E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Congenital Myasthenic Syndromes (CMS) |
Sindromi Miasteniche Congenite (SMC) |
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E.1.1.1 | Medical condition in easily understood language |
Congenital Myasthenic Syndromes (CMS) |
Sindromi Miasteniche Congenite (SMC) |
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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 | 10028424 |
E.1.2 | Term | Myasthenic syndrome |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028425 |
E.1.2 | Term | Myasthenic syndromes in diseases classified elsewhere |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
To characterize the long-term safety and tolerability of amifampridine phosphate in patients with Congenital Myasthenic Syndromes (CMS). |
Definire la sicurezza e la tollerabilità di un trattamento a lungo termine con amifampridina fosfato in pazienti con Sindromi Miasteniche Congenite (SMC). |
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E.2.2 | Secondary objectives of the trial |
To assess the clinical efficacy of amifampridine phosphate over time in patients with Congenital Myasthenic Syndromes (CMS) based on change in Subject Global Impression (SGI) Scores. |
Valutare l’efficacia clinica di amifampridina fosfato nel tempo, in pazienti con Sindromi Miasteniche Congenite (SMC) in base al cambiamento dei punteggi derivati dal questionario sulla impressione globale del soggetto (Subject Global Impression - SGI) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Participated in the CMS-001 study or failed to meet screening or randomization criteria of Protocol CMS-001 but considered to have potential clinical benefit from treatment with amifampridine phosphate. 2. Willing and able to provide written informed consent by patient or guardian after the nature of the study has been explained and before the start of any research-related procedures. 3. Female patients of childbearing potential defined according to the Clinical Trial Facilitation Group - CTFG guidelines must have a negative urine pregnancy test and must practice an effective, reliable contraceptive regimen according to the CTFG guidelines criteria during the study and for up to 30 days following discontinuation of treatment. 4. Ability to participate in the study based on overall health of the patient and disease prognosis, as applicable, in the opinion of the Investigator; and able to comply with all requirements of the protocol, including completion of study questionnaires. |
1. Pazienti inclusi nello studio CMS-001 o che non hanno soddisfatto i criteri per essere inclusi allo Screening o alla Randomizzazione del Protocollo CMS-001 ma che potrebbero avere un potenziale beneficio clinico dal trattamento con amifampridina fosfato. 2. Disposti e in grado di fornire il consenso informato scritto, fornito direttamente dal paziente o dai genitori/tutori legali, dopo che la tipologia dello studio sia stata spiegata e prima che sia iniziata qualsiasi procedura correlata con lo studio. 3. Donne in età fertile, definita in accordo ai criteri della linea guida del Clinical Trial Facilitation Group - CTFG devono avere un test di gravidanza urinario negativo; devono, inoltre, utilizzare un metodo contraccettivo efficace e affidabile in accordo alle raccomandazioni della linea guida del CTFG durante lo studio e per i 30 giorni successivi alla fine del trattamento. 4. In grado di partecipare allo studio in base allo stato generale di salute del paziente e alla prognosi di malattia e in base al giudizio dello Sperimentatore, in grado di soddisfare tutti i requisiti del protocollo, compreso il completamento dei questionari previsti dallo studio. |
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E.4 | Principal exclusion criteria |
Individuals who meet any of the exclusion criteria in the protocol CMS-001 or those listed below are not eligible to participate in the study: 1. Epilepsy and currently on medication. 2. Clinically significant abnormalities in 12 lead ECG, in the opinion of the Investigator. 3. Breastfeeding or pregnant at Screening or planning to become pregnant at any time during the study. 4. Intolerable amifampridine-related side effects 5. Treatment with an investigational drug (other than amifampridine) or device while participating in this study. 6. Any medical condition that, in the opinion of the Investigator, might interfere with the patient’s participation in the study, poses an added risk for the patient, or confound the assessment of the patient. |
I soggetti che soddisfano uno qualsiasi dei criteri di esclusione del protocollo CSM-001 o uno qualsiasi dei criteri di esclusione elencati di seguito non sono idonei a partecipare allo studio CMS-002: 1. Epilessia e attualmente in terapia per l'epilessia. 2. Un elettrocardiogramma (ECG a 12 derivazioni) che, secondo il parere dello Sperimentatore, presenta anormalità clinicamente significative. 3. In allattamento o in stato di gravidanza alla visita di Screening o che pianifichino una gravidanza nel corso del periodo di studio. 4. Effetti collaterali intollerabili correlati al trattamento con amifampridina. 5. Trattamento con un farmaco sperimentale (diverso da amifampridina) o con un dispositivo medico nel corso del periodo di studio. 6. Qualsiasi condizione clinica che, secondo il parere dello Sperimentatore, potrebbe interferire con la partecipazione del paziente allo studio, che potrebbe comportare un ulteriore rischio per il paziente, o che potrebbe rendere poco chiara la valutazione del paziente. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of the study is the safety and tolerability of amifampridine. Safety will be assessed by the incidence of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs). Vital signs, 12-lead ECGs, clinical laboratory tests, physical examination findings, and concomitant medications will also be evaluated. |
Sicurezza (endpoint primario): la sicurezza verrà valutata in base all’incidenza degli eventi avversi verificatisi nel corso del trattamento (TEAEs), inclusi gli eventi avversi seri (SAEs). Saranno anche valutati i risultati ottenuti dalle valutazioni dei segni vitali, degli ECG a 12 derivazioni, dei test clinici di laboratorio, dell’esame obiettivo e dei trattamenti concomitanti. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The safety and tolerability of amifampridine will be evaluated at months 3, 6, 9, 12, 15 and 21 after inclusion in the study. |
La sicurezza e tollerabilità del farmaco sarà valutata al mese 3, 6, 9, 12, 15 e 21 dall' inclusione nello studio. |
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E.5.2 | Secondary end point(s) |
The secondary endpoint of the study is changes in the Subject Global Impression (SGI) scores over time. |
L’efficacia della amifampridina sarà valutata in base ai cambiamenti nel corso del tempo nei punteggi del questionario Impressione Globale del Soggetto - Subject Global Impression (SGI). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoint of the study will be assessed from baseline at months 3, 6, 9, 12, 15 and 21. |
L'endpoint secodario dello studio sarà valutato al mese 3,6,9,12,15 e 21 dall'inclusione nello studio. |
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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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | 2 |
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 | Information not present in EudraCT |
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
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LVLS or until amifampridine is approved by regulatory agencies for the treatment of Congenital Myasthenic Syndromes (CMS) or the development program of amifampridine is discontinued for this indication, whichever occurs first |
LVLS o fino a quando l'amifampridina viene approvata dalle agenzie regolatorie per il trattamento delle sindromi miasteniche congenite (SMC) o lo sviluppo clinico di amifampridina viene interrotto per l' indicazione in studio, a seconda di quale evento si verifichi per primo |
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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 | 2 |
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 | 2 |
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 | 0 |