GS1

TerminatedPhase 2 / PHASE3Results posted

A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease

A Randomized, Double-blind, Placebo-controlled, Two-cohort, Parallel Group Study to Evaluate the Efficacy of CAD106 and CNP520 in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease.

Lead sponsor

Novartis Pharmaceuticals

Assets

CAD106 / Umibecestat

Listed sites

129

Recruiting sites

Enrollment

480

actual

Study population

Alzheimer’s disease

Key I/E criteria

•MMSE ≥24•Study partner/caregiver required

Primary endpoints

•Event•Mini-Mental State Examination (MMSE)

Footprint

Where this trial recruits

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

Identifiers

Registered as

Nih1UF1AG046150-01

Eudract number2015-002715-15

Org study IDCAPI015A2201J

NCT IDNCT02565511

Timeline

Milestones

Study first posted2015-10-01estimated

Study start2015-11-30actual

Primary completion2020-04-30actual

Study completion2020-04-30actual

Last update posted2021-07-08actual

Results first posted2021-07-08actual

Assets

Drug assets

CAD106 Umibecestat

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age60 Years

Maximum age75 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

Key Inclusion Criteria:

•Consented to receive disclosure of their risk estimates to develop clinical symptoms of AD based on their APOE genotype.

•Male or female, age 60 to 75 years inclusive. Females were to be post-menopausal.

•Mini-Mental State Examination (MMSE) total score ≥ 24 and cognitively unimpaired as evaluated by memory tests

•Homozygous APOE4 genotype.

•Participant willing to have a study partner

Exclusion criteria

•Any disability that prevented the participant from completing all study requirements.

•Current medical or neurological condition that could have impacted cognition or performance on cognitive assessments.

•Advanced, severe progressive or unstable disease that may have interfered with the safety, tolerability and study assessments, or put the participant at special risk.

•History of malignancy of any organ system, treated or untreated, within 60 months prior to screening.

•History of hypersensitivity to any of the investigational drugs or their excipients / adjuvant or to drugs of similar chemical classes.

•Indication or on current treatment with ChEIs and/or another AD treatment (e.g. memantine).

•Contraindication or intolerance to MRI or PET investigations (with fluorinated radio ligands).

•Brain MRI results showing findings unrelated to AD that, in the opinion of the Investigator could have been a leading cause to future cognitive decline, pose a risk to the participant, or prevent a satisfactory MRI assessment for safety monitoring.

•Suicidal Ideation in the past six months or Suicidal Behavior in the past two years, prior to screening.

•A positive drug screen at Screening, if, in the Investigator's opinion, this was due to drug abuse.

•Significantly abnormal laboratory results at Screening, or infection not as a result of a temporary condition.

•Current clinically significant ECG findings. For Cohort - I only: Participants with previous organ transplantation or stem cell transplantation, or indication for treatment with anti-coagulants.

For Cohort - II only: Participants with depigmenting or hypopigmenting conditions (e.g. albinism vitiligo) or active / history of chronic urticarial in the past year.

Endpoints (38)

What's being measured

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

Coverage by outcome category

Global cognition

Amyloid biomarkers

Memory

Neuroimaging

Behavior / neuropsychiatric

Tau biomarkers

Neurodegeneration biomarkers

Global cognition

12 endpoints

Primary/protocol endpoint

Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))

Time frame:Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII

time to event, event

Primary/protocol endpoint

Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score

Time frame:CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatment

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Primary/registry result

Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))

Time frame:Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII

time to event, event

Posted result

Group	Value (number), proportion of participants	Reported bounds
Cohort I (CI) CAD106Week 26n=41 Participants	1.00	-1.00 - 1.00
Week 52n=40 Participants	1.00	-1.00 - 1.00
Week 78n=37 Participants	0.97	-0.83 - 1.00
Week 104n=22 Participants	0.97	-0.83 - 1.00
Cohort I (CI) CAD106 PlaceboWeek 26n=22 Participants	1.00	-1.00 - 1.00
Week 52n=22 Participants	1.00	-1.00 - 1.00
Week 78n=21 Participants	1.00	-1.00 - 1.00
Week 104n=15 Participants	1.00	-1.00 - 1.00
Cohort II (CII) CNP520Week 26n=193 Participants	0.98	-0.95 - 0.99
Week 52n=95 Participants	0.93	-0.88 - 0.96
Week 78n=18 Participants	0.88	-0.79 - 0.93
Week 104n=5 Participants	0.88	-0.79 - 0.93
Cohort II (CII) CNP520 PlaceboWeek 26n=126 Participants	0.98	-0.94 - 0.99
Week 52n=63 Participants	0.95	-0.90 - 0.98
Week 78n=9 Participants	0.85	-0.63 - 0.94
Week 104n=2 Participants	0.85	-0.63 - 0.94

Primary/registry result

Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score

Time frame:CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatment

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), Total scores	Standard deviation
Cohort I (CI) CAD106Week 26n=41 Participants	-1.1	4.10
Week 52n=41 Participants	0.9	4.24
Week 78n=27 Participants	0.2	4.15
Week 104n=17 Participants	-1.4	4.67
CI-Last post BL assessmentn=41 Participants	0.0	4.62
Cohort I (CI) CAD106 PlaceboWeek 26n=23 Participants	-2.0	3.90
Week 52n=22 Participants	1.4	3.36
Week 78n=18 Participants	-0.7	5.48
Week 104n=9 Participants	0.3	4.00
CI-Last post BL assessmentn=23 Participants	0.1	3.87
Cohort II (CII) CNP520Week 26n=154 Participants	-3.3	4.54
Week 52n=64 Participants	0.3	4.27
Week 78n=7 Participants	-4.1	4.14
Week 104n=3 Participants	-6.7	3.95
CII - Last on treatmentn=179 Participants	-1.7	4.81
CII-Last off treatmentn=166 Participants	-0.1	4.72
Cohort II (CII) CNP520 PlaceboWeek 26n=105 Participants	-1.0	4.65
Week 52n=36 Participants	2.2	6.11
Week 78n=8 Participants	2.4	4.23
CII - Last on treatmentn=125 Participants	0.1	4.58
CII-Last off treatmentn=90 Participants	0.2	4.56

Secondary/protocol endpoint

Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score

Time frame:CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatment

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Change in the Total Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Time frame:CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatment

change from baseline, improvement

Secondary/protocol endpoint

Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Time frame:CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment

change from baseline, improvement

Secondary/protocol endpoint

Cohort I : Change in Cognition as Measured by APCC and CDR-SOB Scores and Antibody Response

Time frame:Month 6 to Month 60

change from baseline, improvement

Secondary/registry result

Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score

Time frame:CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatment

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (mean), Scores on a scale	Standard deviation
Cohort I (CI) CAD106Week 26n=41 Participants	-0.04	0.234
Week 52n=41 Participants	-0.01	0.237
Week 78n=27 Participants	-0.04	0.237
Week 104n=17 Participants	0.15	0.460
CI Last post baseline assessmentn=41 Participants	0.04	0.343
Cohort I (CI) CAD106 PlaceboWeek 26n=23 Participants	0.00	0.000
Week 52n=23 Participants	0.02	0.104
Week 78n=18 Participants	0.03	0.118
Week 104n=9 Participants	0.06	0.167
CI Last post baseline assessmentn=23 Participants	0.00	0.302
Cohort II (CII) CNP520Week 26n=153 Participants	0.04	0.361
Week 52n=64 Participants	-0.02	0.281
Week 78n=7 Participants	0.14	0.802
Week 104n=3 Participants	-0.17	0.764
CII Last on-treatmentn=174 Participants	0.06	0.505
CII Last off-treatmentn=156 Participants	0.05	0.464
Cohort II (CII) CNP520 PlaceboWeek 26n=105 Participants	0.00	0.336
Week 52n=36 Participants	-0.08	0.541
Week 78n=7 Participants	-0.14	0.244
CII Last on-treatmentn=122 Participants	0.03	0.410
CII Last off-treatmentn=90 Participants	-0.01	0.519

Secondary/registry result

Change in the Total Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Time frame:CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatment

change from baseline, improvement

Posted result

Group	Value (mean), scores	Standard deviation
Cohort I (CI) CAD106Total Week 26n=41 Participants	-5.1	7.25
Total Week 52n=41 Participants	-1.2	7.82
Total Week 78n=27 Participants	-2.1	7.69
Total Week 104n=17 Participants	-1.4	6.74
Total CI Last post baseline assessmentn=41 Participants	-1.0	9.27
Cohort I (CI) CAD106 PlaceboTotal Week 26n=23 Participants	-3.0	7.51
Total Week 52n=22 Participants	4.5	7.10
Total Week 78n=18 Participants	-4.0	7.82
Total Week 104n=9 Participants	-3.0	8.34
Total CI Last post baseline assessmentn=23 Participants	0.4	7.20
Cohort II (CII) CNP520Total Week 26n=154 Participants	-4.1	8.58
Total Week 52n=64 Participants	-0.1	7.91
Total Week 78n=7 Participants	-12.1	7.40
Total Week 104n=3 Participants	-7.7	15.57
Total CII Last on-treatmentn=209 Participants	-2.7	8.65
Total CII Last off-treatmentn=169 Participants	-1.5	9.20
Cohort II (CII) CNP520 PlaceboTotal Week 26n=105 Participants	-2.6	7.83
Total Week 52n=37 Participants	1.4	8.06
Total Week 78n=8 Participants	-4.8	5.99
Total CII Last on-treatmentn=141 Participants	-0.2	9.22
Total CII Last off-treatmentn=93 Participants	-0.6	8.83

Secondary/registry result

Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Time frame:CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment

change from baseline, improvement

Posted result

Group	Value (mean), scores	Standard deviation
Cohort I (CI) CAD106Immediate memory - Week 26n=41 Participants	-8.6	10.68
Immediate memory - Week 52n=41 Participants	1.3	10.81
CI Immediate memory - Last post baseline assessmentn=41 Participants	-1.1	13.11
Visuospatial Week 26n=41 Participants	-6.5	15.21
Visuospatial Week 52n=41 Participants	-6.5	14.59
CI Visuospatial Last post baseline assessmentn=41 Participants	-4.7	13.91
Language Week 26n=41 Participants	-1.4	12.91
Language Week 52n=41 Participants	2.6	10.29
CI Language Last post baseline assessmentn=41 Participants	1.9	13.00
Attention Week 26n=41 Participants	1.8	9.40
Attention Week 52n=41 Participants	0.9	10.80
CI Attention Last post baseline assessmentn=41 Participants	2.0	12.91
Delayed memory - Week 26n=41 Participants	-3.8	7.83
Delayed memory - Week 52n=41 Participants	-2.0	8.01
CI Delayed memory - Last post baseline assessmentn=41 Participants	-1.0	10.20
Cohort I (CI) CAD106 PlaceboImmediate memory - Week 26n=23 Participants	-3.8	11.16
Immediate memory - Week 52n=22 Participants	4.8	8.68
CI Immediate memory - Last post baseline assessmentn=23 Participants	1.1	14.52
Visuospatial Week 26n=23 Participants	0.7	12.39
Visuospatial Week 52n=22 Participants	3.0	15.09
CI Visuospatial Last post baseline assessmentn=23 Participants	1.9	12.72
Language Week 26n=23 Participants	-2.8	11.42
Language Week 52n=22 Participants	2.0	11.51
CI Language Last post baseline assessmentn=23 Participants	-4.5	12.86
Attention Week 26n=23 Participants	-0.6	14.19
Attention Week 52n=22 Participants	-0.5	13.09
CI Attention Last post baseline assessmentn=23 Participants	2.0	10.25
Delayed memory - Week 26n=23 Participants	-2.7	7.64
Delayed memory - Week 52n=22 Participants	3.2	6.23
CI Delayed memory - Last post baseline assessmentn=23 Participants	1.3	8.44
Cohort II (CII) CNP520Immediate memory - Week 26n=154 Participants	-7.4	13.11
Immediate memory - Week 52n=64 Participants	0.6	13.55
CII Immediate memory - Last on-treatmentn=209 Participants	-3.7	14.43
CII Immediate memory - Last off-treatmentn=169 Participants	-3.2	13.76
Visuospatial Week 26n=154 Participants	-3.5	14.98
Visuospatial Week 52n=64 Participants	-1.4	14.29
CII Visuospatial Last on-treatment n=n=209 Participants	-3.5	14.59
CII Visuospatial Last off-treatmentn=169 Participants	-1.2	15.13
Language Week 26n=154 Participants	-0.1	12.05
Language Week 52n=64 Participants	-0.3	12.88
CII Language Last on-treatmentn=209 Participants	-0.1	12.07
CII Language Last off-treatmentn=169 Participants	-1.0	13.19
Attention Week 26n=154 Participants	-0.7	10.42
Attention Week 52n=64 Participants	-0.2	10.02
CII Attention Last on-treatmentn=209 Participants	0.1	10.80
CII-Attention Last off-treatmentn=169 Participants	1.0	1.64
Delayed memory - Week 26n=154 Participants	-3.8	11.20
Delayed memory - Week 52n=64 Participants	2.3	9.09
CII Delayed memory - Last on-treatmentn=209 Participants	-2.5	10.61
CII Delayed memory - Last off-treatmentn=169 Participants	-1.1	10.75
Cohort II (CII) CNP520 PlaceboImmediate memory - Week 26n=105 Participants	-3.7	12.15
Immediate memory - Week 52n=37 Participants	5.1	11.73
CII Immediate memory - Last on-treatmentn=141 Participants	0.6	13.54
CII Immediate memory - Last off-treatmentn=93 Participants	-2.0	11.90
Visuospatial Week 26n=105 Participants	-2.4	13.00
Visuospatial Week 52n=37 Participants	-4.8	12.60
CII Visuospatial Last on-treatment n=n=141 Participants	-2.6	14.92
CII Visuospatial Last off-treatmentn=93 Participants	-0.8	15.18
Language Week 26n=105 Participants	-1.5	11.87
Language Week 52n=37 Participants	0.8	9.72
CII Language Last on-treatmentn=141 Participants	-0.1	11.93
CII Language Last off-treatmentn=93 Participants	-1.8	11.25
Attention Week 26n=105 Participants	-0.6	11.67
Attention Week 52n=37 Participants	2.7	10.77
CII Attention Last on-treatmentn=141 Participants	0.8	11.20
CII-Attention Last off-treatmentn=93 Participants	1.2	11.07
Delayed memory - Week 26n=105 Participants	-2.6	8.85
Delayed memory - Week 52n=37 Participants	0.6	11.73
CII Delayed memory - Last on-treatmentn=141 Participants	0.4	10.28
CII Delayed memory - Last off-treatmentn=93 Participants	1.1	11.28

Secondary/registry result

Cohort I : Change in Cognition as Measured by APCC and CDR-SOB Scores and Antibody Response

Time frame:Month 6 to Month 60

change from baseline, improvement

Memory

4 endpoints

Secondary/protocol endpoint

Change in the Everyday Cognition Scale (ECog-Subject) Total Scores

Time frame:CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment

change from baseline, improvement

Secondary/protocol endpoint

Change in the Everyday Cognition Scale (ECog-Informant) Total Scores

Time frame:CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment

change from baseline, improvement

Secondary/registry result

Change in the Everyday Cognition Scale (ECog-Subject) Total Scores

Time frame:CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment

change from baseline, improvement

Posted result

Group	Value (mean), Total scores	Standard deviation
Cohort I (CI) CAD106Week 26n=40 Participants	-1.0	2.94
Week 52n=40 Participants	0.6	5.23
CI Last post baseline assessmentn=40 Participants	0.6	5.02
Cohort I (CI) CAD106 PlaceboWeek 26n=22 Participants	2.3	4.80
Week 52n=21 Participants	0.4	2.99
CI Last post baseline assessmentn=22 Participants	1.6	4.07
Cohort II (CII) CNP520Week 26n=151 Participants	1.8	6.03
Week 52n=63 Participants	2.7	6.16
CII Last on-treatmentn=178 Participants	2.6	7.81
CII Last off-treatmentn=162 Participants	1.6	6.77
Cohort II (CII) CNP520 PlaceboWeek 26n=103 Participants	0.6	6.45
Week 52n=37 Participants	0.2	5.01
CII Last on-treatmentn=119 Participants	0.9	6.48
CII Last off-treatmentn=86 Participants	0.8	6.13

Secondary/registry result

Change in the Everyday Cognition Scale (ECog-Informant) Total Scores

Time frame:CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment

change from baseline, improvement

Posted result

Group	Value (mean), Total scores	Standard deviation
Cohort I (CI) CAD106Week 26n=37 Participants	-0.4	4.21
Week 52n=37 Participants	-0.2	3.15
CI Last post baseline assessmentn=37 Participants	-1.1	4.23
Cohort I (CI) CAD106 PlaceboWeek 26n=23 Participants	-1.0	4.87
Week 52n=22 Participants	-0.3	5.12
CI Last post baseline assessmentn=23 Participants	-1.0	4.88
Cohort II (CII) CNP520Week 26n=142 Participants	0.1	6.84
Week 52n=57 Participants	1.4	5.18
CII Last on-treatmentn=160 Participants	1.3	8.76
CII Last off-treatmentn=143 Participants	1.4	8.49
Cohort II (CII) CNP520 PlaceboWeek 26n=95 Participants	-0.7	8.69
Week 52n=29 Participants	-0.2	9.59
CII Last on-treatmentn=113 Participants	0.1	9.12
CII Last off-treatmentn=77 Participants	-0.5	10.10

Behavior / neuropsychiatric

2 endpoints

Secondary/protocol endpoint

Number of Suicidal Ideation or Behavior Events

Time frame:Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII

event count, event

Secondary/registry result

Number of Suicidal Ideation or Behavior Events

Time frame:Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII

event count, event

Posted result

Group	Value (number), events	Reported bounds
Cohort I (CI) CAD106Any suicidal ideationn=42 Participants	2	-
Any suicidal behaviorn=42 Participants	0	-
Cohort I (CI) CAD106 PlaceboAny suicidal ideationn=23 Participants	1	-
Any suicidal behaviorn=23 Participants	0	-
Cohort II (CII) CNP520Any suicidal ideationn=249 Participants	12	-
Any suicidal behaviorn=249 Participants	1	-
Cohort II (CII) CNP520 PlaceboAny suicidal ideationn=163 Participants	4	-
Any suicidal behaviorn=163 Participants	1	-

Amyloid biomarkers

12 endpoints

Secondary/protocol endpoint

Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)

Time frame:Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII

event count, event

Secondary/protocol endpoint

Change in Cerebrospinal Fluid (CSF) Levels of Amyloid Beta 40 (Aβ40)

Time frame:Baseline to last assessment

change from baseline, improvement

Secondary/protocol endpoint

Change in Cerebrospinal Fluid (CSF) Levels of Amyloid Beta 42 (Aβ42)

Time frame:Baseline to last assessment

change from baseline, improvement

Secondary/protocol endpoint

Cohort I : Annualized Change in Amyloid Deposition as Measured by Centiloids of Positron Emission Tomography (PET) Scan With Amyloid Radiotracer

Time frame:Baseline up to approximately Week 104

Amyloid PET Centiloid

change from baseline, improvement

Secondary/protocol endpoint

Cohort I: Peak Concentration (Cmax) of CAD106 Induced Abeta-specific Antibody Titers

Time frame:Week 9, 13, 15, 26 and quarterly thereafter (trough values)

concentration, descriptive

Secondary/protocol endpoint

Cohort I: Area Under the Concentration Curve (AUC) of CAD106 Induced Abeta-specific Antibody Titers

Time frame:Week 9, 13, 15, 26 and quarterly thereafter (trough values)

concentration, descriptive

Secondary/registry result

Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)

Time frame:Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Cohort I (CI) CAD106Questionable presence of ARIA-En=42 Participants	0	-
Presence of ARIA-En=42 Participants	1	-
ARIA-E - If present, the worst Severity=moderaten=42 Participants	1	-
Presence of ARIA-H - >4 microhemorrhages (new hemosiderin deposits < 10 mm)n=42 Participants	2	-
White matter disease worsening: 1-3 increasen=42 Participants	0	-
White matter disease worsening: 4 - 8 increasen=42 Participants	0	-
White matter disease worsening > 8 increasen=42 Participants	0	-
Any other MRI abnormalitiesn=42 Participants	2	-
Cohort I (CI) CAD106 PlaceboQuestionable presence of ARIA-En=23 Participants	0	-
Presence of ARIA-En=23 Participants	0	-
ARIA-E - If present, the worst Severity=moderaten=23 Participants	0	-
Presence of ARIA-H - >4 microhemorrhages (new hemosiderin deposits < 10 mm)n=23 Participants	0	-
White matter disease worsening: 1-3 increasen=23 Participants	2	-
White matter disease worsening: 4 - 8 increasen=23 Participants	0	-
White matter disease worsening > 8 increasen=23 Participants	0	-
Any other MRI abnormalitiesn=23 Participants	1	-
Cohort II (CII) CNP520Questionable presence of ARIA-En=249 Participants	0	-
Presence of ARIA-En=249 Participants	0	-
ARIA-E - If present, the worst Severity=moderaten=249 Participants	0	-
Presence of ARIA-H - >4 microhemorrhages (new hemosiderin deposits < 10 mm)n=249 Participants	6	-
White matter disease worsening: 1-3 increasen=249 Participants	6	-
White matter disease worsening: 4 - 8 increasen=249 Participants	0	-
White matter disease worsening > 8 increasen=249 Participants	0	-
Any other MRI abnormalitiesn=249 Participants	0	-
Cohort II (CII) CNP520 PlaceboQuestionable presence of ARIA-En=163 Participants	1	-
Presence of ARIA-En=163 Participants	2	-
ARIA-E - If present, the worst Severity=moderaten=163 Participants	2	-
Presence of ARIA-H - >4 microhemorrhages (new hemosiderin deposits < 10 mm)n=163 Participants	2	-
White matter disease worsening: 1-3 increasen=163 Participants	1	-
White matter disease worsening: 4 - 8 increasen=163 Participants	0	-
White matter disease worsening > 8 increasen=163 Participants	0	-
Any other MRI abnormalitiesn=163 Participants	0	-

Secondary/registry result

Change in Cerebrospinal Fluid (CSF) Levels of Amyloid Beta 40 (Aβ40)

Time frame:Baseline to last assessment

change from baseline, improvement

Secondary/registry result

Change in Cerebrospinal Fluid (CSF) Levels of Amyloid Beta 42 (Aβ42)

Time frame:Baseline to last assessment

change from baseline, improvement

Secondary/registry result

Cohort I : Annualized Change in Amyloid Deposition as Measured by Centiloids of Positron Emission Tomography (PET) Scan With Amyloid Radiotracer

Time frame:Baseline up to approximately Week 104

Amyloid PET Centiloid

change from baseline, improvement

Posted result

Group	Value (mean), Centiloids	Standard deviation
Cohort I (CI) CAD106n=42 Participants	-0.911	5.6596
Cohort I (CI) CAD106 Placebon=23 Participants	8.367	6.6805

Secondary/registry result

Cohort I: Peak Concentration (Cmax) of CAD106 Induced Abeta-specific Antibody Titers

Time frame:Week 9, 13, 15, 26 and quarterly thereafter (trough values)

concentration, descriptive

Posted result

Group	Value (geometric_mean), Days x titer levels rel. to ref. serum	Reported bounds
Cohort I (CI) CAD106n=41 Participants	128.76	-99.05 - 167.37

Secondary/registry result

Cohort I: Area Under the Concentration Curve (AUC) of CAD106 Induced Abeta-specific Antibody Titers

Time frame:Week 9, 13, 15, 26 and quarterly thereafter (trough values)

concentration, descriptive

Posted result

Group	Value (geometric_mean), Days x titer levels rel. to ref. serum	Reported bounds
Cohort I (CI) CAD106n=42 Participants	34999.89	-22992.17 - 53278.68

Tau biomarkers

2 endpoints

Secondary/protocol endpoint

Change in Cerebrospinal Fluid (CSF) Levels of Total Tau and Phosphorylated Tau

Time frame:Baseline to last assessment

change from baseline, improvement

Secondary/registry result

Change in Cerebrospinal Fluid (CSF) Levels of Total Tau and Phosphorylated Tau

Time frame:Baseline to last assessment

change from baseline, improvement

Neurodegeneration biomarkers

2 endpoints

Secondary/protocol endpoint

Change in Serum Neurofilaments

Time frame:Baseline to Week 26 and week 52, CI baseline to last assessment. CII baseline to last on-treatment and to last off-treatment

Neurofilament light (NfL)

change from baseline, improvement

Secondary/registry result

Change in Serum Neurofilaments

Time frame:Baseline to Week 26 and week 52, CI baseline to last assessment. CII baseline to last on-treatment and to last off-treatment

Neurofilament light (NfL)

change from baseline, improvement

Posted result

Group	Value (mean), pg/mL	Standard deviation
Cohort I (CI) CAD106Week 26n=20 Participants	1.44	3.165
Week 52n=8 Participants	2.63	5.716
C I Last post baseline assessmentn=20 Participants	1.77	4.643
Cohort I (CI) CAD106 PlaceboWeek 26n=10 Participants	-3.89	13.058
Week 52n=6 Participants	-6.09	16.542
C I Last post baseline assessmentn=10 Participants	-3.31	12.858
Cohort II (CII) CNP520Week 26n=72 Participants	0.644	3.4879
Week 52n=8 Participants	1.921	4.0515
C II Last on-treatmentn=72 Participants	0.647	3.5357
C II Last off-treatmentn=2 Participants	-0.004	3.7102
Cohort II (CII) CNP520 PlaceboWeek 26n=53 Participants	0.362	6.7547
Week 52n=9 Participants	-4.852	14.2270
C II Last on-treatmentn=51 Participants	0.280	6.8289
C II Last off-treatmentn=2 Participants	-2.145	2.6799

Neuroimaging

4 endpoints

Secondary/protocol endpoint

Annualized Percent Change on Volume of Brain Regions

Time frame:CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment

percent change from baseline, improvement

Secondary/protocol endpoint

Change in Neurofibrillary Tangle Burden as Measured by Standardized Uptake Ratio (SUVR) of PET Scans With Tau Radiotracer (Where Available)

Time frame:Baseline to last assessment

change from baseline, improvement

Secondary/registry result

Annualized Percent Change on Volume of Brain Regions

Time frame:CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage of volume change	Standard deviation
Cohort I (CI) CAD106WB Week 26n=35 Participants	-0.7570	1.33114
WB Week 52n=37 Participants	-0.5144	0.66578
WB CI Last post baseline assessmentn=40 Participants	-0.4645	0.57503
Hip Week 26n=35 Participants	-1.3262	2.35453
Hip Week 52n=37 Participants	-1.0376	1.44310
Hip CI Last post baseline assessmentn=40 Participants	-1.0801	1.38061
LV Week 26n=35 Participants	4.1848	5.77286
LV Week 52n=37 Participants	4.2060	3.92877
LV CI Last post baseline assessmentn=40 Participants	4.0543	3.75310
Cohort I (CI) CAD106 PlaceboWB Week 26n=23 Participants	-0.6044	1.29608
WB Week 52n=22 Participants	-0.3395	0.75810
WB CI Last post baseline assessmentn=23 Participants	-0.5321	0.46526
Hip Week 26n=23 Participants	-0.9245	2.81731
Hip Week 52n=22 Participants	-0.7780	1.81604
Hip CI Last post baseline assessmentn=23 Participants	-1.0477	1.33603
LV Week 26n=23 Participants	2.5581	7.54667
LV Week 52n=22 Participants	2.8232	5.04358
LV CI Last post baseline assessmentn=23 Participants	3.5427	3.53772
Cohort II (CII) CNP520WB Week 26n=145 Participants	-0.9318	1.06843
WB Week 52n=63 Participants	-0.6590	0.64838
WB CII Last on-treatmentn=148 Participants	-0.8268	0.94889
WB CII Last off-treatmentn=36 Participants	-0.6748	0.62542
Hip Week 26n=145 Participants	-1.6603	2.65529
Hip Week 52n=63 Participants	-1.2438	1.79988
Hip CII Last on-treatmentn=148 Participants	-1.4790	2.36526
Hip CII Last off-treatmentn=36 Participants	-1.9375	2.03593
LV Week 26n=145 Participants	4.5176	5.59748
LV Week 52n=63 Participants	3.3854	3.71214
LV CII Last on-treatmentn=148 Participants	4.3588	5.07839
LV CII Last off-treatmentn=36 Participants	3.9617	2.61831
Cohort II (CII) CNP520 PlaceboWB Week 26n=104 Participants	-0.4616	1.00537
WB Week 52n=40 Participants	-0.4227	0.58778
WB CII Last on-treatmentn=108 Participants	-0.5181	0.92086
WB CII Last off-treatmentn=23 Participants	-0.3317	0.62616
Hip Week 26n=104 Participants	-0.8817	2.06227
Hip Week 52n=40 Participants	-0.9567	1.42941
Hip CII Last on-treatmentn=108 Participants	-0.9984	1.85655
Hip CII Last off-treatmentn=23 Participants	-1.0498	1.66596
LV Week 26n=104 Participants	3.9735	4.23237
LV Week 52n=40 Participants	2.9059	3.18734
LV CII Last on-treatmentn=108 Participants	4.0308	3.64102
LV CII Last off-treatmentn=23 Participants	2.6052	3.54903

Secondary/registry result

Change in Neurofibrillary Tangle Burden as Measured by Standardized Uptake Ratio (SUVR) of PET Scans With Tau Radiotracer (Where Available)

Time frame:Baseline to last assessment

change from baseline, improvement

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

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