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TerminatedPhase 2Results posted

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

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

Asset

Canakinumab

Listed sites

10

Recruiting sites

-

Enrollment

34

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

•MCI due to AD•Amyloid biomarker required (CSF)•Tau biomarker required (CSF)•MMSE 20-24•Study partner/caregiver required

Primary endpoint

•Cognition

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDCADPT06A12201
NCT IDNCT04795466

Timeline

Milestones

Study first posted2021-03-12actual
Study start2021-10-28actual
Primary completion2024-03-07actual
Study completion2024-03-07actual
Results first posted2025-05-06actual
Last update posted2025-10-16actual

Assets

Drug assets

Canakinumab

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age45 Years
Maximum age90 Years
SexAll
Healthy volunteersNot accepted

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);

Endpoints (34)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Memory
8
Global cognition
6
Behavior / neuropsychiatric
6
Safety / tolerability / PK
6
Executive function / language
4
Fluid / digital biomarkers
2
Other (unclassified)
2

Global cognition

6 endpoints
Primary/protocol endpoint

Change From Baseline in Cognition as Measured by the Neuropsychological Test Battery (NTB) Z-scores

Time frame:Baseline and day 171

change from baseline, improvement

Primary/registry result

Change From Baseline in Cognition as Measured by the Neuropsychological Test Battery (NTB) Z-scores

Time frame:Baseline and day 171

change from baseline, improvement

Posted result

GroupValue (least_squares_mean), z-scoreStandard error
Canakinumabn=10 Participants0.2250.116
Placebon=16 Participants0.1560.0905
Least square mean difference0.06990% CI-0.178 - 0.316p0.6386Mixed Models Analysis

NTB Total z-score - day 171

Secondary/protocol endpoint

Change From Baseline in Memory as Measured by the Total Composite NTB Memory Z-score

Time frame:Baseline and day 171

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Executive Function as Measured by the Total Composite NTB Executive Function Z-score

Time frame:Baseline and day 171

change from baseline, improvement

Secondary/registry result

Change From Baseline in Memory as Measured by the Total Composite NTB Memory Z-score

Time frame:Baseline and day 171

change from baseline, improvement

Posted result

GroupValue (least_squares_mean), z-score change from baselineStandard error
Canakinumabn=10 Participants0.4610.1382
Placebon=16 Participants0.4630.1062
Least squares mean difference-0.00290% CI-0.300 - 0.296p0.9917Mixed Models Analysis

Memory function - day 171

Secondary/registry result

Change From Baseline in Executive Function as Measured by the Total Composite NTB Executive Function Z-score

Time frame:Baseline and day 171

change from baseline, improvement

Posted result

GroupValue (least_squares_mean), z-score change from baselineStandard error
Canakinumabn=10 Participants0.1110.1492
Placebon=16 Participants-0.0750.1251
least squares mean difference0.18690% CI-0.148 - 0.520p0.3510Mixed Models Analysis

Executive function- day 171

Memory

8 endpoints
Secondary/protocol endpoint

Change From Baseline in Everyday Cognition Scale (ECog) Total Score

Time frame:Baseline and day 171

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in eCognitive Testing Scores - SWM Between Errors

Time frame:Baseline, day 85

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in eCognitive Testing Scores - SWM Strategy

Time frame:Baseline, day 85

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in eCognitive Testing Scores - PAL First Attempt Memory Score

Time frame:Baseline, day 85

change from baseline, improvement

Secondary/registry result

Change From Baseline in Everyday Cognition Scale (ECog) Total Score

Time frame:Baseline and day 171

change from baseline, improvement

Posted result

GroupValue (mean), ECog total score change from BaselineStandard deviation
Canakinumabn=10 Participants1.214.26
Placebon=16 Participants3.411.79
Secondary/registry result

Change From Baseline in eCognitive Testing Scores - SWM Between Errors

Time frame:Baseline, day 85

change from baseline, improvement

Posted result

GroupValue (mean), SWMBE score change from baselineStandard deviation
Canakinumabn=9 Participants-1.566.018
Placebon=12 Participants-1.834.910
Secondary/registry result

Change From Baseline in eCognitive Testing Scores - SWM Strategy

Time frame:Baseline, day 85

change from baseline, improvement

Posted result

GroupValue (mean), scores on a scaleStandard deviation
Canakinumabn=9 Participants-0.281.149
Placebon=12 Participants-0.921.459
Secondary/registry result

Change From Baseline in eCognitive Testing Scores - PAL First Attempt Memory Score

Time frame:Baseline, day 85

change from baseline, improvement

Posted result

GroupValue (mean), PAL score change from baselineStandard deviation
Canakinumabn=9 Participants-0.172.716
Placebon=12 Participants0.083.059

Executive function / language

4 endpoints
Secondary/protocol endpoint

Change From Baseline in Digit Symbol Substitution Test (DSST) Score - CANTAB

Time frame:Baseline and day 171

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in eCognitive Testing Scores - MTS Proportional Slowing 8-2 Patterns

Time frame:Baseline, day 85

change from baseline, improvement

Secondary/registry result

Change From Baseline in Digit Symbol Substitution Test (DSST) Score - CANTAB

Time frame:Baseline and day 171

change from baseline, improvement

Posted result

GroupValue (least_squares_mean), DSST score change from baselineStandard error
Canakinumabn=10 Participants1.961.37
Placebon=16 Participants2.451.13
Repeated measures analysis-0.4990% CI-3.56 - 2.58p0.7870Mixed Models Analysis

DSST - day 171

Secondary/registry result

Change From Baseline in eCognitive Testing Scores - MTS Proportional Slowing 8-2 Patterns

Time frame:Baseline, day 85

change from baseline, improvement

Posted result

GroupValue (mean), Change from baseline in millisecondsStandard deviation
Canakinumabn=9 Participants143.7802871.0641
Placebon=12 Participants77.5732824.3325

Behavior / neuropsychiatric

6 endpoints
Secondary/protocol endpoint

Change From Baseline in Neuropsychiatric Symptoms as Measured by the Neuropsychiatric Inventory (NPI) Total Score

Time frame:Baseline and day 171

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Neuropsychiatric Symptoms Associated Distress as Measured by the Neuropsychiatric Inventory Caregiver Distress (NPI-D) Score

Time frame:Baseline and day 171

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Mean eNeuropsychiatric at Home Caregiver Assessment Score

Time frame:Baseline, day 85

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/registry result

Change From Baseline in Neuropsychiatric Symptoms as Measured by the Neuropsychiatric Inventory (NPI) Total Score

Time frame:Baseline and day 171

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

GroupValue (mean), NPI total score change from BaselineStandard deviation
Canakinumabn=10 Participants-1.47.76
Placebon=16 Participants2.98.68
Secondary/registry result

Change From Baseline in Neuropsychiatric Symptoms Associated Distress as Measured by the Neuropsychiatric Inventory Caregiver Distress (NPI-D) Score

Time frame:Baseline and day 171

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

GroupValue (mean), NPI-D score change from BaselineStandard deviation
Canakinumabn=10 Participants-2.77.70
Placebon=16 Participants1.25.74
Secondary/registry result

Change From Baseline in Mean eNeuropsychiatric at Home Caregiver Assessment Score

Time frame:Baseline, day 85

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

GroupValue (mean), scores on a scaleStandard deviation
Canakinumabn=10 Participants0.9833.7904
Placebon=12 Participants-1.0941.7083

Fluid / digital biomarkers

2 endpoints
Secondary/protocol endpoint

Total Target (IL-1 Beta) Concentration in Serum and CSF

Time frame:Baseline, day 29, day 57, day 85, day 141, day 171 for serum concentrations and Baseline and day 85 for CSF concentrations

concentration, descriptive

Secondary/registry result

Total Target (IL-1 Beta) Concentration in Serum and CSF

Time frame:Baseline, day 29, day 57, day 85, day 141, day 171 for serum concentrations and Baseline and day 85 for CSF concentrations

concentration, descriptive

Posted result

GroupValue (mean), pg/mLStandard deviation
CanakinumabSerum - Baselinen=13 Participants0.0000.0000
Serum - Day 29n=15 Participants12.6324.4949
Serum - Day 57n=13 Participants20.81810.2918
Serum - Day 85n=11 Participants23.2915.2984
Serum - Day 141n=11 Participants44.47358.3963
Serum - Day 171n=10 Participants28.46018.4483
CSF - Baselinen=15 Participants0.0000.0000
CSF - Day 85n=12 Participants0.0000.0000
PlaceboSerum - Baselinen=18 Participants0.0000.0000
Serum - Day 29n=18 Participants0.0000.0000
Serum - Day 57n=17 Participants0.0000.0000
Serum - Day 85n=16 Participants0.0000.0000
Serum - Day 141n=16 Participants0.0000.0000
Serum - Day 171n=16 Participants0.0000.0000
CSF - Baselinen=18 Participants0.0000.0000
CSF - Day 85n=15 Participants0.0230.0883

Safety / tolerability / PK

6 endpoints
Secondary/protocol endpoint

Serum Pharmacokinetic Concentrations of Canakinumab

Time frame:Baseline, day29, day 57, day 85, day 141, day 171

concentration, descriptive

Secondary/protocol endpoint

Number of Participants With Anti-agent Antibodies in Serum

Time frame:Baseline, day 85, day 171

event count, event

Secondary/protocol endpoint

Number of Participants Who Experience Adverse Events and Serious Adverse Events

Time frame:From first dose up to approximately 140 days post last dose (day 281)

event count, event

Secondary/registry result

Serum Pharmacokinetic Concentrations of Canakinumab

Time frame:Baseline, day29, day 57, day 85, day 141, day 171

concentration, descriptive

Posted result

GroupValue (mean), ng/mLStandard deviation
CanakinumabBaselinen=14 Participants0.00.00
Day 29n=16 Participants8921.32721.47
Day 57n=13 Participants14230.84712.07
Day 85n=12 Participants26575.010216.93
Day 141n=11 Participants34000.011288.67
Day 171n=10 Participants33170.06825.45
Secondary/registry result

Number of Participants With Anti-agent Antibodies in Serum

Time frame:Baseline, day 85, day 171

event count, event

Posted result

GroupValue (count_of_participants), ParticipantsReported bounds
CanakinumabBaseline · POSITIVEn=16 Participants0-
Baseline · NEGATIVEn=16 Participants16-
Day 85 · POSITIVEn=12 Participants0-
Day 85 · NEGATIVEn=12 Participants12-
Day 171 · POSITIVEn=10 Participants0-
Day 171 · NEGATIVEn=10 Participants10-
Secondary/registry result

Number of Participants Who Experience Adverse Events and Serious Adverse Events

Time frame:From first dose up to approximately 140 days post last dose (day 281)

event count, event

Posted result

GroupValue (count_of_participants), ParticipantsReported bounds
CanakinumabParticipants with at least one AEn=16 Participants14-
Participants with grade 1 AEsn=16 Participants14-
Participants with grade 2 AEsn=16 Participants6-
Participants with grade 3 AEsn=16 Participants1-
Participants with study drug related AEsn=16 Participants4-
Participants with serious AEsn=16 Participants2-
Participants with AEs leading to treatment discontinuationn=16 Participants3-
Participants with study drug related AEs leading to treatment discontinuationn=16 Participants1-
PlaceboParticipants with at least one AEn=18 Participants16-
Participants with grade 1 AEsn=18 Participants16-
Participants with grade 2 AEsn=18 Participants6-
Participants with grade 3 AEsn=18 Participants0-
Participants with study drug related AEsn=18 Participants5-
Participants with serious AEsn=18 Participants1-
Participants with AEs leading to treatment discontinuationn=18 Participants1-
Participants with study drug related AEs leading to treatment discontinuationn=18 Participants0-

Other (unclassified)

2 endpoints
Secondary/protocol endpoint/low confidence

Change From Baseline in Microglia Activation as Measured by Positron-Emission Tomography-Translocator Protein 18kDa - Microglia Activation

Time frame:Baseline and day 85

percent change from baseline, improvement

Secondary/registry result/low confidence

Change From Baseline in Microglia Activation as Measured by Positron-Emission Tomography-Translocator Protein 18kDa - Microglia Activation

Time frame:Baseline and day 85

percent change from baseline, improvement

Posted result

GroupValue (mean), Percent change from baselineStandard deviation
Placebon=1 ParticipantsNANA

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 21, 2026
Endpoint classificationDelfa ADRD endpoint taxonomy
Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.