E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease |
|
E.1.1.1 | Medical condition in easily understood language |
Study to evaluate the efficacy, safety, tolerability and pharmacokinetics of various anti-inflammatory agents in patients with early Alzheimer's disease |
|
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 |
|
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 compare the effects of each individual agent vs. placebo on cognition in early AD |
|
E.2.2 | Secondary objectives of the trial |
• To investigate the safety (AEs) and tolerability of each individual agent vs placebo • To investigate the effects of each individual agent vs placebo in lowering central inflammation • To explore the effects of each individual agent vs placebo on neuropsychiatric symptoms • To compare the effects of each individual agent vs placebo on function (activities of daily living) • To compare the effects of each individual agent vs placebo on memory and executive function • To determine the pharmacokinetics of each individual agent • To determine the total target and immunogenicity of each individual biotherapeutic agent
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, age ≥ 45 years and ≤ 90 years at the time of signing the informed consent; 2. Participant has a reliable study partner or caregiver can accompany the participant to all visits; 3. A diagnosis of probable MCI due to AD or mild AD according to the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria; 4. Confirmed amyloid and tau positivity via CSF sampling performed at screening; 5. Mini-Mental State Examination (MMSE) total score of 20 to 30 (inclusive). Participants who score 25 points on MMSE or higher must additionally score at least half a standard deviation (SD) below education adjusted normative data on the DSST at point of screening |
|
E.4 | Principal exclusion criteria |
1. Use of an investigational agent or an approved product with the intent to modulate inflammation or modulate the course of AD (e.g., Tau ASOs, gene therapy, amyloid or tau vaccine): • previous use of small molecules is allowed if discontinued for at least five half-lives, or at least 30 days from when the expected pharmacodynamic effect has returned to baseline, whichever is longer • previous use of monoclonal and polyclonal antibodies or other biologics is allowed if discontinued for at least five half-lives prior to screening 2. Current medical or neurological condition that in the judgement of the investigator might impact cognition or performance on cognitive assessments, e.g., MCI not due to AD, non-Alzheimer dementia, Huntington's disease, Parkinson's disease, stroke, schizophrenia, bipolar disorder, active major depression, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), active seizure disorder, or history of traumatic brain injury associated with loss of consciousness and ongoing residual transient or permanent neurological signs/symptoms including cognitive deficits, and/or associated with skull fracture. 3. Diagnosis of vascular dementia prior to baseline (e.g.., modified Hachinski Ischaemic Scale score > 6 or those who meet the NINDS AIREN criteria for vascular dementia) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• The Neuropsychological Test Battery (NTB) score |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Safety • Positron-Emission Tomography Translocator Protein 18 kDa (PET TSPO) • The Neuropsychiatric Inventory (NPI-D) total score • Tablet-based neuropsychiatric At-Home study partner assessment score • The Everyday Cognition (ECog) scale • The Neuropsychological Test Battery memory and executive function composites • Digit Symbol Substitution Test • Tablet-based cognitive at-home assessment • Pharmacokinetics and pharmacodynamics in plasma and cerebrospinal fluid |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
throughout the 24 week trial |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 |
Immunogenicity and Tolerability |
|
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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
|
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 | 7 |
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 |
United Kingdom |
United States |
Finland |
Iceland |
|
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
|
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | 18 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |