriflunomide 3.5 mg arm.
Posted
Mean
Standard Deviation
micrograms per milliliter
Predose on Week 36
ID
Title
Description
OG000
Teriflunomide 3.5 mg
Participants with BW up to 40 kg received 1 teriflunomide tablet, 3.5 mg orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW <= 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg).
Secondary
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.
Analysis was performed on efficacy population.
Posted
Median
Full Range
weeks
Baseline up to Week 192
ID
Title
Description
OG000
Placebo/Teriflunomide
Participants received Placebo matching to teriflunomide tablet orally once daily for 96 weeks in DB treatment period. After completion of DB period, eligible participants entered in OL period and received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) for first 8 weeks. After 8 weeks if individual predicted PK parameter was <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW>40 kg) in the OL period for additional 96 weeks (i.e., up to Week 192). If individual predicted PK parameters >95th percentile of adult range then participant received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Secondary
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.
Analysis was performed on PK population which included all randomized participants exposed to study medication, regardless of the amount of treatment administered who had at least one PK sample taken in OL period. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and "0'' signifies that none of the participant was evaluable for Placebo/Teriflunomide 3.5 mg and Teriflunomide/Teriflunomide 3.5 mg arms.
Posted
Mean
Standard Deviation
micrograms per milliliter
Pre-dose at Week 36
ID
Title
Description
OG000
Placebo / Teriflunomide 3.5 mg
Participants previously treated with placebo in DB period received 1 teriflunomide tablet 3.5 mg orally once daily for first 8 weeks of OL period. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to Week 192: if predicted PK parameters <= 95th percentile of adult range then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg).
Time Frame
Treatment-emergent adverse events (TEAEs), treatment-emergent serious AEs and deaths were collected from first dose of study drug (Day 1) up to 96 weeks (for DB period arms), first dose of study drug in OL period (Week 97) up to Week 192 (for OL period arms) and first dose of study drug in extension period (Week 193) up to Week 492 (for extension period arm).
Description
Safety population included all randomized participants exposed to study medication, regardless of the amount of treatment administered.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Double-Blind Treatment Period: Placebo
Participants received placebo matching to teriflunomide tablet orally QD for 96 weeks.
0
57
6
57
42
57
EG001
Double-Blind Treatment Period: Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally QD for 8 weeks. After 8 weeks, based on participants predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <=95th percentile of adult range after 7 mg QD: 1 tablet of 7 mg daily (for BW up to 40 kg) or 1 tablet of14 mg daily (for BW>40 kg); or if predicted PK parameters >95th percentile of adult range:1 tablet of 3.5 mg daily (for BW up to 40 kg) or 1 tablet of 7 mg daily (for BW>40 kg). The adult range (5th-95th percentile) of predicted steady state PK parameters for 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Participants previously treated with placebo during the DB period received 1 teriflunomide tablet 3.5 mg (BW<=40 kg) or 7 mg teriflunomide (BW >40 kg) for first 8 weeks. After 8 weeks if predicted PK parameter was <= 95th percentile of adult range then participants received 7 mg teriflunomide (BW<=40 kg) and 14 mg teriflunomide (BW>40 kg) in the OL period for 96 weeks (i.e., up to Week 192). The adult range (5th-95th percentile) of predicted steady state PK parameters for 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL.
Participants previously treated with teriflunomide during DB period continued receiving teriflunomide in the OL period for additional 96 weeks (i.e., up to Week 192).
0
100
14
100
72
100
EG004
Extension Period/Teriflunomide
Participants who were not adults when they completed the 192-week OL period were offered an optional additional extension period to receive 1 teriflunomide tablet 14 mg daily (or every other day if BW <40 kg) until they became adults or until they were able to switch to the commercial product, whichever came first.
0
27
8
27
18
27
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Neutropenia
Blood and lymphatic system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG0031 events1 affected100 at risk
EG0040 events0 affected27 at risk
Bradycardia
Cardiac disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Cardiomyopathy
Cardiac disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Familial Mediterranean Fever
Congenital, familial and genetic disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Sudden Hearing Loss
Ear and labyrinth disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Diplopia
Eye disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Anal Fissure
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Anal Fistula
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Constipation
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Food Poisoning
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Pancreatic Disorder
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Pancreatitis Acute
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Asthenia
General disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Gait Disturbance
General disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Pyrexia
General disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Hepatic Function Abnormal
Hepatobiliary disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Acute Sinusitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Appendicitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Bronchitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Complicated Appendicitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Coronavirus Infection
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Encephalitis Viral
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Pneumonia
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Pulmonary Tuberculosis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Salpingo-Oophoritis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Tonsillitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0022 events1 affected52 at risk
EG003
Upper Respiratory Tract Infection
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Intentional Overdose
Injury, poisoning and procedural complications
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Joint Dislocation
Injury, poisoning and procedural complications
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Lumbar Vertebral Fracture
Injury, poisoning and procedural complications
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Peripheral Nerve Injury
Injury, poisoning and procedural complications
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Skin Laceration
Injury, poisoning and procedural complications
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Alanine Aminotransferase Increased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Blood Creatine Phosphokinase Increased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0012 events2 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Transaminases Increased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Dizziness
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Epilepsy
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0012 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Headache
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Multiple Sclerosis
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Multiple Sclerosis Pseudo Relapse
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Multiple Sclerosis Relapse
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Partial Seizures
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Syncope
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0013 events2 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Transient Ischaemic Attack
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Pregnancy
Pregnancy, puerperium and perinatal conditions
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Adjustment Disorder
Psychiatric disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Affective Disorder
Psychiatric disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Depression Suicidal
Psychiatric disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Somatic Symptom Disorder
Psychiatric disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Suicide Attempt
Psychiatric disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Renal Failure
Renal and urinary disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0010 events0 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Drug Eruption
Skin and subcutaneous tissue disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0013 events3 affected109 at risk
EG0020 events0 affected52 at risk
EG0036 events6 affected100 at risk
EG0040 events0 affected27 at risk
Lymphopenia
Blood and lymphatic system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0015 events3 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Palpitations
Cardiac disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0013 events3 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Sinus Bradycardia
Cardiac disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Sinus Tachycardia
Cardiac disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Ear Pain
Ear and labyrinth disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0013 events3 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Tinnitus
Ear and labyrinth disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0013 events3 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Autoimmune Thyroiditis
Endocrine disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Eye Pain
Eye disorders
MedDra 27.0
Systematic Assessment
EG0008 events4 affected57 at risk
EG0014 events4 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Vision Blurred
Eye disorders
MedDra 27.0
Systematic Assessment
EG0003 events2 affected57 at risk
EG0013 events2 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Visual Impairment
Eye disorders
MedDra 27.0
Systematic Assessment
EG0003 events2 affected57 at risk
EG0010 events0 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Abdominal Pain
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG00113 events11 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Abdominal Pain Upper
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0019 events6 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Aphthous Ulcer
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0012 events2 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Constipation
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0011 events1 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0004 events4 affected57 at risk
EG0019 events8 affected109 at risk
EG0028 events6 affected52 at risk
EG003
Gastrointestinal Disorder
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Mouth Ulceration
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0012 events2 affected109 at risk
EG0024 events2 affected52 at risk
EG003
Nausea
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0005 events4 affected57 at risk
EG00112 events10 affected109 at risk
EG0023 events3 affected52 at risk
EG003
Toothache
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0012 events2 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDra 27.0
Systematic Assessment
EG0005 events5 affected57 at risk
EG0017 events6 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Asthenia
General disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0012 events2 affected109 at risk
EG0023 events2 affected52 at risk
EG003
Fatigue
General disorders
MedDra 27.0
Systematic Assessment
EG0005 events3 affected57 at risk
EG0016 events4 affected109 at risk
EG0027 events4 affected52 at risk
EG003
Influenza Like Illness
General disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0013 events3 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Non-Cardiac Chest Pain
General disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0014 events4 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Pyrexia
General disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0018 events5 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Acute Sinusitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Bronchitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0015 events5 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Covid-19
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Cystitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0012 events1 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Gastroenteritis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0003 events3 affected57 at risk
EG0013 events3 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Influenza
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0004 events4 affected57 at risk
EG00116 events10 affected109 at risk
EG0026 events5 affected52 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0006 events5 affected57 at risk
EG00150 events28 affected109 at risk
EG00213 events8 affected52 at risk
EG003
Paronychia
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Pharyngitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0018 events7 affected109 at risk
EG0022 events1 affected52 at risk
EG003
Pulpitis Dental
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Respiratory Tract Infection
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0011 events1 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Respiratory Tract Infection Viral
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0017 events4 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Rhinitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0003 events2 affected57 at risk
EG0018 events4 affected109 at risk
EG0024 events2 affected52 at risk
EG003
Root Canal Infection
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Sinusitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0014 events4 affected109 at risk
EG0023 events2 affected52 at risk
EG003
Tinea Versicolour
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Tonsillitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0014 events4 affected109 at risk
EG0024 events2 affected52 at risk
EG003
Tracheitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Tracheobronchitis
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0010 events0 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Upper Respiratory Tract Infection
Infections and infestations
MedDra 27.0
Systematic Assessment
EG00023 events6 affected57 at risk
EG00166 events24 affected109 at risk
EG00232 events7 affected52 at risk
EG003
Urinary Tract Infection
Infections and infestations
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0013 events3 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Accidental Overdose
Injury, poisoning and procedural complications
MedDra 27.0
Systematic Assessment
EG0007 events4 affected57 at risk
EG0015 events5 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0014 events4 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDra 27.0
Systematic Assessment
EG0005 events4 affected57 at risk
EG0018 events6 affected109 at risk
EG0023 events2 affected52 at risk
EG003
Hip Fracture
Injury, poisoning and procedural complications
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Ligament Sprain
Injury, poisoning and procedural complications
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0011 events1 affected109 at risk
EG0023 events1 affected52 at risk
EG003
Thermal Burn
Injury, poisoning and procedural complications
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Alanine Aminotransferase Increased
Investigations
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0013 events2 affected109 at risk
EG0026 events6 affected52 at risk
EG003
Aspartate Aminotransferase Increased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Blood Albumin Increased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Blood Bilirubin Increased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Blood Creatine Phosphokinase Increased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0016 events4 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Blood Uric Acid Decreased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Electrocardiogram St-T Segment Abnormal
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Gamma-Glutamyltransferase Increased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Glomerular Filtration Rate Increased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Haematocrit Decreased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Haemoglobin Decreased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Monocyte Count Decreased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0012 events1 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Monocyte Percentage Increased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Neutrophil Count Decreased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0015 events3 affected109 at risk
EG0024 events1 affected52 at risk
EG003
Neutrophil Percentage Decreased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Neutrophil/Lymphocyte Ratio Decreased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Protein Urine Present
Investigations
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0015 events4 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Weight Decreased
Investigations
MedDra 27.0
Systematic Assessment
EG0003 events3 affected57 at risk
EG0017 events6 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Weight Increased
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0014 events3 affected109 at risk
EG0020 events0 affected52 at risk
EG003
White Blood Cell Count Decreased
Investigations
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0018 events5 affected109 at risk
EG0025 events2 affected52 at risk
EG003
White Blood Cells Urine Positive
Investigations
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Decreased Appetite
Metabolism and nutrition disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0013 events2 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Iron Deficiency
Metabolism and nutrition disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Vitamin D Deficiency
Metabolism and nutrition disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0014 events3 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDra 27.0
Systematic Assessment
EG0007 events3 affected57 at risk
EG0015 events5 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Back Pain
Musculoskeletal and connective tissue disorders
MedDra 27.0
Systematic Assessment
EG0003 events2 affected57 at risk
EG0016 events5 affected109 at risk
EG0023 events2 affected52 at risk
EG003
Muscle Spasms
Musculoskeletal and connective tissue disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0012 events2 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Muscular Weakness
Musculoskeletal and connective tissue disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0011 events1 affected109 at risk
EG0023 events3 affected52 at risk
EG003
Pain In Extremity
Musculoskeletal and connective tissue disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0013 events3 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Disturbance In Attention
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Dizziness
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0005 events4 affected57 at risk
EG0019 events9 affected109 at risk
EG00212 events6 affected52 at risk
EG003
Headache
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG00018 events13 affected57 at risk
EG00130 events18 affected109 at risk
EG00222 events7 affected52 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0005 events3 affected57 at risk
EG0017 events6 affected109 at risk
EG0024 events3 affected52 at risk
EG003
Paraesthesia
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0003 events2 affected57 at risk
EG00119 events11 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Presyncope
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0013 events3 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Syncope
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0011 events1 affected109 at risk
EG0023 events3 affected52 at risk
EG003
Tremor
Nervous system disorders
MedDra 27.0
Systematic Assessment
EG0003 events2 affected57 at risk
EG0011 events1 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Anxiety
Psychiatric disorders
MedDra 27.0
Systematic Assessment
EG0003 events3 affected57 at risk
EG0016 events4 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Depression
Psychiatric disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0012 events2 affected109 at risk
EG0024 events4 affected52 at risk
EG003
Insomnia
Psychiatric disorders
MedDra 27.0
Systematic Assessment
EG0003 events3 affected57 at risk
EG0011 events1 affected109 at risk
EG0023 events1 affected52 at risk
EG003
Mixed Anxiety And Depressive Disorder
Psychiatric disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Micturition Urgency
Renal and urinary disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0012 events2 affected109 at risk
EG0026 events5 affected52 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0012 events2 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDra 27.0
Systematic Assessment
EG0003 events3 affected57 at risk
EG0011 events1 affected109 at risk
EG0024 events1 affected52 at risk
EG003
Menstrual Disorder
Reproductive system and breast disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDra 27.0
Systematic Assessment
EG0003 events3 affected57 at risk
EG0016 events5 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0013 events3 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0014 events2 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Nasal Congestion
Respiratory, thoracic and mediastinal disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0013 events3 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Oropharyngeal Pain
Respiratory, thoracic and mediastinal disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0018 events7 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Respiratory Disorder
Respiratory, thoracic and mediastinal disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0023 events2 affected52 at risk
EG003
Rhinitis Allergic
Respiratory, thoracic and mediastinal disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0013 events3 affected109 at risk
EG0021 events1 affected52 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDra 27.0
Systematic Assessment
EG0004 events4 affected57 at risk
EG0015 events5 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDra 27.0
Systematic Assessment
EG0007 events7 affected57 at risk
EG00126 events24 affected109 at risk
EG00210 events9 affected52 at risk
EG003
Dry Skin
Skin and subcutaneous tissue disorders
MedDra 27.0
Systematic Assessment
EG0000 events0 affected57 at risk
EG0010 events0 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0011 events1 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDra 27.0
Systematic Assessment
EG0002 events2 affected57 at risk
EG0014 events4 affected109 at risk
EG0022 events2 affected52 at risk
EG003
Hypertension
Vascular disorders
MedDra 27.0
Systematic Assessment
EG0001 events1 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Orthostatic Hypotension
Vascular disorders
MedDra 27.0
Systematic Assessment
EG0003 events2 affected57 at risk
EG0010 events0 affected109 at risk
EG0020 events0 affected52 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00052
OG001100
Title
Denominators
Categories
Week 24
Title
Measurements
OG0000.750(0.609 to 0.846)
OG0010.820(0.730 to 0.883)
Week 48
Title
Measurements
OG0000.596(0.451 to 0.715)
OG0010.700(0.600 to 0.780)
Week 72
Title
Measurements
OG0000.519(0.377 to 0.644)
OG0010.630(0.528 to 0.716)
Week 96
Title
Measurements
OG0000.442(0.305 to 0.571)
OG0010.600(0.497 to 0.688)
Week 120
Title
Measurements
OG0000.404(0.271 to 0.533)
OG0010.570(0.467 to 0.660)
Week 144
Title
Measurements
OG0000.365(0.238 to 0.494)
OG0010.540(0.437 to 0.631)
Week 168
Title
Measurements
OG0000.365(0.238 to 0.494)
OG0010.518(0.416 to 0.611)
Week 192
Title
Measurements
OG0000.365(0.238 to 0.494)
OG0010.518(0.416 to 0.611)
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00052
OG001100
Title
Denominators
Categories
Title
Measurements
OG00011.087(6.586 to 18.662)
OG0015.664(3.417 to 9.389)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Relative risk ratio
0.511
2-Sided
95
0.343
0.762
Other
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00052
OG001100
Title
Denominators
Categories
Title
Measurements
OG0002.686(1.263 to 5.712)
OG0011.532(0.624 to 3.762)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Relative risk ratio
0.57
2-Sided
95
0.331
0.983
Other
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00052
OG00198
Title
Denominators
Categories
DB Period: Week 24
ParticipantsOG00040
ParticipantsOG00188
Title
Measurements
OG0003.0± 7.0
OG0010.5± 1.8
DB Period: Week 36
ParticipantsOG00019
ParticipantsOG00139
Title
Measurements
OG0004.6± 11.7
OG001
DB Period: Week 48
ParticipantsOG00021
ParticipantsOG00168
Title
Measurements
OG0000.5± 0.6
OG001
DB Period: Week 72
ParticipantsOG00016
ParticipantsOG00159
Title
Measurements
OG0001.2± 1.6
OG001
DB Period: Week 96
ParticipantsOG00014
ParticipantsOG00151
Title
Measurements
OG0000.9± 1.4
OG001
OL Period: Week 48
ParticipantsOG00051
ParticipantsOG00188
Title
Measurements
OG0003.0± 9.7
OG001
OL Period: Week 96
ParticipantsOG00037
ParticipantsOG00174
Title
Measurements
OG0002.7± 8.1
OG001
OL Period: Week 144
ParticipantsOG00020
ParticipantsOG00123
Title
Measurements
OG0004.7± 10.7
OG001
OL Period: Week 192
ParticipantsOG0005
ParticipantsOG0018
Title
Measurements
OG0000.4± 9.4
OG001
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00052
OG00198
Title
Denominators
Categories
DB Period: Week 24
ParticipantsOG00040
ParticipantsOG00188
Title
Measurements
OG0000.3± 1.3
OG0010.0± 0.7
DB Period: Week 36
ParticipantsOG00019
ParticipantsOG00139
Title
Measurements
OG0000.8± 1.8
OG001
DB Period: Week 48
ParticipantsOG00020
ParticipantsOG00168
Title
Measurements
OG0000.2± 0.4
OG001
DB Period: Week 72
ParticipantsOG00016
ParticipantsOG00158
Title
Measurements
OG0000.1± 0.7
OG001
DB Period: Week 96
ParticipantsOG00014
ParticipantsOG00150
Title
Measurements
OG0000.1± 0.6
OG001
OL Period: Week 48
ParticipantsOG00051
ParticipantsOG00186
Title
Measurements
OG0000.7± 1.9
OG001
OL Period: Week 96
ParticipantsOG00037
ParticipantsOG00173
Title
Measurements
OG0001.0± 2.0
OG001
OL Period: Week 144
ParticipantsOG00020
ParticipantsOG00122
Title
Measurements
OG0002.0± 3.0
OG001
OL Period: Week 192
ParticipantsOG0005
ParticipantsOG0018
Title
Measurements
OG0004.0± 5.8
OG001
Units
Counts
Participants
OG00052
OG001100
Title
Denominators
Categories
Title
Measurements
OG0001561
OG0011910
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Relative risk ratio
0.498
2-Sided
95
0.296
0.836
Other
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00052
OG001100
Title
Denominators
Categories
Week 24
Title
Measurements
OG00086.5
OG00186.0
Week 48
Title
Measurements
OG00032.7
OG00125.0
Week 72
Title
Measurements
OG00015.4
OG00117.0
Week 96
Title
Measurements
OG00015.4
OG00116.0
Week 144
Title
Measurements
OG00011.5
OG00114.0
Week 192
Title
Measurements
OG0007.7
OG0019.0
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00052
OG00197
Title
Denominators
Categories
DB Period: Week 24
ParticipantsOG00038
ParticipantsOG00183
Title
Measurements
OG000-0.3± 0.7
OG001-0.2± 0.7
DB Period: Week 36
ParticipantsOG00017
ParticipantsOG00139
Title
Measurements
OG000-0.7± 0.7
OG001
DB Period: Week 48
ParticipantsOG00020
ParticipantsOG00164
Title
Measurements
OG000-0.6± 1.1
OG001
DB Period: Week 72
ParticipantsOG00016
ParticipantsOG00153
Title
Measurements
OG000-0.9± 1.3
OG001
DB Period: Week 96
ParticipantsOG00013
ParticipantsOG00147
Title
Measurements
OG000-0.9± 1.3
OG001
OL Period: Week 48
ParticipantsOG00043
ParticipantsOG00173
Title
Measurements
OG000-1.4± 1.6
OG001
OL Period: Week 96
ParticipantsOG00033
ParticipantsOG00160
Title
Measurements
OG000-1.8± 1.9
OG001
OL Period: Week 144
ParticipantsOG00016
ParticipantsOG00117
Title
Measurements
OG000-3.1± 2.8
OG001
OL Period: Week 192
ParticipantsOG0004
ParticipantsOG0016
Title
Measurements
OG000-2.2± 1.2
OG001
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00051
OG00196
Title
Denominators
Categories
DB Period: Week 24
ParticipantsOG00040
ParticipantsOG00185
Title
Measurements
OG0005.1± 12.0
OG0014.6± 9.1
DB Period: Week 48
ParticipantsOG00020
ParticipantsOG00164
Title
Measurements
OG0007.3± 14.1
OG001
DB Period: Week 72
ParticipantsOG00017
ParticipantsOG00158
Title
Measurements
OG0006.4± 12.9
OG001
DB Period: Week 96
ParticipantsOG00014
ParticipantsOG00152
Title
Measurements
OG0008.8± 10.7
OG001
OL Period: Week 24
ParticipantsOG00051
ParticipantsOG00191
Title
Measurements
OG0006.3± 13.9
OG001
OL Period: Week 48
ParticipantsOG00044
ParticipantsOG00188
Title
Measurements
OG0006.7± 13.3
OG001
OL Period: Week 72
ParticipantsOG00041
ParticipantsOG00176
Title
Measurements
OG0008.0± 15.5
OG001
OL Period: Week 96
ParticipantsOG00036
ParticipantsOG00173
Title
Measurements
OG0007.6± 16.7
OG001
OL Period: Week 120
ParticipantsOG00022
ParticipantsOG00128
Title
Measurements
OG0003.7± 15.9
OG001
OL Period: Week 144
ParticipantsOG00018
ParticipantsOG00119
Title
Measurements
OG0006.6± 14.4
OG001
OL Period: Week 168
ParticipantsOG00013
ParticipantsOG00115
Title
Measurements
OG0003.5± 17.9
OG001
OL Period: Week 192
ParticipantsOG0001
ParticipantsOG0014
Title
Measurements
OG00012.0
OG001
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00051
OG00196
Title
Denominators
Categories
DB Period: Week 24
ParticipantsOG00040
ParticipantsOG00185
Title
Measurements
OG0003.8± 11.7
OG0013.6± 9.0
DB Period: Week 48
ParticipantsOG00020
ParticipantsOG00164
Title
Measurements
OG0006.3± 13.8
OG001
DB Period: Week 72
ParticipantsOG00017
ParticipantsOG00158
Title
Measurements
OG0005.1± 13.4
OG001
DB Period: Week 96
ParticipantsOG00014
ParticipantsOG00152
Title
Measurements
OG0007.1± 11.2
OG001
OL Period: Week 24
ParticipantsOG00051
ParticipantsOG00191
Title
Measurements
OG0004.8± 13.5
OG001
OL Period: Week 48
ParticipantsOG00044
ParticipantsOG00188
Title
Measurements
OG0005.5± 12.8
OG001
OL Period: Week 72
ParticipantsOG00041
ParticipantsOG00176
Title
Measurements
OG0006.4± 15.4
OG001
OL Period: Week 96
ParticipantsOG00036
ParticipantsOG00173
Title
Measurements
OG0006.3± 16.6
OG001
OL Period: Week 120
ParticipantsOG00022
ParticipantsOG00128
Title
Measurements
OG0003.7± 14.7
OG001
OL Period: Week 144
ParticipantsOG00018
ParticipantsOG00119
Title
Measurements
OG0004.8± 15.1
OG001
OL Period: Week 168
ParticipantsOG00013
ParticipantsOG00115
Title
Measurements
OG0002.7± 15.5
OG001
OL Period: Week 192
ParticipantsOG0001
ParticipantsOG0014
Title
Measurements
OG00012.0
OG001
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00031
OG00169
Title
Denominators
Categories
Baseline
ParticipantsOG00031
ParticipantsOG00169
Title
Measurements
OG00023.8± 7.2
OG00124.8± 6.4
Change at Week 96
ParticipantsOG0005
ParticipantsOG00135
Title
Measurements
OG000-0.8± 9.3
OG001
Change at Week 192
ParticipantsOG00016
ParticipantsOG00145
Title
Measurements
OG0001.0± 6.9
OG001
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00014
OG00129
Title
Denominators
Categories
Baseline
ParticipantsOG00014
ParticipantsOG00129
Title
Measurements
OG00043.4± 24.2
OG00147.1± 23.7
Change at Week 96
ParticipantsOG0003
ParticipantsOG00113
Title
Measurements
OG0008.4± 9.0
OG001
Change at Week 192
ParticipantsOG0008
ParticipantsOG00121
Title
Measurements
OG0006.3± 20.7
OG001
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00014
OG00128
Title
Denominators
Categories
Baseline
ParticipantsOG00014
ParticipantsOG00128
Title
Measurements
OG000113.8± 81.5
OG001115.0± 44.6
Change at Week 96
ParticipantsOG0003
ParticipantsOG00113
Title
Measurements
OG000-19.8± 33.7
OG001
Change at Week 192
ParticipantsOG0008
ParticipantsOG00121
Title
Measurements
OG000-37.0± 83.3
OG001
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00039
OG00182
Title
Denominators
Categories
Baseline
ParticipantsOG00039
ParticipantsOG00182
Title
Measurements
OG00026.1± 5.2
OG00125.9± 4.0
Change at Week 96
ParticipantsOG00010
ParticipantsOG00147
Title
Measurements
OG0000.6± 2.4
OG001
Change at Week 192
ParticipantsOG00026
ParticipantsOG00158
Title
Measurements
OG0000.1± 5.4
OG001
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG0001
OG0013
Title
Denominators
Categories
Baseline
ParticipantsOG0001
ParticipantsOG0013
Title
Measurements
OG00039.0
OG00134.3± 7.0
Change at Week 96
ParticipantsOG0001
ParticipantsOG0011
Title
Measurements
OG0005.0
OG001
Change at Week 192
ParticipantsOG0001
ParticipantsOG0011
Title
Measurements
OG0003.0
OG001
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG0002
OG0016
Title
Denominators
Categories
Baseline
ParticipantsOG0002
ParticipantsOG0016
Title
Measurements
OG00032.5± 3.5
OG00121.0± 6.0
Change at Week 96
ParticipantsOG0001
ParticipantsOG0012
Title
Measurements
OG000-3.0
OG001
Change at Week 192
ParticipantsOG0001
ParticipantsOG0012
Title
Measurements
OG0005.0
OG001
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG0002
OG0016
Title
Denominators
Categories
Baseline
ParticipantsOG0002
ParticipantsOG0016
Title
Measurements
OG00028.0± 1.4
OG00127.5± 9.2
Change at Week 96
ParticipantsOG0001
ParticipantsOG0012
Title
Measurements
OG0006.0
OG001
Change at Week 192
ParticipantsOG0001
ParticipantsOG0012
Title
Measurements
OG000-2.0
OG001
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG0002
OG0014
Title
Denominators
Categories
Baseline
ParticipantsOG0002
ParticipantsOG0014
Title
Measurements
OG0003.5± 4.9
OG00110.0± 1.4
Change at Week 96
ParticipantsOG0001
ParticipantsOG0012
Title
Measurements
OG0001.0
OG001
Change at Week 192
ParticipantsOG0001
ParticipantsOG0011
Title
Measurements
OG0000.0
OG001
OG001
Teriflunomide 7 mg
Participants with BW >40 kg received 1 teriflunomide tablet, 7 mg orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg).
OG002
Teriflunomide 14 mg
After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg).
Units
Counts
Participants
OG0000
OG00110
OG00266
Title
Denominators
Categories
Title
Measurements
OG00153.1± 25.3
OG00267.8± 41.7
OG001
Teriflunomide/ Teriflunomide
Participants received 1 teriflunomide tablet, 3.5 mg (in case of BW up to 40 kg) or 7 mg (in case of BW >40 kg) orally once daily for 8 weeks. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to 96 weeks: if predicted PK parameters <= 95th percentile of adult range after 7 mg once daily, then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if individual predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg). The adult range (5th - 95th percentile) of predicted steady state PK parameters for a 7 mg dose was defined as Cmax ranging from 8.03 to 49.10 mcg/mL and AUC0-24 ranging from 184 to 1160 mcg*h/mL. After completion of DB period, eligible participants entered in OL period and continued receiving teriflunomide at the same dose in the OL period for additional 96 weeks (i.e., up to Week 192).
Units
Counts
Participants
OG00052
OG001100
Title
Denominators
Categories
Title
Measurements
OG00095.86(0.6 to 176.0)
OG00196.00(1.0 to 183.4)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Hazard Ratio (HR)
0.693
2-Sided
95
0.37
1.296
Hazard ratio estimated using a Cox proportional-hazards model using treatment group, region, pubertal status, age, and number of relapses in the year prior to randomisation as covariates and with robust variance estimation.
Other
OG001
Placebo / Teriflunomide 7 mg
Participants previously treated with placebo during the DB period received teriflunomide 7 mg for 96 weeks in the OL period (i.e., up to Week 192).
OG002
Placebo / Teriflunomide 14 mg
Participants previously treated with placebo during the DB period received teriflunomide 14 mg for 96 weeks in OL period (i.e., up to Week 192).
OG003
Teriflunomide / Teriflunomide 3.5 mg
Participants previously treated with teriflunomide during the DB period received 1 teriflunomide tablet 3.5 mg orally once daily for first 8 weeks of OL period. After 8 weeks, based on individual predicted PK parameters, teriflunomide was administered in following manner up to Week 192: if predicted PK parameters <= 95th percentile of adult range then participants received 1 tablet of 7 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 14 mg teriflunomide daily (for BW >40 kg); or if predicted PK parameters >95th percentile of adult range then participants received 1 tablet of 3.5 mg teriflunomide daily (for BW up to 40 kg) or 1 tablet of 7 mg teriflunomide daily (for BW >40 kg).
OG004
Teriflunomide / Teriflunomide 7 mg
Participants previously treated with teriflunomide 7 mg during DB period continued receiving teriflunomide 7mg in the OL period for additional 96 weeks (i.e., up to Week 192).
OG005
Teriflunomide / Teriflunomide 14 mg
Participants previously treated with teriflunomide 14 mg during DB period continued receiving teriflunomide 14mg in the OL period for additional 96 weeks (i.e., up to Week 192).