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

NCT ID: NCT02201108

Last Updated: 2025-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 166 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-16
• Study Completion Date: 2024-07-29

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

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Matching placebo tablets

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pharmaceutical form:tablet, Route of administration: oral

Teriflunomide

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

Group Type: EXPERIMENTAL

Teriflunomide

Intervention Type: DRUG

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

Interventions

Teriflunomide

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

Intervention Type: DRUG

Placebo

Pharmaceutical form:tablet, Route of administration: oral

Intervention Type: DRUG

Other Intervention Names

AUBAGIO, HMR1726

Eligibility Criteria

Inclusion Criteria

• 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.

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

North Central Neurology Associates, PC Site Number : 840003

Cullman, Alabama, United States

Axiom Clinical Research of Florida Site Number : 840012

Tampa, Florida, United States

Massachusetts General Hospital Site Number : 840002

Boston, Massachusetts, United States

Raleigh Neurology Associates Site Number : 840004

Raleigh, North Carolina, United States

Investigational Site Number : 056002

Ghent, , Belgium

Investigational Site Number : 056001

Leuven, , Belgium

Investigational Site Number : 100001

Sofia, , Bulgaria

Investigational Site Number : 124001

Calgary, Alberta, Canada

Investigational Site Number : 156001

Beijing, , China

Investigational Site Number : 156002

Beijing, , China

Investigational Site Number : 156010

Beijing, , China

Investigational Site Number : 156006

Changchun, , China

Investigational Site Number : 156007

Changsha, , China

Investigational Site Number : 156008

Chengdu, , China

Investigational Site Number : 156005

Chongqing, , China

Investigational Site Number : 156012

Guangzhou, , China

Investigational Site Number : 156003

Shanghai, , China

Investigational Site Number : 156004

Shanghai, , China

Investigational Site Number : 156011

Shijiazhuang, , China

Investigational Site Number : 156009

Taiyuan, , China

Investigational Site Number : 233001

Tallinn, , Estonia

Investigational Site Number : 250001

Le Kremlin-Bicêtre, , France

Investigational Site Number : 250002

Lyon, , France

Investigational Site Number : 250003

Rennes, , France

Investigational Site Number : 250005

Toulouse, , France

Investigational Site Number : 300002

Athens, , Greece

Investigational Site Number : 300001

Thessaloniki, , Greece

Investigational Site Number : 376001

Jerusalem, , Israel

Investigational Site Number : 376003

Tel Litwinsky, , Israel

Investigational Site Number : 422001

Beirut, , Lebanon

Investigational Site Number : 440001

Kaunas, , Lithuania

Investigational Site Number : 504004

Fes, , Morocco

Investigational Site Number : 504005

Marrakesh, , Morocco

Investigational Site Number : 528001

Rotterdam, , Netherlands

Investigational Site Number : 807002

Shtip, , North Macedonia

Investigational Site Number : 807001

Skopje, , North Macedonia

Investigational Site Number : 620001

Coimbra, , Portugal

Investigational Site Number : 643001

Moscow, , Russia

Investigational Site Number : 643003

Nizhny Novgorod, , Russia

Investigational Site Number : 643004

Novosibirsk, , Russia

Investigational Site Number : 643005

Saint Petersburg, , Russia

Investigational Site Number : 643002

Saint Petersburg, , Russia

Investigational Site Number : 688002

Belgrade, , Serbia

Investigational Site Number : 724002

Murcia, , Spain

Investigational Site Number : 788001

Manouba, , Tunisia

Investigational Site Number : 788002

Sfax, , Tunisia

Investigational Site Number : 788004

Sfax, , Tunisia

Investigational Site Number : 792002

Ankara, , Turkey (Türkiye)

Investigational Site Number : 792001

Ankara, , Turkey (Türkiye)

Investigational Site Number : 792006

Istanbul, , Turkey (Türkiye)

Investigational Site Number : 792003

Istanbul, , Turkey (Türkiye)

Investigational Site Number : 792008

Izmir, , Turkey (Türkiye)

Investigational Site Number : 792007

Izmir, , Turkey (Türkiye)

Investigational Site Number : 804001

Kharkiv, , Ukraine

Investigational Site Number : 804002

Kharkiv, , Ukraine

Investigational Site Number : 826001

London, London, City of, United Kingdom

Investigational Site Number : 826003

Birmingham, , United Kingdom

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

References

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.

Reference Type: DERIVED

PMID: 38619037 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36632983 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34800398 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1124-0983

Identifier Type: REGISTRY

Identifier Source: secondary_id

2011-005249-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC11759

Identifier Type: -

Identifier Source: org_study_id