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

• ClinicalTrials.gov Identifier: NCT02201108
• Recruitment Status: Active, not recruiting
• First Posted: July 25, 2014
• Last Update Posted: November 29, 2019
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Tracking Information

• First Submitted Date: July 17, 2014
• First Posted Date: July 25, 2014
• Last Update Posted Date: November 29, 2019
• Actual Study Start Date: July 16, 2014
• Actual Primary Completion Date: October 30, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 24, 2014): Time to first clinical relapse after randomization [ Time Frame: over 96 weeks ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT02201108 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: October 26, 2018)

• Proportion of relapse free participants [ Time Frame: at 24, 48, 72 and 96 weeks ]
• Number of of new/newly enlarged T2 lesions [ Time Frame: over 96 weeks ]
• Number of T1 Gd-enhancing T1 lesions [ Time Frame: over 96 weeks ]
• Change in volume of T2 lesions [ Time Frame: over 96 weeks ]
• Change in volume of T1 hypointense lesions [ Time Frame: over 96 weeks ]
• Number of new T1 hypointense lesions [ Time Frame: over 96 weeks ]
• Proportion of participants free of new or enlarged MRI T2-lesions [ Time Frame: at 48 weeks and 96 weeks ]
• Brain atrophy [ Time Frame: over 96 weeks ]
• Change in performance on symbol digit modalities test (SDMT) and Cognitive Battery Test [ Time Frame: at randomization, then every 24 weeks (SDMT only) and at 96 weeks ]
• Safety, as assessed by clinical, laboratory, ECG, and vital signs events [ Time Frame: over 96 weeks ]
• Assessment of teriflunomide pharmacokinetics (PK) parameter: (Ctrough) lowest concentration of drug in the blood measured after dosing [ Time Frame: at Weeks 2, 3, 4, 8, 12, 24, 36 and 96 ]
• Assessment of teriflunomide PK parameter: (Cmax) maximum plasma drug concentration [ Time Frame: at Weeks 2, 3, 4, 8, 12, 24, 36 and 96 ]
• Assessment of teriflunomide PK parameter: (AUC0-24) area under the plasma concentration-time curve from time zero to 24 hours [ Time Frame: at Weeks 2, 3, 4, 8, 12, 24, 36 and 96 ]

Original Secondary Outcome Measures (submitted: July 24, 2014)

• Proportion of relapse free patients [ Time Frame: at 24, 48, 72 and 96 weeks ]
• Number of of new/newly enlarged T2 lesions [ Time Frame: at 24, 48, 72 and 96 weeks ]
• Number of T1 Gd-enhancing T1 lesions [ Time Frame: over 96 weeks ]
• Change in volume of T2 lesions [ Time Frame: over 96 weeks ]
• Change in volume of T1 hypointense lesions [ Time Frame: over 96 weeks ]
• Number of new T1 hypointense lesions [ Time Frame: over 96 weeks ]
• Proportion of patients free of new or enlarged MRI T2-lesions [ Time Frame: at 48 weeks and 96 weeks ]
• Brain atrophy [ Time Frame: over 96 weeks ]
• Change in performance on symbol digit modalities test (SDMT) and Cognitive Battery Test [ Time Frame: at randomization, then every 24 weeks (SDMT only) and at 96 weeks ]
• Safety, as assessed by clinical, laboratory, ECG, and vital signs events [ Time Frame: over 96 weeks ]
• Assessment of PK parameter - lowest concentration of drug in the blood measured after dosing (Ctrough) [ Time Frame: at Weeks 2, 3, 4, 8, 12, 24, 36 and 96 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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.

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 includes a screening period up to 4 weeks, a double-blind treatment period of up to 96 weeks, an open-label period including 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 will be a follow-up period of 4 weeks for participants discontinuing treatment.

Within the 96 weeks double-blind treatment period, the first 4 weeks are pharmacokinetic (PK) run-in phase in which PK samples (blood samples) will be collected from participants and then 4 weeks of analysis (no samples drawn). The PK run-in phase (total 8 weeks) is intended to provide individual PK parameters to allow the dose adjustment to the 14 mg adult-equivalent dose for the rest of the study.

Participants experiencing a relapse after the PK run-in phase (8 weeks) and if confirmed by the Relapse Adjudication Panel (RAP) and patients fulfilling MRI criteria (high number of new lesions at week 36, 48 or 72 compared to previous images) will have the option to continue in an open label teriflunomide treatment arm up to 192 weeks from randomization.

An optional additional extension period is available for young participants with teriflunomide until the participants are 18 years old and/or able to switch to commercial product, whichever comes first.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Multiple Sclerosis

Intervention

• Drug: Teriflunomide
  Pharmaceutical form:film-coated tablet Route of administration: oral
  Other Name: AUBAGIO, HMR1726
• Drug: Placebo
  Pharmaceutical form:tablet Route of administration: oral

Study Arms

• Placebo Comparator: Placebo
  Matching placebo tablets
  Intervention: Drug: Placebo
• Experimental: Teriflunomide
  Teriflunomide oral tablet, three dosages (3.5, 7 or 14 mg) to reach 14 mg adult equivalent
  Intervention: Drug: Teriflunomide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: July 24, 2014): 165
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 29, 2021
• Actual Primary Completion Date: October 30, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria :

• Patients with relapsing multiple sclerosis are eligible. Patients should meet the criteria of multiple sclerosis (MS) based on McDonald criteria 2010 and International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric MS, version of 2012 (5) and have:
• 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.
• <18 years of age and ≥10 years of age at randomization. Specific for the Russian Federation from 18 December 2014 to 26 July 2016, ≤17 years of age and ≥13 years of age at randomization
• Signed informed consent/assent obtained from patient and patient's legal representative (parents or guardians) according to local regulations.

Exclusion criteria:

• Expanded disability status scale (EDSS) score > 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 HIV infection.
• Contraindication for magnetic resonance imaging (MRI).
• Pregnant or breast-feeding females or those who plan to become pregnant during the study.
• Female patients of child-bearing potential not using highly effective contraceptive method (contraception in both female and male is required).

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 10 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Bulgaria, Canada, China, Estonia, France, Greece, Israel, Lebanon, Lithuania, Morocco, Netherlands, North Macedonia, Portugal, Russian Federation, Serbia, Slovenia, Spain, Tunisia, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Australia, Macedonia, The Former Yugoslav Republic of, Poland

Administrative Information

• NCT Number: NCT02201108
• Other Study ID Numbers: EFC11759; 2011-005249-12 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
• Study Sponsor: Genzyme, a Sanofi Company
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: November 2019