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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: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Registration Number
EUCTR2020-003966-38-IS
Lead Sponsor
ovartis Pharma AG
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
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) and DSST score at least one standard deviation (SD) below normative data 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 other investigational agents prior to screening until:a) Small molecules: after five half-lives, or within 30 days until the expected pharmacodynamic effect has returned to baseline, whichever is longer; OR b) Biologicals: blood concentration has returned to baseline (or below serological responder threshold) for antibodies induced by active immunotherapy; or five half-lives for monoclonal antibodies or other biologicals;
2. Current medical or neurological condition that 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. If a historical MRI or CT scan has been performed, signs of major cerebrovascular disease shown on such scans (i.e., presence of infarction in greater than 25% of white matter; more than one lacune within basal ganglia or more than 2 lacunes in white matter);
4. Diagnosis of vascular dementia prior to screening (e.g.., modified Hachinski Ischaemic Scale score > 6 or those who meet the NINDS AIREN criteria for vascular dementia);
5. Previous exposure to amyloid vaccines or intravenous immunoglobulins meant to treat Alzheimer's disease.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
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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