E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsing-remitting multiple sclerosis (RRMS) |
sclerosi multipla recidivante remittente |
|
E.1.1.1 | Medical condition in easily understood language |
multiple sclerosis |
sclerosi multipla |
|
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 of this study is to evaluate the efficacy of natalizumab extended interval dosing (EID) in subjects who have previously been treated with natalizumab standard interval dosing (SID) for at least 12 months, in relation to continued SID treatment |
L’obiettivo primario dello studio è di valutare l’efficacia di natalizumab EID in soggetti che sono stati precedentemente trattati con natalizumab SID per almeno 12 mesi, in relazione al trattamento SID continuato, |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate additional clinical and MRI based efficacy endpoints, and safety of EID in subjects who have previously been treated with natalizumab SID for at least 12 months, in relation to continued SID treatment. |
Gli obiettivi secondari consistono nel valutare ulteriori endpoint di efficacia clinica e basati su risonanza magnetica (RM), nonché la sicurezza del dosaggio a intervallo esteso (EID) in soggetti precedentemente trattati con dosaggio a intervallo standard (SID) di natalizumab per almeno 12 mesi rispetto al trattamento continuo con SID. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Ability of the participant to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations. • Diagnosis of relapsing remitting multiple sclerosis (RRMS) according to the McDonald criteria [Thompson 2018]. • Treatment with natalizumab as disease-modifying monotherapy for RRMS that is consistent with the approved dosing for a minimum of 12 months prior to randomization. The participant must have received at least 11 doses of natalizumab in the 12 months prior to randomization with no missed doses in the 3 months prior to randomization. • Expanded Disability Status Scale (EDSS) <=5.5 at screening. • No relapses in the last 12 months prior to randomization, as determined by the enrolling Investigator NOTE: Other protocol-defined inclusion criteria may apply. |
• Capacità del partecipante di comprendere l’obiettivo e i rischi dello studio e di fornire un consenso informato firmato e datato e l’autorizzazione all’utilizzo di informazioni sanitarie riservate in conformità alle normative nazionali e locali sulla privacy dei partecipanti. • Diagnosi di sclerosi multipla recidivante remittente (SMRR) secondo i criteri di McDonald [Thompson 2018]. • Trattamento con natalizumab come monoterapia modificante la malattia per la SMRR che sia coerente con il dosaggio approvato per un minimo di 12 mesi precedenti la randomizzazione. Il partecipante deve avere ricevuto almeno 11 dosi di natalizumab nei 12 mesi precedenti la randomizzazione senza aver saltato alcuna dose nei 3 mesi precedenti la randomizzazione. • Stato della Scala di invalidità espansa (EDSS) <= 5,5 allo screening. • Nessuna recidiva negli ultimi 12 mesi precedenti la randomizzazione, come determinato dallo Sperimentatore responsabile del reclutamento Nota: Potrebbero applicarsi altri criteri di inclusione definiti dal protocollo |
|
E.4 | Principal exclusion criteria |
• Primary and secondary progressive multiple sclerosis (MS). • MRI positive for Gd-enhancing lesions at screening. • Participants for whom MRI is contraindicated (e.g., have a contraindicated pacemaker or other contraindicated implanted metal device, have suffered, or are at risk for, side effects from Gd, or have claustrophobia that cannot be medically managed). • History of any clinically significant (as determined by the Investigator) cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic (including diabetes), urologic, pulmonary, neurologic (except for RRMS), dermatologic, psychiatric, renal, or other major disease that would preclude participation in a clinical study, in the opinion of the Investigator. • Presence of anti-natalizumab antibodies at screening. NOTE: Other protocol-defined exclusion criteria may apply. |
• Sclerosi multipla (SM) primariamente e secondariamente progressiva. • RM positiva per lesioni captanti il gadolinio (Gd) allo screening. • Partecipanti con controindicazione alla RM (ad es. portatori di un pacemaker controindicato o di altri dispositivi metallici impiantati controindicati; con pregressi, o a rischio di, effetti collaterali da Gd o affetti da claustrofobia non gestibile dal punto di vista medico). • Anamnesi di qualsiasi patologia cardiaca, endocrinologica, ematologica, epatica, immunologica, metabolica (incluso il diabete), urologica, polmonare, neurologica (diversa dalla SMRR), dermatologica, psichiatrica o renale clinicamente significativa (in base al giudizio dello Sperimentatore) o di altra patologia grave che possa precludere la partecipazione a uno studio clinico, a parere dello Sperimentatore. • Positività agli anticorpi anti-natalizumab allo screening. Nota: Potrebbero applicarsi altri criteri di esclusione definiti dal protocollo |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of New or Newly Enlarging T2 Hyperintense Lesions at Week |
Numero di lesioni, nuove o di recente espansione, iperintense in T2 alla Settimana 48 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Evaluation Committee (INEC) •Number of new Gadolinium (Gd) Enhancing and new T1 Hypointense Lesions at Weeks 24, 48 and 72 •Annualized Relapse Rate at Weeks 48 and 72 •Number of New or Newly Enlarging T2 Hyperintense Lesions at Weeks 24 and 72 •Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
• Tempo alla prima recidiva come convalidato da un Comitato indipendente di valutazione neurologica (Independent Neurology Evaluation Committee, INEC) • Numero di lesioni di nuova espansione captanti gadolinio (Gd) e di lesioni ipointense in T1 nuove alle Settimane 24, 48 e 72 • Tasso di recidiva annualizzato alle Settimane 48 e 72 • Numero di lesioni, nuove o di recente espansione, iperintense in T2 alle Settimane 24 e 72 • Numero di partecipanti con eventi avversi (AE) ed eventi avversi seri (SAE) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Variable time frames throughout the study |
Intervalli di tempo variabili durante lo studio |
|
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 | 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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
gruppo di trattamento (natalizumab SID, natalizumab EID) |
treatment group (natalizumab SID; natalizumab EID) |
|
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
Belgium |
Canada |
France |
Germany |
Israel |
Italy |
Netherlands |
New Zealand |
Spain |
United Kingdom |
United States |
|
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
|
|
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 | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |