Trial Outcomes & Findings for Study of the Efficacy and Safety of Various Anti-inflammatory Agents in Participants With Mild Cognitive Impairment or Mild Alzheimer's Disease (NCT NCT04795466)

Last Updated: 2025-10-16

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

34 participants

Primary outcome timeframe

Baseline and day 171

Results posted on

2025-10-16

Participant Flow

Participants were enrolled at 10 sites in 4 different countries

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.

Participant milestones

Participant milestones
Measure	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.	Placebo Matching placebo subcutaneous injections
Overall Study STARTED	16	18
Overall Study Pharmacodynamic Analysis Set	15	18
Overall Study COMPLETED	10	16
Overall Study NOT COMPLETED	6	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Placebo Matching placebo subcutaneous injections
Overall Study Adverse Event	3	1
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Canakinumab n=16 Participants 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.	Placebo n=18 Participants Matching placebo subcutaneous injections	Total n=34 Participants Total of all reporting groups
Age, Continuous	71.5 Years n=5 Participants	73.5 Years n=7 Participants	72 Years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	8 Participants n=7 Participants	11 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	10 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	18 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	18 Participants n=7 Participants	34 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and day 171

Outcome measures

Outcome measures
Measure	Canakinumab n=10 Participants 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.	Placebo n=16 Participants Matching placebo subcutaneous injections
Change From Baseline in Cognition as Measured by the Neuropsychological Test Battery (NTB) Z-scores	0.225 z-score Standard Error 0.116	0.156 z-score Standard Error 0.0905

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Canakinumab n=10 Participants 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.	Placebo n=16 Participants Matching placebo subcutaneous injections
Change From Baseline in Memory as Measured by the Total Composite NTB Memory Z-score	0.461 z-score change from baseline Standard Error 0.1382	0.463 z-score change from baseline Standard Error 0.1062

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Canakinumab n=10 Participants 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.	Placebo n=16 Participants Matching placebo subcutaneous injections
Change From Baseline in Executive Function as Measured by the Total Composite NTB Executive Function Z-score	0.111 z-score change from baseline Standard Error 0.1492	-0.075 z-score change from baseline Standard Error 0.1251

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Canakinumab n=10 Participants 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.	Placebo n=16 Participants Matching placebo subcutaneous injections
Change From Baseline in Digit Symbol Substitution Test (DSST) Score - CANTAB	1.96 DSST score change from baseline Standard Error 1.37	2.45 DSST score change from baseline Standard Error 1.13

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Canakinumab n=10 Participants 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.	Placebo n=16 Participants Matching placebo subcutaneous injections
Change From Baseline in Neuropsychiatric Symptoms as Measured by the Neuropsychiatric Inventory (NPI) Total Score	-1.4 NPI total score change from Baseline Standard Deviation 7.76	2.9 NPI total score change from Baseline Standard Deviation 8.68

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Canakinumab n=10 Participants 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.	Placebo n=16 Participants Matching placebo subcutaneous injections
Change From Baseline in Neuropsychiatric Symptoms Associated Distress as Measured by the Neuropsychiatric Inventory Caregiver Distress (NPI-D) Score	-2.7 NPI-D score change from Baseline Standard Deviation 7.70	1.2 NPI-D score change from Baseline Standard Deviation 5.74

SECONDARY outcome

Timeframe: 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 in-clinic NPI assessment and the scores averaged. It ranges from 0 to 144, with higher values indicating greater severity.

Outcome measures

Outcome measures
Measure	Canakinumab n=10 Participants 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.	Placebo n=12 Participants Matching placebo subcutaneous injections
Change From Baseline in Mean eNeuropsychiatric at Home Caregiver Assessment Score	0.983 scores on a scale Standard Deviation 3.7904	-1.094 scores on a scale Standard Deviation 1.7083

SECONDARY outcome

Timeframe: 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 score is calculated as the sum of all 39 items, and ranges from 0 to 156. Lower total ECog scores indicate better performance.

Outcome measures

Outcome measures
Measure	Canakinumab n=10 Participants 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.	Placebo n=16 Participants Matching placebo subcutaneous injections
Change From Baseline in Everyday Cognition Scale (ECog) Total Score	1.2 ECog total score change from Baseline Standard Deviation 14.26	3.4 ECog total score change from Baseline Standard Deviation 11.79

SECONDARY outcome

Timeframe: 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 in which a token has previously been found. It starts at 0 without a maximum limit with higher scores indicating a worse outcome.

Outcome measures

Outcome measures
Measure	Canakinumab n=9 Participants 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.	Placebo n=12 Participants Matching placebo subcutaneous injections
Change From Baseline in eCognitive Testing Scores - SWM Between Errors	-1.56 SWMBE score change from baseline Standard Deviation 6.018	-1.83 SWMBE score change from baseline Standard Deviation 4.910

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Canakinumab n=9 Participants 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.	Placebo n=12 Participants Matching placebo subcutaneous injections
Change From Baseline in eCognitive Testing Scores - SWM Strategy	-0.28 scores on a scale Standard Deviation 1.149	-0.92 scores on a scale Standard Deviation 1.459

SECONDARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Canakinumab n=9 Participants 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.	Placebo n=12 Participants Matching placebo subcutaneous injections
Change From Baseline in eCognitive Testing Scores - MTS Proportional Slowing 8-2 Patterns	143.780 Change from baseline in milliseconds Standard Deviation 2871.0641	77.573 Change from baseline in milliseconds Standard Deviation 2824.3325

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Canakinumab n=9 Participants 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.	Placebo n=12 Participants Matching placebo subcutaneous injections
Change From Baseline in eCognitive Testing Scores - PAL First Attempt Memory Score	-0.17 PAL score change from baseline Standard Deviation 2.716	0.08 PAL score change from baseline Standard Deviation 3.059

SECONDARY outcome

Timeframe: Baseline and day 85

Population: 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.

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.

Outcome measures

Outcome measures
Measure	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.	Placebo n=1 Participants Matching placebo subcutaneous injections
Change From Baseline in Microglia Activation as Measured by Positron-Emission Tomography-Translocator Protein 18kDa - Microglia Activation	—	NA Percent change from baseline Standard Deviation NA Only one participant completed day 85 PET TSPO, Data not reported in order to protect and maintain participant privacy/confidentiality.

SECONDARY outcome

Timeframe: Baseline, day29, day 57, day 85, day 141, day 171

Population: 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.

Serum pharmacokinetic pre-dose concentrations of CanakinumabConcentrations below the LLOQ were reported as "zero".

Outcome measures

Outcome measures
Measure	Canakinumab n=16 Participants 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.	Placebo Matching placebo subcutaneous injections
Serum Pharmacokinetic Concentrations of Canakinumab Baseline	0.0 ng/mL Standard Deviation 0.00	—
Serum Pharmacokinetic Concentrations of Canakinumab Day 29	8921.3 ng/mL Standard Deviation 2721.47	—
Serum Pharmacokinetic Concentrations of Canakinumab Day 57	14230.8 ng/mL Standard Deviation 4712.07	—
Serum Pharmacokinetic Concentrations of Canakinumab Day 85	26575.0 ng/mL Standard Deviation 10216.93	—
Serum Pharmacokinetic Concentrations of Canakinumab Day 141	34000.0 ng/mL Standard Deviation 11288.67	—
Serum Pharmacokinetic Concentrations of Canakinumab Day 171	33170.0 ng/mL Standard Deviation 6825.45	—

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Canakinumab n=15 Participants 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.	Placebo n=18 Participants Matching placebo subcutaneous injections
Total Target (IL-1 Beta) Concentration in Serum and CSF Serum - Baseline	0.000 pg/mL Standard Deviation 0.0000	0.000 pg/mL Standard Deviation 0.0000
Total Target (IL-1 Beta) Concentration in Serum and CSF Serum - Day 29	12.632 pg/mL Standard Deviation 4.4949	0.000 pg/mL Standard Deviation 0.0000
Total Target (IL-1 Beta) Concentration in Serum and CSF Serum - Day 57	20.818 pg/mL Standard Deviation 10.2918	0.000 pg/mL Standard Deviation 0.0000
Total Target (IL-1 Beta) Concentration in Serum and CSF Serum - Day 85	23.291 pg/mL Standard Deviation 5.2984	0.000 pg/mL Standard Deviation 0.0000
Total Target (IL-1 Beta) Concentration in Serum and CSF Serum - Day 141	44.473 pg/mL Standard Deviation 58.3963	0.000 pg/mL Standard Deviation 0.0000
Total Target (IL-1 Beta) Concentration in Serum and CSF Serum - Day 171	28.460 pg/mL Standard Deviation 18.4483	0.000 pg/mL Standard Deviation 0.0000
Total Target (IL-1 Beta) Concentration in Serum and CSF CSF - Baseline	0.000 pg/mL Standard Deviation 0.0000	0.000 pg/mL Standard Deviation 0.0000
Total Target (IL-1 Beta) Concentration in Serum and CSF CSF - Day 85	0.000 pg/mL Standard Deviation 0.0000	0.023 pg/mL Standard Deviation 0.0883

SECONDARY outcome

Timeframe: Baseline, day 85, day 171

Population: Participants in the safety analysis (SA) set who received Canakinumab. The SA set included all participants who received any study drug.

Number of participants with anti-agent antibodies in serum. Immunogenicity (IG) was assessed in serum of all participants treated with biotherapeutic drug.

Outcome measures

Outcome measures
Measure	Canakinumab n=16 Participants 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.	Placebo Matching placebo subcutaneous injections
Number of Participants With Anti-agent Antibodies in Serum Baseline · POSITIVE	0 Participants	—
Number of Participants With Anti-agent Antibodies in Serum Baseline · NEGATIVE	16 Participants	—
Number of Participants With Anti-agent Antibodies in Serum Day 85 · POSITIVE	0 Participants	—
Number of Participants With Anti-agent Antibodies in Serum Day 85 · NEGATIVE	12 Participants	—
Number of Participants With Anti-agent Antibodies in Serum Day 171 · POSITIVE	0 Participants	—
Number of Participants With Anti-agent Antibodies in Serum Day 171 · NEGATIVE	10 Participants	—

SECONDARY outcome

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

Population: The safety analysis set included all participants who received any study drug.

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

Outcome measures

Outcome measures
Measure	Canakinumab n=16 Participants 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.	Placebo n=18 Participants Matching placebo subcutaneous injections
Number of Participants Who Experience Adverse Events and Serious Adverse Events Participants with AEs leading to treatment discontinuation	3 Participants	1 Participants
Number of Participants Who Experience Adverse Events and Serious Adverse Events Participants with study drug related AEs leading to treatment discontinuation	1 Participants	0 Participants
Number of Participants Who Experience Adverse Events and Serious Adverse Events Participants with at least one AE	14 Participants	16 Participants
Number of Participants Who Experience Adverse Events and Serious Adverse Events Participants with grade 1 AEs	14 Participants	16 Participants
Number of Participants Who Experience Adverse Events and Serious Adverse Events Participants with grade 2 AEs	6 Participants	6 Participants
Number of Participants Who Experience Adverse Events and Serious Adverse Events Participants with grade 3 AEs	1 Participants	0 Participants
Number of Participants Who Experience Adverse Events and Serious Adverse Events Participants with study drug related AEs	4 Participants	5 Participants
Number of Participants Who Experience Adverse Events and Serious Adverse Events Participants with serious AEs	2 Participants	1 Participants

Adverse Events

Canakinumab

Serious events: 2 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Total

Serious events: 3 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Canakinumab n=16 participants at risk 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.	Placebo n=18 participants at risk Matching placebo subcutaneous injections	Total n=34 participants at risk Total
Infections and infestations COVID-19	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Streptococcal infection	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Nervous system disorders Metabolic encephalopathy	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: +1 862 778 8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Canakinumab n=16 participants at risk 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.	Placebo n=18 participants at risk Matching placebo subcutaneous injections	Total n=34 participants at risk Total
Blood and lymphatic system disorders Lymphopenia	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Ear and labyrinth disorders Vertigo positional	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Eye disorders Cataract	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Gastrointestinal disorders Abdominal hernia	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Gastrointestinal disorders Abdominal pain	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	11.1% 2/18 • From first dose up to approximately 140 days post last dose (day 281)	5.9% 2/34 • From first dose up to approximately 140 days post last dose (day 281)
Gastrointestinal disorders Abdominal tenderness	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Gastrointestinal disorders Diarrhoea	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Gastrointestinal disorders Diverticulum	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Gastrointestinal disorders Dyspepsia	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Gastrointestinal disorders Haemorrhoids	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Gastrointestinal disorders Inguinal hernia	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Gastrointestinal disorders Pancreatitis	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Immune system disorders Sensitisation	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Asymptomatic bacteriuria	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Conjunctivitis	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Lower respiratory tract infection	12.5% 2/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	5.9% 2/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Otitis externa	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Pneumonia	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Respiratory tract infection	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Rhinitis	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Tonsillitis	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Upper respiratory tract infection	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	5.9% 2/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Urinary tract infection	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	11.1% 2/18 • From first dose up to approximately 140 days post last dose (day 281)	8.8% 3/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Vaginal infection	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Viral infection	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Infections and infestations Viral upper respiratory tract infection	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Injury, poisoning and procedural complications Contusion	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Injury, poisoning and procedural complications Fall	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Injury, poisoning and procedural complications Immunisation reaction	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Injury, poisoning and procedural complications Post lumbar puncture syndrome	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Injury, poisoning and procedural complications Scratch	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Injury, poisoning and procedural complications Thermal burn	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Investigations Alanine aminotransferase increased	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Investigations Blood bilirubin increased	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Investigations Blood creatinine increased	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	11.1% 2/18 • From first dose up to approximately 140 days post last dose (day 281)	8.8% 3/34 • From first dose up to approximately 140 days post last dose (day 281)
Investigations Gamma-glutamyltransferase increased	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Investigations Lipase increased	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	11.1% 2/18 • From first dose up to approximately 140 days post last dose (day 281)	8.8% 3/34 • From first dose up to approximately 140 days post last dose (day 281)
Investigations Weight decreased	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Investigations White blood cells urine positive	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Musculoskeletal and connective tissue disorders Back pain	12.5% 2/16 • From first dose up to approximately 140 days post last dose (day 281)	11.1% 2/18 • From first dose up to approximately 140 days post last dose (day 281)	11.8% 4/34 • From first dose up to approximately 140 days post last dose (day 281)
Musculoskeletal and connective tissue disorders Muscle spasms	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Nervous system disorders Cognitive disorder	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Nervous system disorders Dizziness	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	11.1% 2/18 • From first dose up to approximately 140 days post last dose (day 281)	5.9% 2/34 • From first dose up to approximately 140 days post last dose (day 281)
Nervous system disorders Headache	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Nervous system disorders Intention tremor	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Nervous system disorders Ischaemic cerebral infarction	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Nervous system disorders Syncope	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Psychiatric disorders Agitation	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Psychiatric disorders Anxiety	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Psychiatric disorders Confusional state	12.5% 2/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	5.9% 2/34 • From first dose up to approximately 140 days post last dose (day 281)
Psychiatric disorders Irritability	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Psychiatric disorders Persecutory delusion	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Psychiatric disorders Procedural anxiety	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Renal and urinary disorders Acute kidney injury	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Renal and urinary disorders Proteinuria	12.5% 2/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	8.8% 3/34 • From first dose up to approximately 140 days post last dose (day 281)
Respiratory, thoracic and mediastinal disorders Cough	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Skin and subcutaneous tissue disorders Acne	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Skin and subcutaneous tissue disorders Eczema	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Skin and subcutaneous tissue disorders Rash	6.2% 1/16 • From first dose up to approximately 140 days post last dose (day 281)	0.00% 0/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Vascular disorders Flushing	0.00% 0/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	2.9% 1/34 • From first dose up to approximately 140 days post last dose (day 281)
Vascular disorders Hypertension	25.0% 4/16 • From first dose up to approximately 140 days post last dose (day 281)	5.6% 1/18 • From first dose up to approximately 140 days post last dose (day 281)	14.7% 5/34 • From first dose up to approximately 140 days post last dose (day 281)