Study of the Efficacy and Safety of Various Anti-inflammatory Agents in Participants With Mild Cognitive Impairment or Mild Alzheimer's Disease

Phase 2

Terminated

• Conditions: Mild Cognitive Impairment; Alzheimer Disease
• Interventions: Other: Placebo; Biological: Canakinumab

• Registration Number: NCT04795466
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

The purpose of this platform study is to evaluate the effect of anti-inflammatory agents on cognition in early Alzheimer's disease. Additionally, the safety and tolerability of these anti-inflammatory agents and the effects on central and peripheral inflammation will be evaluated.

Detailed Description

This is a randomized, placebo-controlled, participant- and investigator-blinded study in participants with either mild cognitive impairment or mild Alzheimer's disease with evidence of peripheral inflammation. This study is using a platform design to be able to investigate different agents (therapies) in a perpetual manner. Each unique investigational agent will have a unique cohort of participants assigned. New cohorts of participants may be enrolled to investigate additional agents at unspecified timepoints throughout the study.

There are three periods in the study: screening period of 60 days that includes a baseline period of 7 days, a treatment period (20 weeks) and a follow-up period (28 days) and an additional follow-up visit for therapies with a longer washout.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2021-03-10
• Study First Submitted QC: 2021-03-10
• Study First Posted: 2021-03-12
• Study Start: 2021-10-28
• Primary Completion: 2024-03-07
• Study Completion: 2024-03-07
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-23
• Last Update Posted: 2024-12-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• Male or female, age ≥ 45 years and ≤ 90 years at the time of signing the informed consent;
• Participant has a reliable study partner or caregiver can accompany the participant to all visits;
• 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;
• Confirmed amyloid and tau positivity via CSF sampling performed at screening;
• Mini-Mental State Examination (MMSE) total score of 20 to 24 (inclusive) at screening; OR, MMSE total score of 25-30 (inclusive) plus a DSST score at least 0.5 standard deviation (SD) below normative data at screening.

Read More

Exclusion Criteria

• 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 prior to screening, whichever is longer
  • Previous use of monoclonal or polyclonal antibodies or other biologics is allowed if discontinued for at least five half-lives prior to screening

• 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;

• 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);

• 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);

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo sub-cutaneous injections
Canakinumab	Canakinumab	increasing doses of sub-cutaneous injections

Primary Outcome Measures

Name	Time	Method
Change from baseline in cognition as measured by the Neuropsychological Test Battery (NTB) total score	Baseline and at 24 weeks	Neuropsychological Test Battery (NTB) is a composite of multiple globally-established neuropsychological tests that parovide a thorough assessment of the cognitive domains affect by early Alzheimer's Disease (AD), in particular, memory, executive function, attention and verbal fluency.

Secondary Outcome Measures

Name	Time	Method
Change from baseline in neuropsychiatric symptoms as measured by the Neuropsychiatric Inventory (NPI) total score	Baseline and at 24 weeks	Neuropsychiatric Inventory (NPI) total score is a globally recognized and the most frequently used assessment of neuropsychiatric symptoms in AD trials that covers twelve neuropsychiatric domains.
Change from baseline in pharmacokinetic concentrations and immunogenetic anti-agent antibody levels in serum and/or plasma and/or cerebrospinal fluid	Baseline through to 24 weeks	Pharmacokinetic concentrations and Immunogenic anti-agent antibodies that are measured to assess how the study agent is transported around the body in the blood and CSF and if antibodies are produced by the body in response to the study agent.
Number of participants who experience adverse events and serious adverse events	Baseline up to 30 days post last dose	Clinically significant abnormalities of laboratory values, physical findings, electrocardiogram findings and other safety assessments will be recorded as adverse events if the findings meet the defined criteria for adverse events.
Change from baseline in microglia activation as measured by Positron-Emission Tomography-Translocator Protein 18kDa - microglia activation	Baseline and at 12 weeks	Positron-Emission Tomography-Translocator Protein 18kDa-microglia activation (PET TSPO) is considered a marker of central inflammation (a marker for activated microglia and astrocytes) and the signal strength has been shown to correlate with worsening clinical severity in participants with MCI or AD, measures of cognition and various clinical scores.
Change from baseline in function (activities of daily living) as measured by the Everyday Cognition (eCog) total score	Baseline and at 24 weeks	Everyday Cognition (eCog) scale measures cognitively-relevant everyday abilities and is comprised of 39 items covering six cognitively-relevant domains: Everyday Memory, Everyday Language, Everyday Visuospatial Abilities, Everyday Planning, Everyday Organization, and Everyday Divided Attention.
Change from baseline in memory as measured by the total Neuropsychological Test Battery memory composite score and change from baseline in executive function as measured by the total Neuropsychological Test Battery executive function composite score	Baseline and at 24 weeks	Total Neuropsychological Test Battery memory composite score is a "memory function" composite score and is obtained by averaging the following z-scores from the NTB: RAVLT immediate and delayed scores. The total Neuropsychological Test Battery executive function composite score is an "executive function" composite score that is obtained by averaging the following three z-scores from the NTB: Wechsler Memory Scale Digit Span, COWAT, and CFT.

Trial Locations

Locations (3)

Massachusetts General Hospital; 🇺🇸 Charlestown, Massachusetts, United States

SUNY at Stony Brook; 🇺🇸 Stony Brook, New York, United States

Novartis Investigative Site; 🇬🇧 Southampton, United Kingdom