E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | Relapsing-remitting multiple sclerosis with paediatric onset | Sclerosi multipla ad esordio pediatrico con forma recidivante-remittente (RR) | |
E.1.1.1 | Medical condition in easily understood language | Multiple sclerosis in children and adolescents aged up to 17 years wth relapsing-remitting course | Sclerosi multipla ad insorgenza in età inferiore ai 17 anni con forma recidivante-remittente (RR) | |
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 | |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial | The main objective of the study is to demonstrate the equivalence of two of injectable drugs (IFN beta 1a 30-mcg im weekly and GA 40 mg s.c. e.o.d.) currently used for the treatment of POMS or the superiority of one of them on MRI and clinical effectiveness outcomes. | Confrontare la sicurezza (frequenza e tipo di eventi avversi) e l'efficacia (attraverso misure di risonanza magnetica) tra l'IFN-beta 1a settimanale i.m. e GA in POMS con forma recidivante-remittente (RR). | |
E.2.2 | Secondary objectives of the trial | Secondary objectives are to compare safety and cost-effectiveness of the two drugs. | Confrontare l'efficacia dell’IFN-beta 1a e GA sul tasso annuale di recidive (ARR), su outcome cognitivi, comportamentali e riportati dal paziente (PRO). | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria | •Diagnosis of POMS [23,24] •Male and female children and adolescents aged between 10 to 17 years included at the time of informed consent (i.e. have not yet had their 18th birthday at randomization); •Treatment naïve; •Signed and dated informed consent from parents/legal representative; •Relapsing remitting course; •At least one MS relapse during the previous year; •EDSS score of 0 to 5.5, inclusive •Subjects of childbearing potential who are sexually active must be willing to practice effective contraception during the study. | •Diagnosi di Sclerosi Multipla Pediatrica (secondo i criteri di Krupp e colleghi 2013); •Bambini e adolescenti di età compresa tra 10 e 17 anni inclusi al momento della firma del consenso informato (ovvero che non hanno ancora raggiunto il loro diciottesimo compleanno alla randomizzazione) •Naïve al trattamento; •Consenso informato datato e firmato dai genitori/rappresentante legale; •Decorso di malattia recidivante-remittente; •Presenza di almeno una ricaduta nell’anno precedente; •Punteggio di disabilità (EDSS score) compreso tra 0 e 5.5 incluso; •I soggetti in età fertile che sono sessualmente attivi devono essere disposti a praticare contraccettivi efficaci durante lo studio. | |
E.4 | Principal exclusion criteria | •Patients with progressive MS; •Patients with an active, chronic disease of the immune system other than MS; •Patients meeting the definition of Acute Disseminated Encephalomyelitis (ADEM); •Patients with thyroid dysfunction; •Patients with severe renal insufficiency | •Pazienti con Sclerosi Multipla progressiva; •Pazienti con una malattia cronica attiva del sistema immunitario diversa dalla SM; •Pazienti che soddisfano la definizione di Encefalomielite acuta disseminata (ADEM); •Pazienti con disfunzione tiroidea; •Pazienti con insufficienza renale grave. | |
E.5 End points |
E.5.1 | Primary end point(s) | Proportion of subjects free of new or newly enlarging T2 hyperintense on brain MRI scans at 96 weeks. | Proporzione di soggetti liberi da lesioni T2 iperintense nuove o in allargamento nell’ MRI celebrale a 96 settimane | |
E.5.1.1 | Timepoint(s) of evaluation of this end point | |
E.5.2 | Secondary end point(s) | Efficacy endpoints: •Annualized relapse rate (ARR) at Weeks 48 and 96; •Proportion of subjects free of relapse up to Week 96; •Time to first relapse; •Time to disability progression defined as 1-point increase of the Expanded Disability Status Scale (EDSS) score confirmed at Week 24; •Number of new or newly enlarging T2 hyperintense lesions on brain MRI scans at Weeks 48 and 96; •Number of MRI T1 Gd-enhancing lesions on brain MRI scans at Weeks 48 and 96; •Change of Symbol Digit Modality test (SDMT) at Weeks 48 and 96; •Change of Fatigue (FS) score at Weeks 48 and 96; •Change of QOL (ped QOL) evaluated through Patient Reported Outcomes (PROs) at Weeks 48 and 96; •Cost-efficacy analyses. An estimate of the cost-effectiveness of the therapeutic regimens under examination. Safety endpoint: •Frequency and type of Adverse Events (AEs) during all the study | Endpoint di efficacia: •Frequenza Annuale di recidive (ARR) a 48 e 96 settimane; •Proporzione di soggetti liberi da recidive fino alla 96 settimana; •comparsa della prima recidiva; •comparsa di progressione della disabilità definita come aumento di 1 punto della Expanded Disability Status Scale (EDSS) confermato alla settimana 24; •Numero di lesioni T2 iperintense nuove o in allargamento nell’ MRI celebrale alla settimana 48 e 96; •Numero di lesioni T1 Gd-enhancing alla MRI celebrale alla settimana 48 e 96; •Variazioni del Symbol Digit Modality Test (SDMT) alla settimana 48 e 96; •Variazione del Fatigue (FS) score alla settimana 48 e 96; •Variazione del QOL (ped QOL) valutato attraverso il Patient Reported Outcomes (PROs) alla settimana 48 e 96; •Analisi costo-efficacia. Una stima del costo-efficacia del regime terapeutico sotto esame. Endpoint di Sicurezza: Frequenza e tipo di Evento Avverso (AEs) durante tutto lo studio | |
E.5.2.1 | Timepoint(s) of evaluation of this end point | |
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 | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
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 | 19 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | Study end is defined as the database lock | La fine dello studio è sancita dalla chiusura del database. | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |