E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild cognitive impairment (MCI) or mild dementia, both of the Alzheimer's type |
Decadimento cognitivo lieve (MCI) o demenza lieve, entrambi del tipo Alzheimer |
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E.1.1.1 | Medical condition in easily understood language |
Early Alzheimer's disease |
Malattia di Alzheimer in fase iniziale |
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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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the effect of semaglutide s.c. 1.0 mg once-weekly versus placebo on central and peripheral inflammation in participants with Alzheimer's disease |
Valutare l’effetto di semaglutide s.c. 1,0 mg una volta alla settimana rispetto al placebo sull’infiammazione centrale e periferica nei partecipanti con malattia di Alzheimer |
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E.2.2 | Secondary objectives of the trial |
- To compare the effects of semaglutide s.c. 1.0 mg once-weekly versus placebo on safety and tolerability in participants with Alzheimer's disease - To evaluate the effects of semaglutide s.c. 1.0 mg once-weekly on safety and tolerability in participants with Alzheimer's disease - To evaluate the steady state pharmacokinetics of semaglutide s.c. 1.0 mg once-weekly in participants with Alzheimer's disease |
-Confrontare gli effetti di semaglutide s.c. 1,0 mg una volta alla settimana rispetto al placebo sulla sicurezza e la tollerabilità in partecipanti con malattia di Alzheimer -Valutare gli effetti di semaglutide s.c. 1,0 mg una volta alla settimana sulla sicurezza e la tollerabilità in partecipanti con malattia di Alzheimer -Valutare la farmacocinetica allo stato di equilibrio di semaglutide s.c. 1,0 mg una volta alla settimana in partecipanti con malattia di Alzheimer |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, aged 55-75 years (both inclusive) at the time of signingthe informed consent. - MCI or mild dementia of the Alzheimer's type according to the NIA-AA2018 criteria. - Clinical dementia rating (CDR) global score of 0.5 or 1 at screening (visit 1). - Amyloid positivity established with either historical amyloid positron emission tomography (PET) or historical CSF Aß1-42 or historical CSF Aß1-42/Aß1-40 (historical data within the last 5 years) or blood sample for amyloid biomarker (Aß42/Aß40 ratio and p-tau217/np-tau217 ratio) at screening (visit 1). - Treated with acetylcholinesterase inhibitors (approved for the treatment of Alzheimer's disease) and on stable dose for > 90 days before screening (visit 1). |
-Soggetti di sesso maschile o femminile, età 55-75 anni (estremi compresi) al momento della firma del modulo di consenso informato. -MCI o demenza lieve del tipo di Alzheimer secondo i criteri NIA-AA 2018. -Punteggio CDR globale pari a 0,5 o 1 allo screening (Visita 1). -Positività all’amiloide stabilita mediante scansione anamnestica di tomografia ad emissioni di positroni (PET) dell’amiloide o test anamnestico di Aß1-42 nell’LCS o di Aß1-42/Aß1-40 nell’LCS (dati anamnestici riferiti agli ultimi 5 anni) o campione di sangue per i biomarcatori dell’amiloide (rapporto Aß42/Aß40 e rapporto p-tau217/np-tau217) allo screening (Visita 1). -Trattamento con inibitori dell’acetilcolinesterasi (approvati per il trattamento della malattia di Alzheimer) e a dose stabile per >90 giorni prima dello screening (Visita 1). |
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E.4 | Principal exclusion criteria |
- Brain magnetic resonance imaging (MRI) scan suggestive of clinically significant structural central nervous system (CNS) disease confirmed by local read (e.g., cerebral large-vessel disease [large vessel (cortical) infarcts >10 mm in diameter], prior macro-haemorrhage [>1 cm^3], cerebral vascular malformations, cortical hemosiderosis, intracranial aneurism(s), intracranial tumours, changes suggestive of normal pressure hydrocephalus). - Brain MRI scan suggestive of significant small vessel pathology confirmed by local read and defined as >1 lacunar infarct and/or white matter hyperintensity (WMH) Fazekas scale >2, (WM >20 mm) in the deep white matter and periventricular regions. - History or evidence of autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, lupus, glomerulonephritis, psoriasis (but not limited to): any other medical condition that would require use of systemic corticosteroids or immunosuppressants or immunostimulants in the 12 months prior to screening (visit 1) - Received a vaccine product (including booster) 4 weeks prior to screening (visit 1) or expected to receive a vaccine product (including booster) before visit 5. - Use of any systemic immunomodulating drugs (small molecules and/or biologics) in the last 12 months prior to screening (visit 1) or anticipated use of such drugs during study intervention period 1 (i.e., during the first 12 weeks of treatment until visit 5), such as corticosteroids for systemic use, immunostimulants and immunosuppressants. |
-Risonanza Magnetica (MRI) cerebrale che suggerisce una malattia strutturale clinicamente significativa del Sistema nervoso centrale (SNC) confermata mediante lettura locale (per es. malattia cerebrale dei grandi vasi [infarti dei grandi vasi (corticali) >10 mm di diametro], precedente macro-emorragia [>1 cm³], malformazioni vascolari cerebrali, emosiderosi corticale, aneurisma/i intracranico/i, tumori intracranici, alterazioni indicative di idrocefalo a pressione normale). -MRI cerebrale che suggerisce una patologia significativa dei piccoli vasi confermata mediante lettura locale e definita come >1 infarto lacunare e/o iperintensità della sostanza bianca (WMH) sulla scala Fazekas13 >2, (WM >20 mm) nella sostanza bianca profonda e nelle regioni periventricolari. -Anamnesi o evidenza di malattie autoimmuni come malattia infiammatoria intestinale, artrite reumatoide, lupus, glomerulonefrite, psoriasi (a titolo esemplificativo ma non esaustivo): qualsiasi altra condizione medica che richieda l’uso di corticosteroidi sistemici oppure di immunosoppressori o immunostimolanti nei 12 mesi precedenti lo screening (Visita 1). -Trattamento con un prodotto vaccinale (incluso il richiamo) 4 settimane prima dello screening (Visita 1) o somministrazione prevista di un prodotto vaccinale (incluso il richiamo) prima della Visita 5. -Uso di qualsiasi farmaco immunomodulante sistemico (micromolecole e/o farmaci biologici) negli ultimi 12 mesi prima dello screening (Visita 1) o uso previsto di tali farmaci durante il periodo di trattamento dello studio 1 (ovvero, durante le prime 12 settimane di trattamento fino alla Visita 5) come corticosteroidi per uso sistemico, immunostimolanti e immunosoppressori. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Co-primary: - Change in gene expression assessed by scRNAseq (cells in CSF) - Change in gene expression assessed by scRNAseq (cells in blood) |
Co-primari: -Variazione nell’espressione genica valutata mediante scRNAseq (cellule nel Liquido Cerebrospinale - CSF) -Variazione nell’espressione genica valutata mediante scRNAseq (cellule nel sangue) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From baseline (week 0) to visit 5 (week 12) |
Dal basale (settimana 0) alla Visita 5 (settimana 12) |
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E.5.2 | Secondary end point(s) |
1. Number of treatment emergent adverse events (TEAEs) 2. Number of treatment emergent adverse events (TEAEs) 3. Weekly average semaglutide concentration (Cavg) based on population PK analysis |
-Numero di eventi avversi emergenti dal trattamento (TEAE) -Numero di eventi avversi emergenti dal trattamento (TEAE) -Concentrazione media settimanale di semaglutide (Cmedia) in base all’analisi farmacocinetica (PK) di popolazione. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From baseline (week 0) to visit 5 (week 12) 2. From baseline (week 0) to end of treatment (week 64) 3. From visit 3 (week 4) to end of treatment (week 64) |
-Dal basale (settimana 0) alla Visita 5 (settimana 12) -Dal basale (settimana 0) a fine trattamento (settimana 64) -Dalla Visita 3 (settimana 4) a fine trattamento (settimana 64) |
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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 | 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 | 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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 |
Switzerland |
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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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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 | 1 |
E.8.9.1 | In the Member State concerned days | 22 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 22 |