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 |
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E.1.1.1 | Medical condition in easily understood language |
Early Alzheimer's disease |
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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 |
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 |
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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 |
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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 signing the informed consent. - MCI or mild dementia of the Alzheimer’s type according to the NIA-AA 2018 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 Aβ1-42 or historical CSF Aβ1-42/Aβ1-40 (historical data within the last 5 years) or blood sample for amyloid biomarker (Aβ42/Aβ40 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). |
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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): o 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. |
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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) |
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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) |
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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 |
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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) |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | No |
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 |
European Union |
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 |