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

NCT02201108 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC11759U1111-1124-09832011-005249-12
• Study Type: interventional
• Target: 166
• Locations: 20 countries
• Sites: 50

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 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 (21)

• Probability of Participants Who Were Clinical Relapse Free at Weeks 24, 48, 72, 96, 120, 144, 168 and 192

  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

  Baseline up to Week 192

• Brain Magnetic Resonance Imaging Assessment: Number of T1 Gadolinium (Gd)-Enhancing T1 Lesions Per MRI Scan

  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

  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

  Baseline, DB period: Weeks 24, 36, 48, 72 and 96; OL period: Weeks 48, 96, 144 and 192

Study Arms (2)

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

Teriflunomide DRUG

Pharmaceutical form:film-coated tablet, Route of administration: oral

Also known as: AUBAGIO, HMR1726

Teriflunomide

Placebo DRUG

Pharmaceutical form:tablet, Route of administration: oral

Placebo

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (57)

North Central Neurology Associates, PC Site Number : 840003

Cullman, Alabama, 35058, United States

Location

Axiom Clinical Research of Florida Site Number : 840012

Tampa, Florida, 33609-4052, United States

Location

Massachusetts General Hospital Site Number : 840002

Boston, Massachusetts, 02114, United States

Location

Raleigh Neurology Associates Site Number : 840004

Raleigh, North Carolina, 27607, United States

Location

Investigational Site Number : 056002

Ghent, 9000, Belgium

Location

Investigational Site Number : 056001

Leuven, 3000, Belgium

Location

Investigational Site Number : 100001

Sofia, 1113, Bulgaria

Location

Investigational Site Number : 124001

Calgary, Alberta, T3B 6A8, Canada

Location

Investigational Site Number : 156001

Beijing, 100034, China

Location

Investigational Site Number : 156002

Beijing, 100045, China

Location

Investigational Site Number : 156010

Beijing, 100730, China

Location

Investigational Site Number : 156006

Changchun, 130021, China

Location

Investigational Site Number : 156007

Changsha, 410011, China

Location

Investigational Site Number : 156008

Chengdu, 610041, China

Location

Investigational Site Number : 156005

Chongqing, 400014, China

Location

Investigational Site Number : 156012

Guangzhou, 510630, China

Location

Investigational Site Number : 156003

Shanghai, 200092, China

Location

Investigational Site Number : 156004

Shanghai, 201102, China

Location

Investigational Site Number : 156011

Shijiazhuang, 050000, China

Location

Investigational Site Number : 156009

Taiyuan, 030001, China

Location

Investigational Site Number : 233001

Tallinn, 10617, Estonia

Location

Investigational Site Number : 250001

Le Kremlin-Bicêtre, 94270, France

Location

Investigational Site Number : 250002

Lyon, 69394, France

Location

Investigational Site Number : 250003

Rennes, 35033, France

Location

Investigational Site Number : 250005

Toulouse, 31059, France

Location

Investigational Site Number : 300002

Athens, 115 27, Greece

Location

Investigational Site Number : 300001

Thessaloniki, 54642, Greece

Location

Investigational Site Number : 376001

Jerusalem, 91120, Israel

Location

Investigational Site Number : 376003

Tel Litwinsky, 52621, Israel

Location

Investigational Site Number : 422001

Beirut, 11-0236, Lebanon

Location

Investigational Site Number : 440001

Kaunas, 50161, Lithuania

Location

Investigational Site Number : 504004

Fes, Morocco

Location

Investigational Site Number : 504005

Marrakesh, 40000, Morocco

Location

Investigational Site Number : 528001

Rotterdam, 3015 CN, Netherlands

Location

Investigational Site Number : 807002

Shtip, 2000, North Macedonia

Location

Investigational Site Number : 807001

Skopje, 1000, North Macedonia

Location

Investigational Site Number : 620001

Coimbra, 3000-075, Portugal

Location

Investigational Site Number : 643001

Moscow, 127566, Russia

Location

Investigational Site Number : 643003

Nizhny Novgorod, 603155, Russia

Location

Investigational Site Number : 643004

Novosibirsk, 630087, Russia

Location

Investigational Site Number : 643005

Saint Petersburg, 197022, Russia

Location

Investigational Site Number : 643002

Saint Petersburg, 197110, Russia

Location

Investigational Site Number : 688002

Belgrade, 11000, Serbia

Location

Investigational Site Number : 724002

Murcia, 30120, Spain

Location

Investigational Site Number : 788001

Manouba, 2020, Tunisia

Location

Investigational Site Number : 788002

Sfax, 3029, Tunisia

Location

Investigational Site Number : 788004

Sfax, 3029, Tunisia

Location

Investigational Site Number : 792002

Ankara, 06100, Turkey (Türkiye)

Location

Investigational Site Number : 792001

Ankara, 06500, Turkey (Türkiye)

Location

Investigational Site Number : 792006

Istanbul, 34390, Turkey (Türkiye)

Location

Investigational Site Number : 792003

Istanbul, 34688, Turkey (Türkiye)

Location

Investigational Site Number : 792008

Izmir, 35210, Turkey (Türkiye)

Location

Investigational Site Number : 792007

Izmir, Turkey (Türkiye)

Location

Investigational Site Number : 804001

Kharkiv, 61068, Ukraine

Location

Investigational Site Number : 804002

Kharkiv, 61068, Ukraine

Location

Investigational Site Number : 826001

London, London, City of, SE1 7EH, United Kingdom

Location

Investigational Site Number : 826003

Birmingham, B4 6NH, United Kingdom

Location

Related Publications (3)

• Chitnis T, Banwell B, Kappos L, Arnold DL, Gucuyener K, Deiva K, Saubadu S, Hu W, Benamor M, Le-Halpere A, Truffinet P, Tardieu M. Teriflunomide in pediatric patients with relapsing multiple sclerosis: Open-label extension of TERIKIDS. Mult Scler. 2024 Jun;30(7):833-842. doi: 10.1177/13524585241242050. Epub 2024 Apr 15.

  PMID: 38619037 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.

  PMID: 36632983 DERIVED

• 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.

  PMID: 34800398 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

teriflunomide

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Genzyme, a Sanofi Company

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2014
• First Posted: July 25, 2014
• Study Start: July 16, 2014
• Primary Completion: October 25, 2019
• Study Completion: July 29, 2024
• Last Updated: February 6, 2025
• Results First Posted: November 30, 2020

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

ES (1); UA (2); LI (1); IL (2); US (4); CA (1); NL (1); BU (1); PT (1); RU (5); SE (1); GR (2); TU (3); CN (12); LE (1); FR (4); MO (2); NO (2); GB (2); BE (2)