Clinical trial NCT04795466: Study of the Efficacy and Safety of Various Anti-inflammatory Agents in Participants With Mild Cognitive Impairment or Mild Alzheimer's Disease
Official title: Exploratory PLatform Trial on Anti-Inflammatory Agents in Alzheimer's Disease (EXPLAIN-AD): A Randomized, Placebo-controlled, Multicenter Platform Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Various Anti-inflammatory Agents in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease and Mild Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Mild Cognitive Impairment
Alzheimer Disease
Keywords: Alzheimer disease
Mild Cognitive Impairment
Elderly adults
Adults
Memory loss
Dementia
Inflammation
ADPT06
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-03-12
Enrollment: 34
Sex: ALL
Minimum age (years): 45
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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).

Eligibility criteria: 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);

Primary outcomes:
measure: Change From Baseline in Cognition as Measured by the Neuropsychological Test Battery (NTB) Z-scores
timeFrame: Baseline and day 171
Secondary outcomes:
measure: Change From Baseline in Memory as Measured by the Total Composite NTB Memory Z-score
timeFrame: Baseline and day 171
measure: Change From Baseline in Executive Function as Measured by the Total Composite NTB Executive Function Z-score
timeFrame: Baseline and day 171
measure: Change From Baseline in Digit Symbol Substitution Test (DSST) Score - CANTAB
timeFrame: Baseline and day 171
measure: Change From Baseline in Neuropsychiatric Symptoms as Measured by the Neuropsychiatric Inventory (NPI) Total Score
timeFrame: Baseline and day 171
measure: Change From Baseline in Neuropsychiatric Symptoms Associated Distress as Measured by the Neuropsychiatric Inventory Caregiver Distress (NPI-D) Score
timeFrame: Baseline and day 171
measure: Change From Baseline in Mean eNeuropsychiatric at Home Caregiver Assessment Score
timeFrame: Baseline, day 85
measure: Change From Baseline in Everyday Cognition Scale (ECog) Total Score
timeFrame: Baseline and day 171
measure: Change From Baseline in eCognitive Testing Scores - SWM Between Errors
timeFrame: Baseline, day 85
measure: Change From Baseline in eCognitive Testing Scores - SWM Strategy
timeFrame: Baseline, day 85
measure: Change From Baseline in eCognitive Testing Scores - MTS Proportional Slowing 8-2 Patterns
timeFrame: Baseline, day 85
measure: Change From Baseline in eCognitive Testing Scores - PAL First Attempt Memory Score
timeFrame: Baseline, day 85
measure: Change From Baseline in Microglia Activation as Measured by Positron-Emission Tomography-Translocator Protein 18kDa - Microglia Activation
timeFrame: Baseline and day 85
measure: Serum Pharmacokinetic Concentrations of Canakinumab
timeFrame: Baseline, day29, day 57, day 85, day 141, day 171
measure: Total Target (IL-1 Beta) Concentration in Serum and CSF
timeFrame: Baseline, day 29, day 57, day 85, day 141, day 171 for serum concentrations and Baseline and day 85 for CSF concentrations
measure: Number of Participants With Anti-agent Antibodies in Serum
timeFrame: Baseline, day 85, day 171
measure: Number of Participants Who Experience Adverse Events and Serious Adverse Events
timeFrame: From first dose up to approximately 140 days post last dose (day 281)
Other outcomes:
Locations:
city: Charlestown
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Stony Brook
country: United States
facility: SUNY at Stony Brook
state: New York
city: Kuopio
country: Finland
facility: Novartis Investigative Site
city: Turku
country: Finland
facility: Novartis Investigative Site
city: Reykjavik
country: Iceland
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
state: Devon
city: Guildford
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Motherwell
country: United Kingdom
facility: Novartis Investigative Site
city: Southampton
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
References: