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A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (GS2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03131453
Recruitment Status : Terminated (The study was terminated due to safety issues.)
First Posted : April 27, 2017
Results First Posted : August 5, 2021
Last Update Posted : August 5, 2021
Sponsor:
Collaborators:
Amgen
Banner Alzheimer's Institute
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimers Disease
Interventions Drug: CNP520 50mg
Drug: CNP520 15mg
Other: Matching placebo
Enrollment 1145
Recruitment Details  
Pre-assignment Details 8970 participants were screened
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description 50 mg capsule taken orally once daily 15 mg capsule taken orally once daily Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Period Title: Overall Study
Started 456 233 456
Patient Misrandomized 1 0 0
Completed 0 0 0
Not Completed 456 233 456
Reason Not Completed
Study terminated by Sponsor             424             222             438
Withdrawal by Subject             18             7             13
Adverse Event             10             3             3
Lost to Follow-up             1             0             1
Physician Decision             1             0             1
Non-compliance with study treatment             1             0             0
Technical problems             1             0             0
Protocol deviation             0             1             0
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo Total
Hide Arm/Group Description 50 mg capsule taken orally once daily 15 mg capsule taken orally once daily Matching placebo to 15 and 50 mg CNP520 taken orally once daily Total of all reporting groups
Overall Number of Baseline Participants 455 233 456 1144
Hide Baseline Analysis Population Description
One patient was misrandomized and not included in the CNP520 50mg arm
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 455 participants 233 participants 456 participants 1144 participants
<=64 76 45 80 201
65-69 181 82 162 425
>70 198 106 214 518
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 455 participants 233 participants 456 participants 1144 participants
Female
284
  62.4%
148
  63.5%
288
  63.2%
720
  62.9%
Male
171
  37.6%
85
  36.5%
168
  36.8%
424
  37.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 455 participants 233 participants 456 participants 1144 participants
Caucasian 416 213 422 1051
Black 7 1 5 13
Asian 18 12 22 52
Native American 3 2 1 6
Pacific Islander 2 1 0 3
Other 4 2 0 6
Unknown 5 2 6 13
Baseline cognitive scale assessment   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 455 participants 233 participants 456 participants 1144 participants
APCC score 74.6  (6.68) 75.8  (6.81) 74.9  (7.16) 75.0  (6.91)
RBANS Total 100.5  (11.96) 102.0  (12.09) 100.7  (12.42) 100.9  (12.18)
CDR-SOB 0.19  (0.389) 0.16  (0.358) 0.14  (0.358) 0.16  (0.371)
[1]
Measure Description: APCC(API Preclinical Composite Cognitive Battery) is a composite score derived from RBANS(Repeatable Battery for Assessment of Neurological Status), MMSE(Mini-Mental State Examination) and the Raven's Progressive Matrices; scores: 0-100/higher scores=better cognitive performance. RBANS is a tool to detect/characterize neurocognitive dementia changes in 5 neurocognitive domains; scores: 40-160/higher scores=better cognitive functioning. Clinical Dementia Rating Sum of Boxes(CDR-SOB) measures cognition+functioning in 6 domains; scores: 0-18/higher scores indicate greater disease severity
1.Primary Outcome
Title Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))
Hide Description Event was defined as the first confirmed diagnosis of MCI due to Alzheimer's disease (AD) or dementia due to AD (whichever occurred first) after adjudication by the progression adjudication committee (PAC) as triggered either by an investigator diagnosis or an increase in the Clinical Dementia Rating (CDR) global score. An event had to be confirmed by the PAC at two consecutive visits. In case no confirmed event was observed for a participant, the observation was censored, and the censoring date was defined as the last date where the diagnostic classification was assessed. The Study was terminated and only confirmed events collected up to the data cut-off point were counted. Due to the early termination of the study only a small number of events were observed and time-to-event could not be analyzed. Kaplan-Meyer (KM) estimates were provided to estimate probability that a subject would have an event prior to the specified visit.
Time Frame Baseline to last cognitive assessment performed (up to day 648)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set; n=number of participants at risk to experience an event at the time-point
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 455 233 456
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: probability of an event
Week 26 n=232,123,250 Number Analyzed 232 participants 123 participants 250 participants
0.99
(0.96 to 1.00)
1.00
(1.00 to 1.00)
1.00
(0.97 to 1.00)
Week 52 n=52,24,57 Number Analyzed 52 participants 24 participants 57 participants
0.97
(0.94 to 0.99)
0.99
(0.92 to 1.00)
0.99
(0.96 to 1.00)
Week 78 n=6,2,2 Number Analyzed 6 participants 2 participants 2 participants
0.97
(0.94 to 0.99)
0.99
(0.92 to 1.00)
0.97
(0.88 to 0.99)
2.Primary Outcome
Title Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
Hide Description APCC is a composite score derived from the specific scores from the Repeatable Battery for the Assessment of Neurological Status (RBANS), Mini-Mental State Examination (MMSE) and the Raven's Progressive Matrices. The APCC score is a weighted score with ranges from from 0 to 100 where higher scores correspond to better cognitive performance.
Time Frame Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 269 144 275
Mean (Standard Deviation)
Unit of Measure: Total scores
Week 26 n=160,79,162 Number Analyzed 160 participants 79 participants 162 participants
-3.1  (5.20) -2.9  (5.00) -1.7  (4.44)
Last on-treatment n=269,144,275 Number Analyzed 269 participants 144 participants 275 participants
-2.2  (4.88) -0.8  (4.67) -1.3  (5.21)
Last off-treatment n=255,124,260 Number Analyzed 255 participants 124 participants 260 participants
-0.8  (4.56) -0.8  (4.38) -0.8  (4.64)
3.Secondary Outcome
Title Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score
Hide Description The CDR was obtained through semi-structured interviews of participants and informants, and cognitive functioning was rated on a 5-point scale of functioning in six domains: memory, orientation, judgement and problem solving, community affairs, home and hobbies, and personal care. The CDR global score ranged from zero to three, while the CDR-SOB was the sum of the ratings from the six domains, ranging from 0 to 18 with a minimum increment of 0.5. Higher scores indicated greater disease severity
Time Frame Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 265 144 267
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Week 26 n=160,78,160 Number Analyzed 160 participants 78 participants 160 participants
0.17  (0.606) 0.20  (0.451) 0.08  (0.385)
Last on-treatment n=265,144,267 Number Analyzed 265 participants 144 participants 267 participants
0.15  (0.557) 0.08  (0.449) 0.10  (0.468)
Last off-treatment n=254,117,256 Number Analyzed 254 participants 117 participants 256 participants
0.09  (0.525) 0.07  (0.401) 0.10  (0.565)
4.Secondary Outcome
Title Change in the Total and Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Hide Description Repeatable Battery for the Assessment of Neurological Status (RBANS) is a clinical tool designed to detect and characterize the earliest neurocognitive changes associated with dementia. The RBANS generates age-adjusted index scores for five neurocognitive domains: Immediate Memory, Visuospatial/Constructional, Language, Attention and Delayed Memory, which are used to calculate a Total Scale Index score. Index scores and total score range from 40 to 160 and a higher score indicates better cognitive functioning.
Time Frame Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 356 183 353
Mean (Standard Deviation)
Unit of Measure: scores
Total Week 26 n=162,81,162 Number Analyzed 162 participants 81 participants 162 participants
-5.8  (8.54) -6.3  (8.58) -3.4  (8.35)
Total Last on-treatment n=356,183,353 Number Analyzed 356 participants 183 participants 353 participants
-3.4  (8.66) -3.5  (8.87) -0.5  (8.88)
Total Last off-treatment n=259,125,265 Number Analyzed 259 participants 125 participants 265 participants
-1.3  (8.12) -2.4  (9.55) -1.9  (8.56)
Immediate memory - Week 26 n=162,81,162 Number Analyzed 162 participants 81 participants 162 participants
-9.8  (11.85) -9.7  (12.10) -5.2  (11.26)
Immediate memory - Last on-treatment n=347,183,353 Number Analyzed 347 participants 183 participants 353 participants
-5.9  (13.01) -4.0  (13.54) -1.1  (13.04)
Immediate memory - Last off-treatment n=259,125,266 Number Analyzed 259 participants 125 participants 266 participants
-3.1  (12.50) -4.8  (13.52) -3.0  (13.00)
Visuospatial Week 26 n=162,81,162 Number Analyzed 162 participants 81 participants 162 participants
-5.6  (15.11) -5.4  (15.51) -2.6  (15.26)
Visuospatial Last on-treatment n=347,183,353 Number Analyzed 347 participants 183 participants 353 participants
-3.7  (14.90) -3.8  (15.14) -1.2  (13.95)
Visuospatial Last off-treatment n=259,125,266 Number Analyzed 259 participants 125 participants 266 participants
-1.5  (14.87) -0.7  (14.37) -1.2  (14.56)
Language Week 26 n=162,81,162 Number Analyzed 162 participants 81 participants 162 participants
-0.8  (11.48) -1.8  (11.05) -3.1  (11.07)
Language Last on-treatment n=347,183,353 Number Analyzed 347 participants 183 participants 353 participants
-0.3  (11.95) -1.7  (11.69) -1.3  (12.58)
Language Last off-treatment n=259,125,265 Number Analyzed 259 participants 125 participants 265 participants
-1.0  (10.93) -2.0  (12.68) -3.4  (11.47)
Attention Week 26 n=162,81,162 Number Analyzed 162 participants 81 participants 162 participants
0.1  (11.19) -0.1  (10.37) 0.1  (10.56)
Attention Last on-treatment n=347,183,353 Number Analyzed 347 participants 183 participants 353 participants
0.0  (11.30) 0.0  (10.68) 0.7  (10.99)
Attention Last off-treatment n=259,125,265 Number Analyzed 259 participants 125 participants 265 participants
1.6  (11.59) 1.7  (10.65) 1.1  (9.81)
Delayed memory - Week 26 n=162,81,162 Number Analyzed 162 participants 81 participants 162 participants
-5.5  (11.54) -5.0  (11.68) -2.1  (11.69)
Delayed memory - Last on-treatment n=346,183,353 Number Analyzed 346 participants 183 participants 353 participants
-3.0  (11.58) -2.8  (10.56) 0.8  (11.43)
Delayed memory - Last off-treatment n=259,125,265 Number Analyzed 259 participants 125 participants 265 participants
-1.0  (10.91) -2.5  (10.34) -0.5  (10.57)
5.Secondary Outcome
Title Change in the Everyday Cognition Scale (ECog-Subject) Total Scores
Hide Description Everyday Cognition Scale (ECog) measures cognitively-relevant everyday abilities comprised of 39 items covering 6 cognitively-relevant domains: Everyday Memory, Everyday Language, Everyday Visuospatial Abilities, Everyday Planning, Everyday Organization, and Everyday Divided Attention. The questionnaire is a self-reported measure completed by both participant and study partner (informant). The total score for the 39 items ranges from 39 to 195, with greater scores indicating worse daily function.
Time Frame Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 266 143 268
Mean (Standard Deviation)
Unit of Measure: Total scores
Week 26 n=155,78,157 Number Analyzed 155 participants 78 participants 157 participants
0.9  (7.90) 0.2  (5.52) 0.5  (6.76)
Last on-treatment n=266,143,268 Number Analyzed 266 participants 143 participants 268 participants
1.6  (8.03) 0.4  (5.62) 0.7  (8.25)
Last off-treatment n=249,122,255 Number Analyzed 249 participants 122 participants 255 participants
-0.1  (6.49) 0.0  (7.02) 0.1  (7.47)
6.Secondary Outcome
Title Change in the Everyday Cognition Scale (ECog-Informant) Total Scores
Hide Description Everyday Cognition Scale (ECog) measures cognitively-relevant everyday abilities comprised of 39 items covering 6 cognitively-relevant domains: Everyday Memory, Everyday Language, Everyday Visuospatial Abilities, Everyday Planning, Everyday Organization, and Everyday Divided Attention. The questionnaire is a self-reported measure completed by both participant and study partner (informant). The total score for the 39 items ranges from 39 to 195, with greater scores indicating worse daily function.
Time Frame Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 252 138 255
Mean (Standard Deviation)
Unit of Measure: Total scores
Week 26 n=153,76,153 Number Analyzed 153 participants 76 participants 153 participants
-0.3  (7.55) 1.7  (7.77) -1.2  (6.10)
Last on-treatment n=252,138,255 Number Analyzed 252 participants 138 participants 255 participants
0.5  (7.58) 0.7  (8.49) 0.2  (7.00)
Last off-treatment n=223,113,239 Number Analyzed 223 participants 113 participants 239 participants
0.5  (6.97) 0.0  (6.74) 1.2  (9.36)
7.Secondary Outcome
Title Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)
Hide Description Safety MRI included sequences necessary for ascertainment of possible ARIA-E (Amyloid Related Imaging Abnormality-Edema), ARIA-H (Amyloid Related Imaging Abnormality- Hemorrhage, including superficial siderosis and microhemorrhages), assessment of recent infarcts and white matter integrity examination (White matter disease worsening) and a general assessment of brain abnormalities.
Time Frame Baseline up to study termination approximately 617 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 455 233 456
Measure Type: Count of Participants
Unit of Measure: Participants
Presence of ARIA-H
0
   0.0%
0
   0.0%
0
   0.0%
Questionable presence of ARIA-E
1
   0.2%
0
   0.0%
2
   0.4%
White matter disease worsening: 1-3 increase
4
   0.9%
2
   0.9%
3
   0.7%
White matter disease worsening: 4- - >8 increase
0
   0.0%
0
   0.0%
0
   0.0%
White matter disease worsening >8
0
   0.0%
0
   0.0%
0
   0.0%
Any other MRI abnormalities
1
   0.2%
0
   0.0%
1
   0.2%
8.Secondary Outcome
Title Annualized Percent Change on Volume of Brain Regions
Hide Description Annualized % change from baseline in volume of specific brain regions of interest (ROIs): whole brain (WB), hippocampus (Hip), and lateral ventricles (LV). Annualized percentage change was calculated as (percentage per participant / time interval (in days)) x 365.25. Time interval (in days) was derived as date of current MRI assessment on study drug - date of baseline MRI assessment + 1.
Time Frame Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 179 85 182
Mean (Standard Deviation)
Unit of Measure: Percentage of volume change
WB Week 26 n=169,83,169 Number Analyzed 169 participants 83 participants 169 participants
-1.1016  (1.03196) -0.9348  (0.85477) -0.5552  (1.21385)
WB Last on-treatment n=179,85,182 Number Analyzed 179 participants 85 participants 182 participants
-1.0427  (0.93751) -0.9205  (0.75633) -0.5378  (1.09542)
WB Last off-treatment n=72,44,81 Number Analyzed 72 participants 44 participants 81 participants
-0.6984  (0.73644) -0.9188  (0.94516) -0.5811  (0.75412)
Hip Week 26 n=169,83,169 Number Analyzed 169 participants 83 participants 169 participants
-2.0993  (2.77159) -1.9100  (2.31406) -1.2113  (2.71764)
Hip Last on-treatment n=179,85,182 Number Analyzed 179 participants 85 participants 182 participants
-2.0052  (2.65898) -1.7909  (2.06883) -1.1628  (2.56183)
Hip Last off-treatment n=72,44,81 Number Analyzed 72 participants 44 participants 81 participants
-1.3755  (1.90613) -1.2522  (2.23213) -1.1929  (1.81333)
LV Week 26 n=169,83,169 Number Analyzed 169 participants 83 participants 169 participants
5.4388  (5.91870) 5.3457  (4.67788) 3.5415  (4.75268)
LV Last on-treatment n=179,85,182 Number Analyzed 179 participants 85 participants 182 participants
5.0974  (5.31542) 5.0822  (3.88165) 3.4582  (4.35888)
LV Last off-treatment n=72,44,81 Number Analyzed 72 participants 44 participants 81 participants
4.0014  (4.29087) 3.9355  (5.17657) 3.3851  (3.38576)
9.Secondary Outcome
Title Change in CSF Levels of Amyloid Beta 40 (Aβ40)
Hide Description Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): Amyloid Beta 40 (Aβ40)
Time Frame Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 16 5 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
AB40 Last on-treatment n=1,0,1 Number Analyzed 1 participants 0 participants 1 participants
-7.320 -0.760
AB40 Last off-treatment n=16,5,13 Number Analyzed 16 participants 5 participants 13 participants
-1.492  (1.9263) 0.804  (1.9220) -1.172  (1.7408)
10.Secondary Outcome
Title Change in CSF Levels of Amyloid Beta 42 (Aβ42)
Hide Description Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): Amyloid Beta 42 (Aβ42).
Time Frame Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 16 5 13
Mean (Standard Deviation)
Unit of Measure: pg/mL
AB42 Last on-treatment n=1,0,1 Number Analyzed 1 participants 0 participants 1 participants
-366.200 -61.300
AB42 Last off-treatment n=16,5,13 Number Analyzed 16 participants 5 participants 13 participants
20.431  (74.5595) -68.660  (62.8505) 21.246  (104.3395)
11.Secondary Outcome
Title Change in Neurofibrillary Tangle Burden as Measured by Standardized Uptake Ratio (SUVR) of PET Scans With Tau Radiotracer (Where Available)
Hide Description To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers
Time Frame Baseline to Months 24 and 60
Hide Outcome Measure Data
Hide Analysis Population Description
No available data since no post-baseline (month 24 and 60) PET scan could be obtained due to the early termination of the trial.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
12.Secondary Outcome
Title Change in Amyloid Deposition as Measured by Standardized Uptake Ratio (SUVR) of Positron Emission Tomography (PET) Scan With Amyloid Radiotracer
Hide Description To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers
Time Frame Baseline to Months 24 and 60
Hide Outcome Measure Data
Hide Analysis Population Description
No available data since no post-baseline (month 24 and 60) PET scan could be obtained due to the early termination of the trial.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
13.Secondary Outcome
Title Change in CSF Levels of Total Tau and Phosphorylated Tau
Hide Description Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): total tau protein and phosphorylated tau protein levels
Time Frame Baseline to Last on-treatment (Day 547) Baseline to Last off-treatment (Day 648)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 16 5 13
Mean (Standard Deviation)
Unit of Measure: pg/mL
Total tau - Last on-treatment n=1,0,1 Number Analyzed 1 participants 0 participants 1 participants
40.000 -12.600
Total tau - Last off-treatment n=16,5,13 Number Analyzed 16 participants 5 participants 13 participants
-22.119  (28.6218) -3.320  (21.1548) -3.238  (23.4442)
Phosphorylated tau - Last on-treatment n=1,0,1 Number Analyzed 1 participants 0 participants 1 participants
-2.360 -0.550
Phosphorylated tau - Last off-treatment n=16,5,13 Number Analyzed 16 participants 5 participants 13 participants
-1.849  (2.3397) -0.852  (2.7005) 0.065  (1.3032)
14.Secondary Outcome
Title Change in Serum Neurofilaments
Hide Description Alzheimer's Disease-related biomarkers analyzed in blood serum: light chain neurofilaments (NfL)
Time Frame Baseline to Week 26, baseline to Last on-treatment (Day 547) Baseline to Last off-treatment (Day 648)
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Hide Analysis Population Description
Safety analysis set - only participants with a value at both Baseline and that visit are included. Last on-treatment is the last assessment before or at last day on study drug + 31 days. Last off-treatment is the last assessment after last day on study drug + 31 days.
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 33 17 40
Mean (Standard Deviation)
Unit of Measure: pg/mL
Week 26 n=33,17,38 Number Analyzed 33 participants 17 participants 38 participants
0.622  (4.5576) 0.901  (4.6732) -5.731  (40.9042)
Last on-treatment n=33,15,40 Number Analyzed 33 participants 15 participants 40 participants
0.932  (4.2494) 0.041  (3.4144) -5.771  (39.8254)
Last off-treatment n=5,2,1 Number Analyzed 5 participants 2 participants 1 participants
-2.764  (3.0981) 7.350  (9.5884) 3.880
15.Secondary Outcome
Title Number of Suicidal Ideation or Behavior Events
Hide Description Prospective suicidality assessment was performed with the use of Columbia-Suicide Severity Rating Scale (C-SSRS), a questionnaire using a detailed branched logic algorithm evaluating participant's suicidality ideation and behavior. Answer "yes" on item 4 or 5 of the Suicidal Ideation section or "yes" on any item of the Suicidal Behavior section was considered positive.
Time Frame Baseline up to study termination approximately 617 days
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Hide Analysis Population Description
Safety analysis set which includes only participants with events
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description:
50 mg capsule taken orally once daily
15 mg capsule taken orally once daily
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Overall Number of Participants Analyzed 455 233 456
Measure Type: Number
Unit of Measure: events
Any suicidal ideation n=13,3,9 Number Analyzed 13 participants 3 participants 9 participants
25 6 12
Any suicidal behavior n=1,0,1 Number Analyzed 1 participants 0 participants 1 participants
1 1
Time Frame Adverse events were reported from first dose of study treatment until end of study treatment plus 31 days of washout period for a maximum duration of 617 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title CNP520 50 mg CNP520 15 mg Placebo
Hide Arm/Group Description 50 mg capsule taken orally once daily 15 mg capsule taken orally once daily Matching placebo to 15 and 50 mg CNP520 taken orally once daily
All-Cause Mortality
CNP520 50 mg CNP520 15 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/455 (0.00%)   0/233 (0.00%)   0/456 (0.00%) 
Hide Serious Adverse Events
CNP520 50 mg CNP520 15 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   15/455 (3.30%)   9/233 (3.86%)   15/456 (3.29%) 
Cardiac disorders       
Aortic valve incompetence  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
Coronary artery disease  1  2/455 (0.44%)  1/233 (0.43%)  0/456 (0.00%) 
Mitral valve incompetence  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
Supraventricular tachycardia  1  0/455 (0.00%)  1/233 (0.43%)  1/456 (0.22%) 
Gastrointestinal disorders       
Colitis ulcerative  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Nausea  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
Pancreatitis  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
General disorders       
Non-cardiac chest pain  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Hepatobiliary disorders       
Drug-induced liver injury  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Hepatic cirrhosis  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
Infections and infestations       
Pneumonia  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Pneumonia influenzal  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Injury, poisoning and procedural complications       
Femur fracture  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Fibula fracture  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Radius fracture  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Subdural haematoma  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Traumatic lung injury  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Investigations       
Haemoglobin decreased  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Hepatic enzyme increased  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Serum ferritin decreased  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Musculoskeletal and connective tissue disorders       
Musculoskeletal chest pain  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
Osteoarthritis  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
Bladder transitional cell carcinoma  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Breast cancer  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Chordoma  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Endometrial cancer  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Intraductal proliferative breast lesion  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Malignant melanoma  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Squamous cell carcinoma  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Squamous cell carcinoma of skin  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Nervous system disorders       
Cerebellar infarction  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
Cerebrovascular accident  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Dizziness  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
Generalised tonic-clonic seizure  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Headache  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Ischaemic stroke  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Parkinson's disease  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Seizure  1  1/455 (0.22%)  1/233 (0.43%)  0/456 (0.00%) 
Transient ischaemic attack  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
Psychiatric disorders       
Major depression  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Mania  1  1/455 (0.22%)  0/233 (0.00%)  0/456 (0.00%) 
Suicidal ideation  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
Renal and urinary disorders       
Acute kidney injury  1  0/455 (0.00%)  0/233 (0.00%)  1/456 (0.22%) 
Vascular disorders       
Aortic aneurysm  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
Hypertension  1  0/455 (0.00%)  1/233 (0.43%)  0/456 (0.00%) 
1
Term from vocabulary, MedDRA (23.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2.5%
CNP520 50 mg CNP520 15 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   137/455 (30.11%)   62/233 (26.61%)   89/456 (19.52%) 
Infections and infestations       
Bronchitis  1  6/455 (1.32%)  7/233 (3.00%)  4/456 (0.88%) 
Nasopharyngitis  1  22/455 (4.84%)  9/233 (3.86%)  11/456 (2.41%) 
Upper respiratory tract infection  1  18/455 (3.96%)  5/233 (2.15%)  16/456 (3.51%) 
Urinary tract infection  1  8/455 (1.76%)  8/233 (3.43%)  7/456 (1.54%) 
Injury, poisoning and procedural complications       
Fall  1  11/455 (2.42%)  7/233 (3.00%)  5/456 (1.10%) 
Investigations       
Weight decreased  1  19/455 (4.18%)  3/233 (1.29%)  7/456 (1.54%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  11/455 (2.42%)  6/233 (2.58%)  11/456 (2.41%) 
Back pain  1  14/455 (3.08%)  2/233 (0.86%)  4/456 (0.88%) 
Nervous system disorders       
Dizziness  1  14/455 (3.08%)  7/233 (3.00%)  8/456 (1.75%) 
Headache  1  12/455 (2.64%)  8/233 (3.43%)  15/456 (3.29%) 
Psychiatric disorders       
Abnormal dreams  1  18/455 (3.96%)  7/233 (3.00%)  3/456 (0.66%) 
Anxiety  1  21/455 (4.62%)  4/233 (1.72%)  8/456 (1.75%) 
Skin and subcutaneous tissue disorders       
Pruritus  1  32/455 (7.03%)  12/233 (5.15%)  16/456 (3.51%) 
1
Term from vocabulary, MedDRA (23.0)
Indicates events were collected by systematic assessment
The study was terminated due to safety issues.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: + 1 862 778 8300
EMail: Novartis.email@Novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT03131453    
Other Study ID Numbers: CCNP520A2202J
2016-002976-28 ( EudraCT Number )
First Submitted: April 5, 2017
First Posted: April 27, 2017
Results First Submitted: March 25, 2021
Results First Posted: August 5, 2021
Last Update Posted: August 5, 2021