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

Novartis

Status and phase: Terminated; Phase 2

Conditions: Alzheimer Disease; Mild Cognitive Impairment

Treatments: Biological: Canakinumab; Other: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04795466

CADPT06A12201

Details and patient eligibility

About

The purpose of this platform study was to evaluate the effect of anti-inflammatory agents on cognition in early Alzheimer's disease. Additionally, the safety and tolerability and their effects on central and peripheral inflammation were evaluated. Due to early termination only a single agent could be studied.

Full description

This was 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 was originally planned as a platform study, designed to investigate different agents in a continuous manner. However, due to early termination of the study only one experimental arm was enrolled.

The study included a screening period (Day -60 to Day -8), followed by a baseline period of 7 days (Day -7 to Day -1), a treatment period of 20 weeks (Day 1 to Day 141), a study completion evaluation (EOC1) approximately 30 days after the last agent administration (Day 171) and a second end of cohort visit (EOC2) approximately 140 days after the last agent administration (Day 281).

Enrollment: 34 patients

Sex: All

Ages: 45 to 90 years old

Volunteers: No Healthy Volunteers

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.

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;

• 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);

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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34 participants in 2 patient groups, including a placebo group

Canakinumab

Experimental group

Description:

Canakinumab 150 mg SC once every 4 weeks for the first 2 doses followed by 300 mg SC once every 4 weeks for the subsequent 4 doses.

Treatment:

Biological: Canakinumab

Placebo

Placebo Comparator group

Description:

Matching placebo sub-cutaneous injections

Treatment:

Other: Placebo