E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Sclerosis |
Sclerosi multipla |
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E.1.1.1 | Medical condition in easily understood language |
Multiple Sclerosis |
Sclerosi multipla |
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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 | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | 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 |
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.
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Valutare l'effetto di teriflunomide rispetto a placebo sull’attività della malattia misurata come il tempo dalla prima recidiva clinica dopo la randomizzazione in bambini e adolescenti da 10 a 17 anni di età affetti da forme di sclerosi multipla recidivante |
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E.2.2 | Secondary objectives of the trial |
To assess the effect of teriflunomide in comparison to placebo on disease activity/progression measured by brain MRI and on cognitive function. To evaluate the safety and tolerability of teriflunomide in comparison to placebo. To evaluate the pharmacokinetics (PK) of teriflunomide.
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• Valutare l'effetto di teriflunomide in confronto al placebo sull’attività della malattia/progressione - misurata mediante risonanza magnetica (RM) cerebrale - e sulla funzione cognitiva • Valutare la sicurezza e la tollerabilità di teriflunomide in confronto al placebo • Valutare la farmacocinetica (PK) di teriflunomide |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Patients with relapsing multiple sclerosis are eligible. Patients should meet the criteria of 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 randomization or - at least two relapses (or attack) in the 24 months preceding randomization -=17 years of age and =10 years of age at randomization -Signed informed consent/assent obtained from patient and patient’s legal representative (parents or guardians) according to local regulations. |
• Pazienti con diagnosi di Sclerosi Multipla (SM) recidivante sulla base dei criteri di McDonald del 2010 e dei criteri del International Pediatric Multiple Sclerosis Study Group per i pazienti pediatrici MS e che hanno: - almeno una recidiva (o attacco) nei 12 mesi precedenti la randomizzazione, o - almeno due recidive (o attacchi) nei 24 mesi precedenti la randomizzazione • =17 anni di età e = 10 anni di età al momento della randomizzazione • Consenso informato / assenso firmato, ottenuto dal paziente e dai rappresentanti legali del paziente (genitori o tutore) in base alla normativa locale |
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E.4 | Principal exclusion criteria |
• 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 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). |
• Punteggio EDSS> 5.5 alla visita di screening o di randomizzazione • Recidiva nei 30 giorni precedenti la randomizzazione • Trattato con - glatiramer acetato, interferoni, o dimetil-fumarato entro 1 mese prima della randomizzazione - fingolimod, o immunoglobuline somministrate per via endovenosa entro 3 mesi prima della randomizzazione - natalizumab, altri immunosoppressori o agenti immunomodulanti come la ciclofosfamide, azatioprina, ciclosporina, metotrexate, micofenolato, entro 6 mesi prima della randomizzazione - cladribina o mitoxantrone nei 2 anni precedenti la randomizzazione • Trattato con alemtuzumab in qualsiasi momento • Storia di infezione da HIV • Controindicazione per la RM • Donne in gravidanza o allattamento o che abbiano intenzione di diventare gravide durante lo studio • Pazienti di sesso femminile in età fertile che non usano metodi contraccettivi altamente efficaci (è richiesta sia la contraccezione maschile che quella femminile). |
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E.5 End points |
E.5.1 | Primary end point(s) |
1-Time to first clinical relapse after randomization |
1- Tempo alla prima recidiva clinica dopo la randomizzazione |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Over 96 weeks |
Per 96 settimane |
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E.5.2 | Secondary end point(s) |
2 - Proportion of relapse free patients 3 - Number of new/newly enlarged T2 lesions 4 - Number of T1 Gd-enhancing T1 lesions 5 - Change in volume of T2 lesions - Change in volume of T1 hypointense lesions 6 - Number of new T1 hypointense lesions 7 - Proportion of patients free of new or enlarged MRI T2-lesions 8 - Brain atrophy 9 - Change in performance on symbol digit modalities test (SDMT) and Cognitive Battery Test 10 - Safety, as assessed by clinical, laboratory, ECG, and vital signs events 11 - Teriflunomide pharmacokinetics (PK)</ |
2 – Percentuale di pazienti liberi da recidiva 3 – Numero di lesioni T2 Nuove/accresciute 4 – Numero di lesioni T1 captanti Gadolinio 5 - Variazione del volume delle lesioni T2 - Variazione del volume delle lesioni T1 ipointense 6 - Numero di nuove lesioni T1 ipointense 7 - Percentuale di pazienti liberi da lesioni T2 nuove o accresciute alla RM 8 - Atrofia cerebrale 9 – Variazioni nelle prestazioni al Symbol Digit Modalities Test (SDMT) e su una batteria di test cognitivi 10 – Sicurezza valutata attraverso eventi clinici e di laboratorio, ECG e segni vitali 11 – Farmacocinetica di Teriflunomide (PK) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2: at 24, 48, 72 and 96 weeks 3, 4, 5, 6, 8 and 10: over 96 weeks 7: at 48 weeks and 96 weeks 9: at randomization, then every 24 weeks (SDMT only) and at 96 weeks 11: at Weeks 2, 3, 4, 8, 12, 24, 36 and EOT |
- 2: alle settimane 24, 48, 72 e 96 - 3, 4, 5, 6, 8 e 10: per 96 settimane - 7: alle settimane 48 e 96 - 9: alla randomizzazione, successivamente ogni 24 settimane (solo SDMT) e alla settimana 96 11: alle settimane 2, 3, 4, 8, 12, 24, 36 ed alla visita di fine trattamento (EOT) |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
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 | No |
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 |
Opzione di passare a teriflunomide in aperto per pazienti con recidiva dopo PK fase run-in |
Option to go in an open label teriflunomide arm for patients having a relapse after PK run-in phase |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 | Information not present in EudraCT |
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 |
Australia |
Bosnia and Herzegovina |
Canada |
China |
Israel |
Lebanon |
North Macedonia |
Morocco |
Russian Federation |
Serbia |
Tunisia |
Turkey |
United States |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 19 |