E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Alzheimer's Disease |
Malattia di Alzheimer |
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E.1.1.1 | Medical condition in easily understood language |
Alzheimer's Disease |
Malattia di Alzheimer |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001896 |
E.1.2 | Term | Alzheimer's disease |
E.1.2 | System Organ Class | 100000004852 |
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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 |
Investigation of the effect of bepranemab versus (vs) placebo on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) up to Week 80 in study participants with prodromal or mild Alzheimer's Disease (AD) |
Studio dell’effetto di bepranemab rispetto a (vs) placebo sulla Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) fino alla Settimana 80 nei partecipanti allo studio con Malattia di Alzheimer (AD) da prodromica a lieve |
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E.2.2 | Secondary objectives of the trial |
-Evaluation of the safety and tolerability of bepranemab vs. placebo over 80 weeks in study participants with prodromal or mild Alzheimer's Disease (AD) -Investigation of the effect of bepranemab on tau burden in the brain as measured by [18F]Genentech tau probe 1 (GTP1) positron emission tomography (PET) imaging in study participants with prodromal or mild AD -Investigation of the effect of bepranemab vs placebo on cognitive and functional measures over time in study participants with prodromal or mild AD -Characterisation of the pharmacokinetic (PK) of bepranemab following repeated intravenous (iv) administration in study participants with prodromal or mild AD |
-Valutazione di sicurezza e tollerabilità di bepranemab vs placebo nell’arco di 80 settimane nei partecipanti allo studio con Malattia di Alzheimer (AD) da prodromica a lieve -Studio dell’effetto di bepranemab sul carico della tau all’interno del cervello misurato mediante tracciante [18F]Genentech tau probe 1 (GTP1) per tomografia a emissione di positroni (PET) nei partecipanti allo studio con AD da prodromica a lieve -Studio dell’effetto di bepranemab vs placebo sulle misure cognitive e funzionali nel tempo nei partecipanti allo studio con AD da prodromica a lieve -Caratterizzazione della farmacocinetica (PK) di bepranemab a seguito di ripetute somministrazioni per via endovenosa (ev) nei partecipanti allo studio con AD da prodromica a lieve |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- 50 to 80 years of age - diagnosis of prodromal/mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or mild AD according to National Institute of Aging-Alzheimer's Association (NIA-AA) - a global Clinical Dementia Rating (CDR) score of 0.5 to 1.0 and CDRMemory Box (CDRMB) score =0.5 at Screening and Baseline - Score of =85 for the delayed recall domain of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) at Screening - Mini-Mental State Examination (MMSE) score =20 at Screening - Participant has an identified informant that has and will maintain sufficient contact (minimum of 5 hours per week) with the participant to be able to provide accurate information on the participant's cognitive, functional, and emotional states and of the participant's personal care - At least 6 years of formal education after the age of 5 or work experience to exclude mental deficits other than prodromal or mild AD dementia - evidence of cerebral Aß accumulation by either positive amyloid assessment by either positron emission tomography (PET) scan or cerebrospinal fluid pTau181/Aß1-42 ratio assessment |
- età compresa tra 50 e 80 anni - diagnosi di deterioramento cognitivo prodromico/lieve (MCI) dovuto alla Malattia di Alzheimer (AD) o AD lieve secondo il National Institute of Aging-Alzheimer's Association (NIA-AA) - punteggio globale del Clinical Dementia Rating (CDR) da 0,5 a 1,0 e punteggio del CDRMemory Box (CDRMB) =0,5 allo screening e al basale - punteggio per il dominio della memoria differita della Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) =85 allo screening - punteggio del Mini-Mental State Examination (MMSE) =20 allo screening - il partecipante ha un informatore identificato, con cui mantiene e manterrà contatti sufficienti (minimo 5 ore alla settimana), affinché questi possa fornire informazioni accurate riguardo allo stato cognitivo, funzionale ed emotivo del partecipante, nonché alla sua cura personale - almeno 6 anni di istruzione formale dopo i 5 anni di età o esperienza lavorativa che escluda deficit mentali diversi dalla demenza di tipo AD da prodromica a lieve - evidenza di accumulo cerebrale di Aß mediante valutazione amiloide positiva eseguita con tomografia a emissione di positroni (PET) oppure valutazione del rapporto pTau181/Aß1-42 nel liquido cefalorachidiano |
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E.4 | Principal exclusion criteria |
- any evidence of a condition that may affect cognition other than AD - contraindications to PET imaging - Inability to tolerate or contraindication to magnetic resonance imaging - any serious medical condition or abnormality that in the opinion of the investigator would preclude safe participation in and completion of the study or interfere with study assessments and/or study interpretation - alcohol or drug abuse within 2 years of screening - use of any experimental therapy within the past 6 months (or 5 half lives) prior to screening - previous treatment with medication intended to treat a neurodegenerative disorder (other than AD) within 1 year of screening - chronic daily treatment with atypical antipsychotics, opiates or opioids, benzodiazepines, barbiturates, hypnotics, or any medication with clinically significant centrally acting antihistamine or anticholinergic activitiy - received treatment with monoclonal antibodies (mAbs), cytokines, immunoglobulins, or other blood products within 3 months or 5 half-lives (whichever is longer) prior to first dosing |
- qualsiasi evidenza di patologia, diversa da AD, che potrebbe influire sulla sfera cognitiva - controindicazioni alla PET - incapacità di tollerare o controindicazione alla risonanza magnetica per immagini - qualsiasi patologia medica o anomalia che, secondo il parere dello sperimentatore, precluderebbe la partecipazione in sicurezza e il completamento dello studio oppure interferirebbe con le valutazioni e/o l’interpretazione dello studio - abuso di alcool o stupefacenti nei 2 anni precedenti lo screening - uso di qualsiasi terapia sperimentale negli ultimi 6 mesi (o 5 emivite) precedenti lo screening - precedente trattamento con farmaci indicati al trattamento di un disturbo neurodegenerativo (diverso da AD) entro 1 anno dallo screening - trattamento giornaliero cronico con antipsicotici atipici, oppiacei o oppioidi, benzodiazepine, barbiturici, ipnotici o qualsiasi farmaco con azione antistaminica o anticolinergica clinicamente significativa che agisce a livello del sistema nervoso centrale - trattamento con anticorpi monoclonali (mAbs), citochine, immunoglobuline, o altri prodotti ematici ricevuto nei 3 mesi o 5 emivite (a seconda di quale sia il periodo più lungo) precedenti la prima somministrazione |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change from Baseline to Week 80 in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) total score |
1. Variazione dal basale alla Settimana 80 nel punteggio totale del Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. From from Baseline to Week 80 |
1. Dal basale alla Settimana 80 |
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E.5.2 | Secondary end point(s) |
1. Incidence of treatment-emergent adverse events (TEAEs) 2. Incidence of treatment-emergent serious adverse events (TESAEs) 3. Incidence of TEAEs leading to discontinuation or death 4. Incidence of Drug-related TEAEs 5. Change from Baseline in suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) 6. Change from Baseline to Week 56 and Week 80 on indices of tau burden in the brain as measured by [18F]Genentech tau probe 1 (GTP1) positron emission tomography (PET) 7. Change from Baseline to Week 56 and Week 80 in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) 8. Change from Baseline to Week 56 and Week 80 in AmsterdamInstrumental Activities of Daily Living (A-iADL) 9. Change from Baseline to Week 56 and Week 80 in Mini-Mental State Examination (MMSE) total score 10. Serum concentrations of bepranemab over the 80-week Double-blind Treatment Period |
1. Incidenza di eventi avversi emergenti dal trattamento (TEAE) 2. Incidenza di eventi avversi seri emergenti dal trattamento (TESAE) 3. Incidenza dei TEAE che portano a interruzione o decesso 4. Incidenza dei TEAE correlati al farmaco 5. Variazione rispetto al basale nell’ideazione suicidaria e nel comportamento valutato mediante la scala di valutazione della gravità della suicidalità della Columbia University (C-SSRS) 6. Variazione dal basale alla Settimana 56 e alla Settimana 80 negli indici del carico della tau all’interno del cervello misurato mediante tracciante [18F]Genentech tau probe 1 (GTP1) per tomografia a emissione di positroni (PET) 7. Variazione dal basale alla Settimana 56 e alla Settimana 80 nella sottoscala Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) 8. Variazioni dal basale alla Settimana 56 e alla Settimana 80 nell’Amsterdam-Instrumental Activities of Daily Living (A-iADL) 9. Variazione dal basale alla Settimana 56 e alla Settimana 80 nel punteggio totale del Mini-Mental State Examination (MMSE) 10. Concentrazioni sieriche di bepranemab durante l’intero periodo di trattamento in doppio cieco di 80 settimane |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 - 4: From Baseline to the Safety Follow-Up (Week 152) 6 - 9: From from Baseline to Week 56 and Week 80 5 + 10: From from Baseline to Week 80 |
1 - 4: Dal basale al follow-up di sicurezza (Settimana 152) 6 - 9: Dal basale alla Settimana 56 e alla Settimana 80 5 + 10: Dal basale alla Settimana 80 |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability; Immunogenicity |
Tollerabilità; immunogenicità |
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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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Periodo di trattamento in doppio cieco seguito da un periodo di estensione del trattamento in aperto |
Double-blind Treatment Period followed by Open-label Extension Treatment Period |
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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 | 3 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
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 |
United States |
Belgium |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
United Kingdom |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 25 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 25 |