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Terminated by Sponsor
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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Canakinumab | Experimental | 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. |
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| Placebo | Placebo Comparator | Matching placebo sub-cutaneous injections |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Canakinumab | Biological | Biological subcutaneous injection |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Cognition as Measured by the Neuropsychological Test Battery (NTB) Z-scores | 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. Total Z-score was derived by averaging all 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. | Baseline and day 171 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Memory as Measured by the Total Composite NTB Memory Z-score | 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. |
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Inclusion Criteria:
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):
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);
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Charlestown | Massachusetts | 02129 | United States | ||
| SUNY at Stony Brook |
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| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on www.novctrd.com | View source |
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Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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There was a screening period (Day -60 to Day -8), followed by a baseline period of 7 days (Day -7 to Day -1), before first treatment.
Participants were enrolled at 10 sites in 4 different countries
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| ID | Title | Description |
|---|---|---|
| FG000 | Canakinumab | 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. |
| FG001 | Placebo | Matching placebo subcutaneous injections |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 15, 2022 | Mar 5, 2025 |
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| Placebo | Other | Matching placebo subcutaneous injection |
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| Baseline and day 171 |
| Change From Baseline in Executive Function as Measured by the Total Composite NTB Executive Function Z-score | 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. | Baseline and day 171 |
| Change From Baseline in Digit Symbol Substitution Test (DSST) Score - CANTAB | 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 | Baseline and day 171 |
| Change From Baseline in Neuropsychiatric Symptoms as Measured by the Neuropsychiatric Inventory (NPI) Total Score | 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. | Baseline and day 171 |
| Change From Baseline in Neuropsychiatric Symptoms Associated Distress as Measured by the Neuropsychiatric Inventory Caregiver Distress (NPI-D) Score | 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. | Baseline and day 171 |
| Change From Baseline in Mean eNeuropsychiatric at Home Caregiver Assessment Score | 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 in-clinic NPI assessment and the scores averaged. It ranges from 0 to 144, with higher values indicating greater severity. | Baseline, day 85 |
| Change From Baseline in Everyday Cognition Scale (ECog) Total Score | 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 score is calculated as the sum of all 39 items, and ranges from 0 to 156. Lower total ECog scores indicate better performance. | Baseline and day 171 |
| Change From Baseline in eCognitive Testing Scores - SWM Between Errors | 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 in which a token has previously been found. It starts at 0 without a maximum limit with higher scores indicating a worse outcome. | Baseline, day 85 |
| Change From Baseline in eCognitive Testing Scores - SWM Strategy | 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 same box they started with previously. If they always begin a search from the same starting point, we infer that the subject is employing a planned strategy for finding the tokens. SMW strategy ranges from 3 to 26, a low score indicates high strategy use, they always begin the search from the same box, and a high score indicates that they are beginning their searches from many different boxes. | Baseline, day 85 |
| Change From Baseline in eCognitive Testing Scores - MTS Proportional Slowing 8-2 Patterns | 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 the correct box on their first attempt on the 8 pattern assessment trials compared to the 2 pattern assessment trials. It starts at 0 without a maximum limit, and with higher scores indicating a worse outcome. | Baseline, day 85 |
| Change From Baseline in eCognitive Testing Scores - PAL First Attempt Memory Score | 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. | Baseline, day 85 |
| Change From Baseline in Microglia Activation as Measured by Positron-Emission Tomography-Translocator Protein 18kDa - Microglia Activation | 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. Relative % change from baseline in volume of distribution (Vt) of the radio tracer for TSPO after treatment. Since only one participant completed day 85 PET TSPO, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Baseline and day 85 |
| Serum Pharmacokinetic Concentrations of Canakinumab | Serum pharmacokinetic pre-dose concentrations of CanakinumabConcentrations below the LLOQ were reported as "zero". | Baseline, day29, day 57, day 85, day 141, day 171 |
| Total Target (IL-1 Beta) Concentration in Serum and CSF | Serum and CSF samples were obtained and evaluated for total target concentrations (the sum of free and drug-bound target) as a pharmacodynamic (PD) marker for target engagement. | Baseline, day 29, day 57, day 85, day 141, day 171 for serum concentrations and Baseline and day 85 for CSF concentrations |
| Number of Participants With Anti-agent Antibodies in Serum | Number of participants with anti-agent antibodies in serum. Immunogenicity (IG) was assessed in serum of all participants treated with biotherapeutic drug. | Baseline, day 85, day 171 |
| Number of Participants Who Experience Adverse Events and Serious Adverse Events | Clinically significant abnormalities of laboratory values, physical findings, electrocardiogram findings and other safety assessments were recorded as adverse events if the findings meet the defined criteria for adverse events. AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5. For CTCAE, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE | From first dose up to approximately 140 days post last dose (day 281) |
| Stony Brook |
| New York |
| 11794-8161 |
| United States |
| Novartis Investigative Site | Kuopio | 70210 | Finland |
| Novartis Investigative Site | Turku | 20520 | Finland |
| Novartis Investigative Site | Reykjavik | 101 | Iceland |
| Novartis Investigative Site | Plymouth | Devon | PL6 8BT | United Kingdom |
| Novartis Investigative Site | Guildford | Surrey | GU27YD | United Kingdom |
| Novartis Investigative Site | London | W1G 9JF | United Kingdom |
| Novartis Investigative Site | Motherwell | ML1 4UF | United Kingdom |
| Novartis Investigative Site | Southampton | SO30 3JB | United Kingdom |
| Pharmacodynamic Analysis Set | The pharmacodynamic (PD) analysis set included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Canakinumab | 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. |
| BG001 | Placebo | Matching placebo subcutaneous injections |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Age, Continuous | Median | Full Range | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Cognition as Measured by the Neuropsychological Test Battery (NTB) Z-scores | 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. Total Z-score was derived by averaging all 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. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Least Squares Mean | Standard Error | z-score | Baseline and day 171 |
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| Secondary | Change From Baseline in Memory as Measured by the Total Composite NTB Memory Z-score | 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. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Least Squares Mean | Standard Error | z-score change from baseline | Baseline and day 171 |
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| Secondary | Change From Baseline in Executive Function as Measured by the Total Composite NTB Executive Function Z-score | 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. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Least Squares Mean | Standard Error | z-score change from baseline | Baseline and day 171 |
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| Secondary | Change From Baseline in Digit Symbol Substitution Test (DSST) Score - CANTAB | 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 | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Least Squares Mean | Standard Error | DSST score change from baseline | Baseline and day 171 |
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| Secondary | Change From Baseline in Neuropsychiatric Symptoms as Measured by the Neuropsychiatric Inventory (NPI) Total Score | 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. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Mean | Standard Deviation | NPI total score change from Baseline | Baseline and day 171 |
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| Secondary | Change From Baseline in Neuropsychiatric Symptoms Associated Distress as Measured by the Neuropsychiatric Inventory Caregiver Distress (NPI-D) Score | 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. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Mean | Standard Deviation | NPI-D score change from Baseline | Baseline and day 171 |
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| Secondary | Change From Baseline in Mean eNeuropsychiatric at Home Caregiver Assessment Score | 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 in-clinic NPI assessment and the scores averaged. It ranges from 0 to 144, with higher values indicating greater severity. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Mean | Standard Deviation | scores on a scale | Baseline, day 85 |
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| Secondary | Change From Baseline in Everyday Cognition Scale (ECog) Total Score | 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 score is calculated as the sum of all 39 items, and ranges from 0 to 156. Lower total ECog scores indicate better performance. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Mean | Standard Deviation | ECog total score change from Baseline | Baseline and day 171 |
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| Secondary | Change From Baseline in eCognitive Testing Scores - SWM Between Errors | 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 in which a token has previously been found. It starts at 0 without a maximum limit with higher scores indicating a worse outcome. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Mean | Standard Deviation | SWMBE score change from baseline | Baseline, day 85 |
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| Secondary | Change From Baseline in eCognitive Testing Scores - SWM Strategy | 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 same box they started with previously. If they always begin a search from the same starting point, we infer that the subject is employing a planned strategy for finding the tokens. SMW strategy ranges from 3 to 26, a low score indicates high strategy use, they always begin the search from the same box, and a high score indicates that they are beginning their searches from many different boxes. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Mean | Standard Deviation | scores on a scale | Baseline, day 85 |
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| Secondary | Change From Baseline in eCognitive Testing Scores - MTS Proportional Slowing 8-2 Patterns | 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 the correct box on their first attempt on the 8 pattern assessment trials compared to the 2 pattern assessment trials. It starts at 0 without a maximum limit, and with higher scores indicating a worse outcome. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Mean | Standard Deviation | Change from baseline in milliseconds | Baseline, day 85 |
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| Secondary | Change From Baseline in eCognitive Testing Scores - PAL First Attempt Memory Score | 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. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Mean | Standard Deviation | PAL score change from baseline | Baseline, day 85 |
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| Secondary | Change From Baseline in Microglia Activation as Measured by Positron-Emission Tomography-Translocator Protein 18kDa - Microglia Activation | 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. Relative % change from baseline in volume of distribution (Vt) of the radio tracer for TSPO after treatment. Since only one participant completed day 85 PET TSPO, no data is reported here in order to protect and maintain participant privacy/confidentiality. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. PET TSPO inferential analysis could only be performed if the number of participants with data allowed the analysis without compromising patient privacy/confidentiality. | Posted | Mean | Standard Deviation | Percent change from baseline | Baseline and day 85 |
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| Secondary | Serum Pharmacokinetic Concentrations of Canakinumab | Serum pharmacokinetic pre-dose concentrations of CanakinumabConcentrations below the LLOQ were reported as "zero". | Participants in the pharmacokinetic (PK) analysis set who received Canakinumab. The PK analysis set included all participants with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received any study drug and with no protocol deviations that impact PK data. | Posted | Mean | Standard Deviation | ng/mL | Baseline, day29, day 57, day 85, day 141, day 171 |
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| Secondary | Total Target (IL-1 Beta) Concentration in Serum and CSF | Serum and CSF samples were obtained and evaluated for total target concentrations (the sum of free and drug-bound target) as a pharmacodynamic (PD) marker for target engagement. | Participants in the PD analysis set with an available value for the outcome measure. The PD (total target) analysis set for biotherapeutic agents included all participants with available (total target) PD data and no protocol deviations with relevant impact on (total target) PD data. | Posted | Mean | Standard Deviation | pg/mL | Baseline, day 29, day 57, day 85, day 141, day 171 for serum concentrations and Baseline and day 85 for CSF concentrations |
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| Secondary | Number of Participants With Anti-agent Antibodies in Serum | Number of participants with anti-agent antibodies in serum. Immunogenicity (IG) was assessed in serum of all participants treated with biotherapeutic drug. | Participants in the safety analysis (SA) set who received Canakinumab. The SA set included all participants who received any study drug. | Posted | Count of Participants | Participants | Baseline, day 85, day 171 |
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| Secondary | Number of Participants Who Experience Adverse Events and Serious Adverse Events | Clinically significant abnormalities of laboratory values, physical findings, electrocardiogram findings and other safety assessments were recorded as adverse events if the findings meet the defined criteria for adverse events. AE grades to characterize the severity of the AEs were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5. For CTCAE, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE | The safety analysis set included all participants who received any study drug. | Posted | Count of Participants | Participants | From first dose up to approximately 140 days post last dose (day 281) |
|
|
From first dose up to approximately 140 days post last dose (day 281)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Canakinumab | 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. | 0 | 16 | 2 | 16 | 13 | 16 |
| EG001 | Placebo | Matching placebo subcutaneous injections | 0 | 18 | 1 | 18 | 16 | 18 |
| EG002 | Total | Total | 0 | 34 | 3 | 34 | 29 | 34 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Streptococcal infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Transitional cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (27.0) | Systematic Assessment |
| |
| Metabolic encephalopathy | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Vertigo positional | Ear and labyrinth disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Abdominal hernia | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Abdominal tenderness | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Diverticulum | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Sensitisation | Immune system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Asymptomatic bacteriuria | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Otitis externa | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Vaginal infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (27.0) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Immunisation reaction | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Post lumbar puncture syndrome | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Scratch | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Thermal burn | Injury, poisoning and procedural complications | MedDRA (27.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| White blood cells urine positive | Investigations | MedDRA (27.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Intention tremor | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Ischaemic cerebral infarction | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Agitation | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Irritability | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Persecutory delusion | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Procedural anxiety | Psychiatric disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (27.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | +1 862 778 8300 | Novartis.email@Novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 3, 2024 | Mar 5, 2025 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D000544 | Alzheimer Disease |
| D008569 | Memory Disorders |
| D003704 | Dementia |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010335 | Pathologic Processes |
Not provided
Not provided
| ID | Term |
|---|---|
| C541220 | canakinumab |
Not provided
Not provided
Not provided
| Male |
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| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Units | Counts |
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Units |
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| Counts |
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Placebo |
Matching placebo subcutaneous injections |
|
|
Matching placebo subcutaneous injections
|
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|
Matching placebo subcutaneous injections
|
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