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NCT04795466

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

Terminated Phase 2 Results posted Last updated 16 October 2025
What this trial tests

Phase 2 trial testing Canakinumab in Mild Cognitive Impairment in 34 participants. Terminated before completion.

Timeline
28 October 2021
Primary endpoint
7 March 2024
7 March 2024

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment34
Start date28 October 2021
Primary completion7 March 2024
Estimated completion7 March 2024
Sites10 locations across United Kingdom, Finland, United States, Iceland

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 45 to 90, any sex, with Mild Cognitive Impairment or Alzheimer Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Cognition as Measured by the Neuropsychological Test Battery (NTB) Z-scores Primary · Baseline and day 171

NTB is a composite of multiple neuropsychological tests that provide a thorough assessment of the cognitive domains affected by early Alzheimer's Disease (AD), in particular, memory, executive function, attention and verbal fluency. 5 out of 9 NTB components were administered in the study, Rey Auditory Verbal Learning Test (RAVLT) immediate and delayed scores, Wechsler Memory Scale Digit Span, Controlled Word Association Test (COWAT) and Category Fluency Test (CFT). For each component a raw score was converted to z-score that indicates the number of standard deviations away from the mean. Tot

GroupValue95% CI
Canakinumab0.225± 0.116
Placebo0.156± 0.0905
Change From Baseline in Memory as Measured by the Total Composite NTB Memory Z-score Secondary · Baseline and day 171

Total Neuropsychological Test Battery memory composite score is a "memory function" score composed of the NTB RAVLT immediate and delayed scores. For each component a raw score was converted to z-score that indicates the number of standard deviations away from the mean. Total Z-score was derived by averaging the two resulting z-scores. A change from baseline was calculated as post-baseline z-score minus pre-treatment z-score. A zero Z-score means no cognitive change, a negative value indicates decline, and a positive value means improvement.

GroupValue95% CI
Canakinumab0.461± 0.1382
Placebo0.463± 0.1062
Change From Baseline in Executive Function as Measured by the Total Composite NTB Executive Function Z-score Secondary · Baseline and day 171

The total Neuropsychological Test Battery executive function composite score is an "executive function" score composed of the NTB Wechsler Memory Scale Digit Span, COWAT, and CFT. For each component a raw score was converted to z-score that indicates the number of standard deviations away from the mean. Total Z-score was derived by averaging the two resulting z-scores. A change from baseline was calculated as post-baseline z-score minus pre-treatment z-score. A zero Z-score means no cognitive change, a negative value indicates decline, and a positive value means improvement.

GroupValue95% CI
Canakinumab0.111± 0.1492
Placebo-0.075± 0.1251
Change From Baseline in Digit Symbol Substitution Test (DSST) Score - CANTAB Secondary · Baseline and day 171

The DSST is an attention-demanding component of the Wechsler Adult Intelligence Scale-IV. The DSST score is the number of digits coded correctly in a fixed amount of time. The DSST has a minimum of "0" correct responses and does not have a maximum; a higher number on the DSST represents better performance The test was administered using CANTAB web based testing

GroupValue95% CI
Canakinumab1.96± 1.37
Placebo2.45± 1.13
Change From Baseline in Neuropsychiatric Symptoms as Measured by the Neuropsychiatric Inventory (NPI) Total Score Secondary · Baseline and day 171

Neuropsychiatric Inventory (NPI) total score is globally recognized and the most frequently used assessment of neuropsychiatric symptoms in AD trials. NPI covers twelve neuropsychiatric domains. For each domain there are four scores, frequency (rated 1-4), severity (rated 1-3), domain total score (frequency x severity) and caregiver distress score (rated 0-5). The NPI total score was calculated by adding 12 domain total scores together, and ranges from 0 to 144, with higher values indicating greater severity.

GroupValue95% CI
Canakinumab-1.4± 7.76
Placebo2.9± 8.68
Change From Baseline in Neuropsychiatric Symptoms Associated Distress as Measured by the Neuropsychiatric Inventory Caregiver Distress (NPI-D) Score Secondary · Baseline and day 171

Neuropsychiatric Inventory (NPI) total score is globally recognized and the most frequently used assessment of neuropsychiatric symptoms in AD trials. NPI covers twelve neuropsychiatric domains. For each domain there are four scores, frequency (rated 1-4), severity (rated 1-3), domain total score (frequency x severity) and caregiver distress score (rated 0-5). The caregiver distress score (NPI-D) was calculated by adding together the scores of the 12 individual NPI distress questions, and ranges from 0 to 60, with higher values indicating greater severity.

GroupValue95% CI
Canakinumab-2.7± 7.70
Placebo1.2± 5.74
Change From Baseline in Mean eNeuropsychiatric at Home Caregiver Assessment Score Secondary · Baseline, day 85

Neuropsychiatric Inventory (NPI) total score is globally recognized and the most frequently used assessment of neuropsychiatric symptoms in AD trials. NPI covers twelve neuropsychiatric domains. For each domain there are four scores, frequency (rated 1-4), severity (rated 1-3), domain total score (frequency x severity) and caregiver distress score (rated 0-5). The eNeuropsychiatric at-home assessment was calculated the same way as the in-clinic NPI by adding the12 domain total scores together. The eNeuropsychiatric at-home assessments were completed more frequently than the single time-point

GroupValue95% CI
Canakinumab0.983± 3.7904
Placebo-1.094± 1.7083
Change From Baseline in Everyday Cognition Scale (ECog) Total Score Secondary · Baseline and day 171

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. Each item is scored on a 4 point scale (1=better or no change compared to 10 years earlier, 2=questionable/occasionally worse, 3=consistently a little worse, 4=consistently much worse). An "I don't know" response is also included, in that case the item is not included in the calculation. The total ECog

GroupValue95% CI
Canakinumab1.2± 14.26
Placebo3.4± 11.79
Change From Baseline in eCognitive Testing Scores - SWM Between Errors Secondary · Baseline, day 85

Spatial Working Memory (SWM) is a test of the subject's ability to retain spatial information and to manipulate remembered items in working memory. A trial begins with several colored squares (boxes) being shown on the screen. The overall aim is that the subject should find a blue 'token' in each of the boxes and use them to fill up an empty column. The subject must touch each box in turn until one opens with a blue 'token' inside (a search). Returning to an empty box already sampled on this search is an error. SWM between errors is the number of times the subject incorrectly revisits a box i

GroupValue95% CI
Canakinumab-1.56± 6.018
Placebo-1.83± 4.910
Change From Baseline in eCognitive Testing Scores - SWM Strategy Secondary · Baseline, day 85

Spatial Working Memory (SWM) is a test of the subject's ability to retain spatial information and to manipulate remembered items in working memory. A trial begins with several colored squares (boxes) being shown on the screen. The overall aim is that the subject should find a blue 'token' in each of the boxes and use them to fill up an empty column. The subject must touch each box in turn until one opens with a blue 'token' inside (a search). Returning to an empty box already sampled on this search is an error. SWM Strategy is the number of times a subject begins a new search pattern from the

GroupValue95% CI
Canakinumab-0.28± 1.149
Placebo-0.92± 1.459
Change From Baseline in eCognitive Testing Scores - MTS Proportional Slowing 8-2 Patterns Secondary · Baseline, day 85

Match to Sample Visual Search (MTS) assesses attention and visual searching, with a speed accuracy trade-off. The participant is shown a complex visual pattern in the middle of the screen. After a brief delay, a varying number of similar patterns are shown in a circle of boxes around the edge of the screen. Only one of these patterns matches the pattern in the center of the screen, and the participant must indicate which it is by selecting it. MTS proportional slowing 8-2 patterns is the difference in mean time between presentation of the response stimulus options and the subject selecting th

GroupValue95% CI
Canakinumab143.780± 2871.0641
Placebo77.573± 2824.3325
Change From Baseline in eCognitive Testing Scores - PAL First Attempt Memory Score Secondary · Baseline, day 85

Pair associated learning (PAL): tests participants' visual memory/new learning using patterns randomly displayed in boxes on a screen. Participants are to touch the box where patterns first appeared. PAL first attempt memory score is the number of times a subject choses the correct box on their first attempt when recalling the pattern locations. Ranges from 0 to 20 with higher score indicates a better outcome.

GroupValue95% CI
Canakinumab-0.17± 2.716
Placebo0.08± 3.059

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose up to approximately 140 days post last dose (day 281). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Canakinumab
Serious: 2/16 (13%)
Deaths: 0/16
Placebo
Serious: 1/18 (6%)
Deaths: 0/18
Total
Serious: 3/34 (9%)
Deaths: 0/34

Serious adverse events (4 terms)

ReactionSystemCanakinumabPlaceboTotal
COVID-19Infections and infestations
Streptococcal infectionInfections and infestations
Transitional cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Metabolic encephalopathyNervous system disorders
Other adverse events (62 terms — click to expand)

ReactionSystemCanakinumabPlaceboTotal
HypertensionVascular disorders
Back painMusculoskeletal and connective tissue disorders
Urinary tract infectionInfections and infestations
Blood creatinine increasedInvestigations
Lipase increasedInvestigations
ProteinuriaRenal and urinary disorders
Abdominal painGastrointestinal disorders
Lower respiratory tract infectionInfections and infestations
Upper respiratory tract infectionInfections and infestations
DizzinessNervous system disorders
Confusional statePsychiatric disorders
LymphopeniaBlood and lymphatic system disorders
Vertigo positionalEar and labyrinth disorders
CataractEye disorders
Abdominal herniaGastrointestinal disorders
Abdominal tendernessGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
DiverticulumGastrointestinal disorders
DyspepsiaGastrointestinal disorders
HaemorrhoidsGastrointestinal disorders
Inguinal herniaGastrointestinal disorders
PancreatitisGastrointestinal disorders
SensitisationImmune system disorders
Asymptomatic bacteriuriaInfections and infestations
ConjunctivitisInfections and infestations
Otitis externaInfections and infestations
PneumoniaInfections and infestations
Respiratory tract infectionInfections and infestations
RhinitisInfections and infestations
TonsillitisInfections and infestations
Vaginal infectionInfections and infestations
Viral infectionInfections and infestations
Viral upper respiratory tract infectionInfections and infestations
ContusionInjury, poisoning and procedural complications
FallInjury, poisoning and procedural complications
Immunisation reactionInjury, poisoning and procedural complications
Post lumbar puncture syndromeInjury, poisoning and procedural complications
ScratchInjury, poisoning and procedural complications
Thermal burnInjury, poisoning and procedural complications
Alanine aminotransferase increasedInvestigations

Most-reported serious reactions: COVID-19, Streptococcal infection, Transitional cell carcinoma, Metabolic encephalopathy.

Data from ClinicalTrials.gov NCT04795466 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Microglia in Neuroinflammation and Neurodegeneration: From Understanding to Therapy.
    Muzio L, Viotti A, Martino G. · · 2021 · cited 413× · PMID 34630027 · DOI 10.3389/fnins.2021.742065
  2. Alzheimer's disease drug development pipeline: 2022.
    Cummings J, Lee G, Nahed P, Kambar MEZN, et al · · 2022 · cited 369× · PMID 35516416 · DOI 10.1002/trc2.12295
  3. Alzheimer's disease drug development pipeline: 2023.
    Cummings J, Zhou Y, Lee G, Zhong K, et al · · 2023 · cited 326× · PMID 37251912 · DOI 10.1002/trc2.12385
  4. Alzheimer's disease drug development pipeline: 2024.
    Cummings J, Zhou Y, Lee G, Zhong K, et al · · 2024 · cited 209× · PMID 38659717 · DOI 10.1002/trc2.12465
  5. The Link between Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation in the Pathophysiology of Alzheimer's Disease: Therapeutic Implications and Future Perspectives.
    Jurcău MC, Andronie-Cioara FL, Jurcău A, Marcu F, et al · · 2022 · cited 119× · PMID 36358538 · DOI 10.3390/antiox11112167
  6. Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer's Disease Progression.
    Andronie-Cioara FL, Ardelean AI, Nistor-Cseppento CD, Jurcau A, et al · · 2023 · cited 109× · PMID 36768235 · DOI 10.3390/ijms24031869
  7. Alzheimer's and Parkinson's disease therapies in the clinic.
    Chopade P, Chopade N, Zhao Z, Mitragotri S, et al · · 2023 · cited 96× · PMID 36684083 · DOI 10.1002/btm2.10367
  8. Alzheimer's Disease: Novel Targets and Investigational Drugs for Disease Modification.
    Cummings JL, Osse AML, Kinney JW. · · 2023 · cited 75× · PMID 37728864 · DOI 10.1007/s40265-023-01938-w

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Other trials of Canakinumab

Trials testing the same drug.

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04795466.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing