E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Multiple Sclerosis (MS) |
Sclerosi multipla (SM) |
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E.1.1.1 | Medical condition in easily understood language |
Multiple Sclerosis (MS) |
Sclerosi multipla (SM) |
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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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048393 |
E.1.2 | Term | Multiple sclerosis relapse |
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 immunogenicity of natalizumab 300 mg SC administered to subjects with relapsing MS. |
L’obiettivo primario di questo studio è valutare l’immunogenicità di natalizumab 300 mg somministrato per via SC ai soggetti con RMS. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are as follows:
• To evaluate the safety of natalizumab SC injections.
• To evaluate the efficacy of natalizumab SC injections on relapses and on new MRI lesions. |
gli obiettivi secondari sono i seguenti:
• Valutare la sicurezza delle iniezioni SC di natalizumab.
• Valutare l’efficacia delle iniezioni SC di natalizumab in termini di recidive e nuove lesioni alla risonanza magnetica per immagini (RMI).
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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 |
A pharmacogenomics study ("PGx study") is being done in connection with the main study and is being conducted as there is growing evidence that differences in people's genes known as DNA or RNA (genetic material) may cause differences in the way they respond to medicine. These differences in how a drug affects someone may be due to differences in peoples' genes and impact how the medicine works. These differences may also affect why some people get certain diseases and the way a person gets sick or gets better. Finally, studying genetic differences may lead to understanding why some people have unexpected reactions to medicines during a study.
Subject participation in the PGx study is optional.
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è prevista l’esecuzione di un sottostudio di farmacogenomica il cui razionale è l’evidenza che, differenze a livello genetico negli individui, possono determinare una diversa risposta al farmaco. Queste differenze possono influenzare l’efficacia del farmaco sull’organismo o determinare l’isorgenza di patologie. Inoltre lo studio genetico può aiutare a comprendere perchè alcune persone presentano reazioni inattese al farmaco di studio. La partecipazione del soggetto al sottostudio è opzionale. |
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E.3 | Principal inclusion criteria |
- Must have documented diagnosis of RMS at screening.
- Must fall within the therapeutic indications stated in the locally approved label for natalizumab.
- Must have an EDSS score from 0 to 6.5, inclusive. |
- documentata storia di sclerosi multipla recidivante allo screening
- deve rientrare nell’indicazione terapeutica approvata per natalizumab
- deve avere un ponteggio EDSS da 0 a 6.5 incluso.
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E.4 | Principal exclusion criteria |
- Any prior use of natalizumab.
- Positive for anti-natalizumab antibodies at screening.
- Treatment with immunomodulatory injections (including IFN-β and glatiramer acetate) within 2 weeks prior to Screening. |
- documentata storia di sclerosi multipla recidivante allo screening
- deve rientrare nell’indicazione terapeutica approvata per natalizumab
- deve avere un ponteggio EDSS da 0 a 6.5 incluso.
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects with persistent anti-natalizumab antibodies over 48 weeks. Persistent anti-natalizumab antibodies are defined as 2 positive anti-natalizumab test results separated by at least 6 weeks, with at least 1 positive test result occurring at or after the Week 24 Visit. |
La percentuale di soggetti con anticorpi anti-natalizumab persistenti nelle 48 settimane. Gli anticorpi anti-natalizumab persistenti sono definiti come 2 risultati positivi all'esame anti-natalizumab a distanza di almeno 6 settimane, con almeno 1 risultato positivo all'esame in occasione o dopo la visita della Settimana 24. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• The proportion of subjects with transient anti-natalizumab antibodies over 48 weeks.
• The proportion of subjects with post-injection AEs including hypersensitivity reactions, anaphylactic reactions and other AEs occurring within 1 hour after subcutaneous natalizumab dosing.
• The proportion of subjects with clinical relapse; or with new or enlarging T2 lesion(s), as determined by a central MRI reading center, over 48 weeks. Clinical relapse is defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours, and accompanied by new objective neurological findings upon examination by the Neurologist. The subject must have had objective signs on the neurologist’s examination that confirm the event.
• The proportion of subjects with Gd-enhancing lesion(s), as determined by a central MRI reading center, over 48 weeks.
• The proportion of subjects with AEs and SAEs.
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• La percentuale di soggetti con anticorpi anti-natalizumab transitori nelle 48 settimane.
• La percentuale di soggetti con eventi avversi (EA) in seguito all’iniezione, tra cui reazioni di ipersensibilità, reazioni anafilattiche e altri EA manifestati entro 1 ora dalla somministrazione di natalizumab SC.
• La percentuale di soggetti con recidiva clinica o con lesione(i) nuova(e) o ingrandita(e) in T2, come evidenziato dalla lettura centralizzata dell’MRI, nelle 48 settimane. La recidiva clinica è definita come nuovi o ricorrenti sintomi neurologici non associati a febbre o infezione, della durata di almeno 24 ore, e accompagnati da nuovi riscontri neurologici obiettivi in base al giudizio del neurologo. Il soggetto deve presentare segni obiettivi alla visita neurologica che confermino l’evento.
• La percentuale di soggetti con lesione(i) captante(i) il gadolinio (Gd), come evidenziato dalla lettura centralizzata dell’MRI, nelle 48 settimane.
• La percentuale di soggetti con EA ed eventi avversi seri (serious adverse events, SAE).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |