E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generalized Myasthenia Gravis |
Miastenia Gravis generalizzata |
|
E.1.1.1 | Medical condition in easily understood language |
Generalized Myasthenia Gravis |
Miastenia Gravis generalizzata |
|
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 | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10071942 |
E.1.2 | Term | Myasthenia gravis and related conditions |
E.1.2 | System Organ Class | 100000004859 |
|
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 assess the efficacy of ravulizumab compared with placebo in the treatment of gMG based on the improvement in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) profile. |
Verificare l'efficacia di Ravulizumab comparata al placebo nel trattamento della gMG sulla base dei miglioramenti nel profilo MG-ADL (Myasthenia Gravis- Activities of Daily Living) |
|
E.2.2 | Secondary objectives of the trial |
- To assess the efficacy of ravulizumab compared with placebo in the treatment of gMG based on the improvement in the Quantitative Myasthenia Gravis (QMG) total score. - To assess the efficacy of ravulizumab compared with placebo in the treatment of gMG based on the improvement in quality of life measures. - To assess the efficacy of ravulizumab compared with placebo in the treatment of gMG based on other efficacy endpoints. |
- Verificare l'efficacia di Ravulizumab comparata con il placebo nel trattamento della gMG sulla base dei miglioramenti nella scala QMG (Quantitative Myasthenia Gravis). - Valutare l'efficacia di ravulizumab comparata con il placebo nel trattamento della gMG sulla base dei miglioramenti nelel misurazioni della qualità della vita - Valutare l'efficacia di ravulizumab comparata con il placebo nel trattamento della gMG sulla base di altri endpoints di efficacia |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female patients = 18 years of age • Diagnosed with MG at least 6 months (180 days) prior to the date of the Screening Visit as confirmed by protocol-specific criteria • Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening • MG-ADL profile must be = 6 at screening and randomization (Day 1) • Vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating study drug to reduce the risk of meningococcal infection (N meningitidis). • Body weight = 40 kg at the time of screening • Patients of childbearing potential and patients with partners of childbearing potential must follow protocol-specified contraception guidance for avoiding pregnancy while on treatment and for 8 months after last dose of study drug |
- Pazienti di entrambi i sessi con età uguale o superiore a 18 anni - Diagnosi di Miastenia Gravisalmeno 6 mesi (180 giorni) prima delal data della visita di screening come confermato da criteri specifici del protocollo - Classificazione clinica della Miastenia Gravis da II a IV allo screening, sulla base della classificazione Myasthenia Gravis Foundation of America Clinical Classification - il profilo MG-ADL deve essere = 6 allo screening e alla randomizzazione (giorno 1) - I pazienti devono essere vaccinati contro infezioni meningococciche entro 3 anni prima, o al massimo al momento di iniziare il trattamento dello studio, per ridurre i rischi di infezione meningococcica (N Meningitidis) - peso corporeo = 40 kg al momento dello screening - le pazienti fertili e i pazienti con compagne fertili devono seguire le indicazioni relative alla contraccezione del protocollo e devono evitare una gravidanza durante il trattamento e per 8 mesi dopo l'ultima dose del farmaco in studio. |
|
E.4 | Principal exclusion criteria |
Medical Conditions: • Any active or untreated thymoma. History of thymic carcinoma or thymic malignancy • History of thymectomy, thymomectomy, or any thymic surgery within the 12 months prior to screening • History of N meningitidis infection • Human immunodeficiency virus (HIV) infection • History of hospitalization for = 24 hours, for any reason, within the 4 weeks (28 days) prior to screening • Females who plan to become pregnant during the study, or are currently pregnant or breastfeeding, or who have a positive pregnancy test result at screening or on Day 1 • History of unexplained infections • Active systemic bacterial, viral, or fungal infection within 14 days prior to study drug administration on Day 1 • Presence of fever = 38°C (100.4°F) within 7 days prior to study drug administration on Day 1
Prior/Concomitant Therapy •Use of the following within the time period specified below: - IVIg within the 4 weeks (28 days) prior to randomization (Day 1) - Use of PE within the 4 weeks (28 days) prior to randomization (Day 1) - Use of rituximab within the 6 months (180 days) prior to screening • Patients who have received previous treatment with complementinhibitors (eg, eculizumab |
Condizione medica - Qualsiasi timoma attivo o non trattato. Storia di carcinoma timico o tumore timico - Anamnesi di timectomia, timomectomia o qualsiasi altra chirurgia al timo entro i 12 mesi precedenti allo screening - Anamnesi di infezione da N Meningitidis - Infezione da virus HIV - Storia di ospedalizzazione per = 24 ore, per qualsiasi motivo, entro le 4 settimane (28 giorni) prima dello screening - Donne che stanno pianificando una gravidanza durante lo studio, o che sono attualmente incinte o in allattamento, o che hanno un test di gravidanza positivo allo screening o al giorno 1 - Storia di infezioni inspiegabili - Infezioni sistemiche fungine, batteriche o virali entro 14 giorni prima della somministrazione del farmaco al Giorno 1 - Febbre = 38° entro 7 giorni prima della somministrazione del farmaco al Giorno 1
Terapie precedenti/concomitanti - Utilizzo dei seguenti farmaci durante il periodo specificato di seguito: - IVIg entro le 4 settimane (28 giorni) prima della randomizzazione (giorno 1) - Uso di PE entro le 4 settimane (28 giorni) prima della randomizzazione (giorno 1) - Uso di Rituximab entro 6 mesi (180 giorni) prima dello screening - pazienti che hanno ricevuto trattamenti con inibitori del complemento (ad es. eculizumab) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from Baseline in MG-ADL total score |
Cambiamento nel punteggio MG-ADL rispetto al basale. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At Week 26 of the Randomized-Controlled Period. |
Alal settimana 26 del periodo Randomizzato/Controllato |
|
E.5.2 | Secondary end point(s) |
• Change from Baseline in QMG total score. • Change from Baseline in the Revised 15-Component Myasthenia Gravis Quality of Life (MG-QOL15r) score • Change from Baseline in Neuro-QOL Fatigue score • Improvement from Baseline of at least 3 points in the MG-ADL total score • Improvement from Baseline of at least 5 points in the QMG total score |
- Cambiamento nel punteggio QMG rispetto al basale - Cambiamento rispetto al basale nel punteggio MG-QOL15r - Cambiamento rispetto al basale del punteggio nella Neuro-QOL Fatigue - Miglioramento rispetto al basale di almeno 3 punti nel punteggio totale MG-ADL - Miglioramento rispetto al basale di almeno 5 punti nel punteggio totale QMG. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At Week 26 |
Alla settimana 26 |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 |
Canada |
Israel |
Japan |
Korea, Republic of |
Russian Federation |
United States |
Austria |
Belgium |
Czechia |
Denmark |
France |
Germany |
Italy |
Netherlands |
Portugal |
Spain |
Switzerland |
United Kingdom |
|
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
|
LVLS in the study or last scheduled procedure shown in the Schedule of Activities for the last patient in the study globally |
LPLV per lo studio oppure l'ultima procedura mostrata nella tabella delle attività per un paziente condotta al livello globale. |
|
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 | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |