E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-remitting Multiple Sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
Chronic inflammatory disease attacking the CNS |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063399 |
E.1.2 | Term | Relapsing-remitting multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to demonstrate that ponesimod is not less effective than fingolimod in reducing relapses in pediatric participants with relapsing remitting multiple sclerosis (RRMS) if treatment is taken as directed through Week 108 |
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E.2.2 | Secondary objectives of the trial |
● To assess whether ponesimod and fingolimod independently achieve an ARR of <0.3 ● To assess the effect of ponesimod on MS disability accumulation and magnetic resonance imaging (MRI) lesion accrual in comparison with fingolimod in pediatric participants with RRMS ●To evaluate the safety, tolerability, and pharmacodynamics (PD) of ponesimod in comparison with fingolimod in pediatric participants with RRMS ●To evaluate the pharmacokinetics (PK) of ponesimod in pediatric participants with RRMS ●To study the PK/PD relationship for key efficacy and safety outcomes in pediatric participants with RRMS treated with ponesimod |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Open-Label PK sub-study will be conducted in parallel to the main study Objective: To determine if a maintenance dose of < 20 mg ponesimod in pediatric population with body weight <= 40 kg results in PK exposure and PD effects comparable to those achieved in adult participants with RMS |
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E.3 | Principal inclusion criteria |
- A diagnosis of relapsing-remitting multiple sclerosis (RRMS) as defined by the 2017 revisions of the McDonald criteria. Central review of the diagnosis of pediatric multiple sclerosis (MS) will be required for all participants prior to Visit 3 (Day 1, randomization). - Expanded Disability Status Scale (EDSS) score between 0 and 5.5 (inclusive) at Visit 1 (Screening) and Visit 2 (Baseline). - At least 1 MS relapse during the previous year or 2 MS relapses in the previous 2 years or evidence of Gd+ lesions on MRI 6 months prior to Visit 3 (Day 1, Randomization), including MRI at Visit 1 (Screening). - Must be otherwise healthy per investigator clinical judgement on the basis of physical examination, medical history, vital signs, laboratory tests, and electrocardiogram (ECGs) at Visit 1 (Screening). Any documented abnormalities must be consistent with pediatric MS. This determination must be recorded in participant’s source documents and initiated by Principal investigator (PI). - Participants with body weight or body surface area between 5th and 95th percentile for age and sex. Overweight participants greater than 95th percentile and underweight participants less than 5th percentile may participate following medical clearance, but the minimum body weight required for study participation is 20 kg.
Refer protocol for all inclusion criteria.
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E.4 | Principal exclusion criteria |
- Presenting with a diagnosis of MS with progressive course from onset (that is, primary progressive MS or progressive relapsing MS).
- Widespread and symmetric white matter alterations in the baseline MRI suggestive of other demyelinating disorders (example, metabolic disorders, mitochondrial disorders).
- Tested positive for aquaporin 4 (AQP4) or anti-myelin oligodendrocyte glycoprotein (MOG) antibodies at Visit 1 (Screening).
- Pregnant (defined as the state of a female after conception and until the termination of gestation, confirmed by a positive Human Chorionic Gonadotropin laboratory test), or breastfeeding, or planning to become pregnant while enrolled in this study.
- Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
Refer protocol for all exclusion criteria.
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E.5 End points |
E.5.1 | Primary end point(s) |
Annualized relapse rate (ARR), defined as the number of confirmed relapses per participant-year through Week 108 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From Randomization to Week 108 |
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E.5.2 | Secondary end point(s) |
1. ARR 2. Disability: - Time to 12- and 24-week confirmed disability accumulation as measured by Expanded Disability Status Scale (EDSS) score 3. MRI: - Annualized rate of new/newly enlarging T2 lesions - Cumulative number of new/newly enlarging T2 lesions from baseline to Week 108 - Proportion of participants free of new/newly enlarging T2 lesions at End of Treatment (EOT) and by visit (ie, Week 24, 48 and 108) 4. Safety / tolerability - Adverse events (AEs), including AEs of special interest (AESI) - Electrocardiogram (ECG) parameters, including heart rate (HR), intervals for PR, QRS, QT, and QTcF - Pulmonary function test (PFT), including forced expiratory volume in 1 second (FEV1), and forced vital capacity (FVC) - Blood pressure - Laboratory values, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin - Change in body weight/height from Baseline to End of Study (EOS) - Suicidality assessment using the Columbia-Suicide Severity Rating Scale (C-SSRS) 5. Pharmacodynamics - Peripheral blood lymphocyte counts on Day 1 and at Weeks 4 and 12 6. Pharmacokinetics - PK sub-study: Population PK parameters (AUC, Cmax, Tmax, t1/2) - Main study: Population PK parameters, such as AUC and Cmax (if data allow) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At timepoints as specified within the protocol |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker evaluation, Tolerability, analysis of MRI parameters, cognitive function, fatigue and Health-related quality of life |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United Kingdom |
Belgium |
Bulgaria |
Czechia |
France |
Germany |
Hungary |
Italy |
Poland |
Portugal |
Spain |
Sweden |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |