Study of the efficacy and safety of various anti-inflammatory agents in participants with mild cognitive impairment or mild Alzheimer's Disease

Phase 1

Conditions: Mild cognitive impairment due to Alzheimer’s disease and mild Alzheimer’s disease
MedDRA version: 20.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2020-003966-38-FI

Lead Sponsor: ovartis Pharma AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 900

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 720

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)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To compare the effects of each individual agent vs. placebo on cognition in early AD;Secondary Objective: • To investigate the safety (AEs) and tolerability of each individual agent vs placebo <br>• To investigate the effects of each individual agent vs placebo in lowering central inflammation <br>• To explore the effects of each individual agent vs placebo on neuropsychiatric symptoms<br>• To compare the effects of each individual agent vs placebo on function (activities of daily living)<br>• To compare the effects of each individual agent vs placebo on memory and executive function<br>• To determine the pharmacokinetics of each individual agent<br>• To determine the total target and immunogenicity of each individual biotherapeutic agent<br>;Primary end point(s): • The Neuropsychological Test Battery (NTB) score;Timepoint(s) of evaluation of this end point: 24 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Safety<br>• Positron-Emission Tomography Translocator Protein 18 kDa (PET TSPO)<br>• The Neuropsychiatric Inventory (NPI-D) total score <br>• Tablet-based neuropsychiatric At-Home study partner assessment score <br>• The Everyday Cognition (ECog) scale <br>• The Neuropsychological Test Battery memory and executive function composites <br>• Digit Symbol Substitution Test <br>• Tablet-based cognitive at-home assessment<br>• Pharmacokinetics and pharmacodynamics in plasma and cerebrospinal fluid;Timepoint(s) of evaluation of this end point: throughout the 24 week trial

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