E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alzheimer’s disease (AD) |
Malattia di Alzheimer |
|
E.1.1.1 | Medical condition in easily understood language |
AD is a chronic neurodegenerative disease that destroys memory and other important mental functions. |
L'AD è un disturbo progressivo che causa problemi con la memoria ed altre importanti funzioni mentali. |
|
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 | 10001897 |
E.1.2 | Term | Alzheimer's disease (incl subtypes) |
E.1.2 | System Organ Class | 100000004852 |
|
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 |
To evaluate the long-term safety and tolerability of continued treatment with subcutaneous (SC) gantenerumab at target dose in participants with AD who received gantenerumab in open-label extension (OLEs) of Studies WN25203 or WN28745 |
Valutare la sicurezza e la tollerabilità a lungo termine della prosecuzione del trattamento con gantenerumab s.c. alla dose target in pazienti affetti da AD che hanno ricevuto gantenerumab nella fase OLE dello studio WN25203 o dello studio WN28745 |
|
E.2.2 | Secondary objectives of the trial |
Not applicable |
Non Applicabile |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- All participants who completed the OLEs of Studies WN25203 or WN28745 (i.e., latest version of protocol in their countries, and did not discontinue study drug early) are eligible to participate in this study
- For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 16 weeks after the last dose of study drug
|
- Sono considerati idonei all’ingresso nello studio in oggetto tutti i pazienti che hanno partecipato alla fase OLE dello studio WN25203 o dello studio WN28745 e l’hanno completata (ovvero ultima versione del protocollo nei rispettivi paesi e senza interruzione anticipata del trattamento sperimentale). - Per le donne in età fertile: consenso a praticare l’astinenza dai rapporti eterosessuali o a fare uso di metodi contraccettivi con tasso di insuccesso < 1% all’anno durante il periodo di trattamento e per almeno 16 settimane dopo la somministrazione dell’ultima dose del trattamento sperimentale |
|
E.4 | Principal exclusion criteria |
- Prematurely discontinued from the OLEs of Studies WN25203 or WN28745 or from study drug for any reason - Any medical condition that the investigator or Sponsor determines may jeopardize the participant’s safety if he or she continues to receive study treatment - If the participant is unlikely to benefit from gantenerumab therapy, based on disease progression or other factors, or if study participation is otherwise not in the participant’s best interest, by determination of the investigator or Sponsor - Any investigational treatment other than gantenerumab during or since completion of the OLEs of Studies WN25203 or WN28745 - Pregnancy - Evidence of disseminated leptomeningeal hemosiderosis - Evidence of intracerebral macrohemorrhage |
- interruzione anticipata, per qualsiasi motivo, della partecipazione alla fase OLE dello studio WN25203 o dello studio WN28745 oppure del trattamento sperimentale - presenza di una condizione medica che, a giudizio dello sperimentatore o dello sponsor, potrebbe compromettere la sicurezza del/della paziente se questi/a continuasse ad assumere il trattamento sperimentale - eventualità in cui sia improbabile che il/la paziente tragga beneficio dalla terapia con gantenerumab, in base alla progressione della malattia o ad altri fattori, oppure eventualità in cui, a giudizio dello sperimentatore o dello sponsor, la partecipazione allo studio non risulti essere nel miglior interesse del/della paziente - assunzione di un trattamento sperimentale diverso da gantenerumab durante la fase OLE dello studio WN25203 o dello studio WN28745 o dopo il suo completamento - gravidanza - evidenza di emosiderosi leptomeningea disseminata (ossia più di tre emosiderosi leptomeningee focali) - evidenza di macroemorragia intracerebrale. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Incidence, nature, severity, and timing of adverse events and serious adverse events
2. Changes from baseline in vital signs, blood tests
3. Changes from baseline in electrocardiogram
4. Changes from baseline in the Columbia-Suicide Severity Rating Scale (C SSRS)
5. Incidence, nature, severity, and timing of magnetic resonance imaging (MRI) safety findings: amyloid-related imaging abnormality–edema/effusion (ARIA E) and amyloid-related imaging abnormality–hemosiderin depositions (ARIA H)
6. Incidence, nature, severity, and timing of injection-site reaction (ISRs)
7. Number and proportion of anti-drug antibody (ADA)-positive and ADA-negative participants during both the treatment and follow-up periods
8. Incidence of treatment discontinuations for adverse events
9. Incidence of adverse events of special interest
|
1 incidenza, natura, gravità e tempistica degli AE e dei SAE 2 variazioni, rispetto al basale dello studio in oggetto, nelle misurazioni dei segni vitali, nei valori delle analisi del sangue 3 variazioni, rispetto al basale dello studio in oggetto nei parametri degli ECG 4 variazioni, rispetto al basale dello studio in oggetto nel punteggio della scala C-SSRS 5 incidenza, natura, gravità e tempistica dei riscontri RM in termini di sicurezza: ARIA-E e ARIA-H 6 incidenza, natura, gravità e tempistica delle reazioni al sito d’iniezione (Injection-Site Reaction, ISR) 7 numero e percentuale di pazienti ADA-positivi e ADA-negativi durante la fase di trattamento e di follow-up 8 incidenza delle interruzioni del trattamento a causa di AE 9 incidenza degli AE di particolare interesse. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to 4 weeks after the last dose of the study drug
2. Baseline (Day 1) to 4 weeks after the last dose of the study drug
3. At baseline and unscheduled visit (UV)
4-5. Baseline, Week 24, Week 52, Week 76, Week 104, follow-up (FU)/ early termination (ET) visit, UV
6. Up to 4 weeks after the last dose of the study drug
7. Day 1, Week 52, Week 104, FU/ET visit
8-9. Up to 4 weeks after the last dose of the study drug
|
1. Fino a 4 settimane dopo l'ultima dose del farmaco in studio 2. Basale (giorno 1) a 4 settimane dopo l'ultima dose del farmaco in studio 3. Alla visita basale e alla visita non programmata (UV) 4-5. Basale, settimana 24, settimana 52, settimana 76, settimana 104, visita di follow-up (FU) / visita di termine anticipata (ET), UV 6. Fino a 4 settimane dopo l'ultima dose del farmaco in studio 7. Giorno 1, settimana 52, settimana 104, visita FU / ET 8-9. Fino a 4 settimane dopo l'ultima dose del farmaco in 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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Canada |
Chile |
Japan |
Korea, Republic of |
Mexico |
Russian Federation |
Turkey |
United States |
Belgium |
Denmark |
Italy |
Netherlands |
Poland |
Spain |
Switzerland |
United Kingdom |
Argentina |
|
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
|
The end of study is defined as the date when the last participant last visit (LPLV) occurs or the date on which the last data point required for safety follow-up is received from the participant in the study. |
La fine dello studio è definita come la data in cui si verifica l'ultima visita dell'ultimo partecipante (LPLV) o la data in cui l'ultimo punto di dati richiesto per il follow-up di sicurezza viene ricevuto dal partecipante allo studio. |
|
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 | 10 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |