A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (GS1)

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.

The purpose of this study was to test whether two investigational drugs called CAD106 and CNP520, administered separately, could slow down the onset and progression of clinical symptoms associated with Alzheimer's disease (AD) in participants at the risk to develop clinical symptoms based on their age and genotype.

Study Overview

• Status: Terminated
• Conditions: Alzheimers Disease
• Intervention / Treatment: Biological: CAD106 Immunotherapy; Other: Alum; Other: Placebo to CAD106; Drug: CNP520; Other: Placebo to CNP520

Detailed Description

The study (also known as the Generation Study 1, GS1) was conducted as part of the Alzheimer's Prevention Initiative (API) program.

This trial was a randomized, double-blind, placebo-controlled, parallel group, adaptive design with variable treatment duration planned in cognitively unimpaired APOE4 homozygotes (HMs) aged 60 to 75 years. Participants were enrolled into Cohort I (CAD106) or Cohort II (CNP520).

The planned treatment period of 5 to 8 years was not achieved due to early study termination.

The study was terminated due to unexpected changes in cognitive function, brain volume loss, and body weight loss. Cohort II (CNP520) treatment was stopped and evaluated through an off-treatment follow-up period. After the decision to terminate Cohort II of the study (CNP520), treatment with CAD106 (Cohort I) was also terminated.

• Study Type: Interventional
• Enrollment (Actual): 480
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Novartis Investigative Site
  • Victoria
    • Heidelberg Heights, Victoria, Australia, 3081
      • Novartis Investigative Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Novartis Investigative Site
• Belgium
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Canada
  • Quebec, Canada, G1J 1Z4
    • Novartis Investigative Site
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y1Z9
      • Okanagan Clinical Trials
  • Nova Scota
    • Kentville, Nova Scota, Canada, B4N 4K9
      • Novartis Investigative Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1M7
      • Novartis Investigative Site
  • Ontario
    • London, Ontario, Canada, N6C 0A7
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program
    • Toronto, Ontario, Canada, M4G 3E8
      • The Centre for Memory and Aging
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Novartis Investigative Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Novartis Investigative Site
    • Sherbrooke, Quebec, Canada, J1J 2G2
      • Novartis Investigative Site
• Finland
  • Turku, Finland, 20520
    • Novartis Investigative Site
• Germany
  • Bayreuth, Germany, 95445
    • Novartis Investigative Site
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Boblingen, Germany, 71032
    • Novartis Investigative Site
  • Gottingen, Germany, 37075
    • Novartis Investigative Site
  • Halle, Germany, 06120
    • Novartis Investigative Site
  • Kiel, Germany, 24105
    • Novartis Investigative Site
  • Koeln, Germany, 50937
    • Novartis Investigative Site
  • Leipzig, Germany, 04107
    • Novartis Investigative Site
  • Mannheim, Germany, 68159
    • Novartis Investigative Site
  • Münster, Germany, 48149
    • Novartis Investigative Site
  • Siegen, Germany, 57076
    • Novartis Investigative Site
  • Wenzenbach, Germany, 93173
    • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1081 GN
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08005
    • Novartis Investigative Site
  • Barcelona, Spain, 08014
    • Novartis Investigative Site
  • Donostia-San Sebastian, Spain, 20009
    • Novartis Investigative Site
  • Barcelona
    • Terrassa, Barcelona, Spain, 08221
      • Novartis Investigative Site
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Novartis Investigative Site
• Switzerland
  • CH
    • Basel, CH, Switzerland, 4002
      • Novartis Investigative Site
• United Kingdom
  • Avon, United Kingdom, BA1 3NG
    • Novartis Investigative Site
  • Birmingham, United Kingdom, B16 8QQ
    • Novartis Investigative Site
  • Dundee, United Kingdom, DD1 9SY
    • Novartis Investigative Site
  • Glasgow, United Kingdom
    • Novartis Investigative Site
  • Glasgow, United Kingdom, G20 0XA
    • Novartis Investigative Site
  • London, United Kingdom, W2 1NY
    • Novartis Investigative Site
  • London, United Kingdom, W12 0HS
    • Novartis Investigative Site
  • London, United Kingdom, SE5 8AD
    • Novartis Investigative Site
  • London, United Kingdom, W1G 9JF
    • Novartis Investigative Site
  • London, United Kingdom, W2 1PG
    • Novartis Investigative Site
  • Manchester, United Kingdom, M13 9WL
    • Novartis Investigative Site
  • Bristol
    • Westbruy On Trym, Bristol, United Kingdom, BS10 5NB
      • Novartis Investigative Site
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Novartis Investigative Site
    • Plymouth, Devon, United Kingdom, PL6 8BT
      • Novartis Investigative Site
  • Surrey
    • Guildford, Surrey, United Kingdom, GU27YD
      • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Phoenix, Arizona, United States, 85006
      • Novartis Investigative Site
    • Scottsdale, Arizona, United States, 85259
      • Novartis Investigative Site
    • Sun City, Arizona, United States, 85351
      • Banner Sun City Research Institute
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc.
    • Irvine, California, United States, 92614
      • Irvine Center for Clinical Research
    • Los Angeles, California, United States, 90033
      • University of Southern California Keck School of Medicine Alzheimer Disease Research Center
    • Palo Alto, California, United States, 94304
      • Novartis Investigative Site
    • San Diego, California, United States, 92103
      • Novartis Investigative Site
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
    • Sebastopol, California, United States, 95472
      • Novartis Investigative Site
    • Sherman Oaks, California, United States, 91316
      • California Neuroscience Research Medical Group, Inc.
    • Temecula, California, United States, 92591
      • Novartis Investigative Site
  • Colorado
    • Basalt, Colorado, United States, 81621
      • Novartis Investigative Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University Alzheimer's Disease Research Unit
    • Stamford, Connecticut, United States, 06905
      • New England Institute for Clinical Research
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Georgetown University
    • Washington, District of Columbia, United States, 20059
      • Novartis Investigative Site
  • Florida
    • Atlantis, Florida, United States, 33462-6608
      • JEM Research Institute
    • Boca Raton, Florida, United States, 33431
      • Florida Atlantic University, Clinical Translational Research Unit
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Jacksonville, Florida, United States, 32224
      • Novartis Investigative Site
    • Maitland, Florida, United States, 32751
      • Meridien Research
    • Merritt Island, Florida, United States, 32952
      • Merritt Island Medical Research
    • Miami, Florida, United States, 33136
      • University of Miami
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center - The Wien Center
    • Orlando, Florida, United States, 32806
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32812
      • Compass Research
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Tampa, Florida, United States, 33613
      • USF Health Byrd Alzheimer's Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Novartis Investigative Site
    • Columbus, Georgia, United States, 31909
      • Medical Research & Health Education Foundation, Inc.
    • Decatur, Georgia, United States, 30033
      • NeuroStudies
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Alzheimer's Disease Center
    • Wichita, Kansas, United States, 67214
      • Via Christi Research
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Sanders Brown Center on Aging, University of Kentucky
  • Maine
    • Bangor, Maine, United States, 04401
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Novartis Investigative Site
    • Boston, Massachusetts, United States, 02118
      • Novartis Investigative Site
  • Michigan
    • Kalamazoo, Michigan, United States, 49008
      • Novartis Investigative Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55130
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Novartis Investigative Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198-7680
      • Memory Disorders Program, Department of Neurological Sciences, University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo Center for Brain Health
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Center
  • New York
    • Latham, New York, United States, 12110
      • The Memory Center of Northeastern New York
    • New York, New York, United States, 10016
      • NYU Langone Medical Center
    • Orangeburg, New York, United States, 10962
      • The Nathan S. Kline Institute
    • Rochester, New York, United States, 14620
      • University of Rochester Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28270
      • Alzheimer's Memory Center
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
    • Greensboro, North Carolina, United States, 27410
      • Triad Clinical Trials, LLC
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • University Hospitals Cleveland Medical Center / Case Western Reserve University
    • Centerville, Ohio, United States, 45459
      • Novartis Investigative Site
    • Columbus, Ohio, United States, 43210
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • IPS Research Company
    • Oklahoma City, Oklahoma, United States, 73112
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97210
      • Memory Health Center at Summit Research Network
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • The Clinical Trial Center, LLC
    • Philadelphia, Pennsylvania, United States, 19104
      • Novartis Investigative Site
    • Willow Grove, Pennsylvania, United States, 19090
      • Abington Neurological Associates
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital Memory and Aging Program
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Roper St. Francis - CBRI
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Novartis Investigative Site
    • Memphis, Tennessee, United States, 38119
      • CNS Healthcare
    • Nashville, Tennessee, United States, 37212
      • Novartis Investigative Site
  • Texas
    • Austin, Texas, United States, 78757
      • Senior Adults Specialty Research
    • Dallas, Texas, United States, 75231
      • Kerwin Research Center & Memory Care
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77054
      • University of Texas Health Science Center, Houston
  • Vermont
    • Bennington, Vermont, United States, 05201
      • The Memory Clinic
  • Washington
    • Tacoma, Washington, United States, 98405
      • Universal Research Group
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • The Medical College of WI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Key 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort I (CAD106); CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter	Biological: CAD106 Immunotherapy; Participants will be given i.m. injections at Weeks 1, 7, 13 and quarterly i.m. injections (every 13 weeks) thereafter, until the last injection 3 month prior to completion of the Treatment Epoch.; Other: Alum; Alum was mixed with reconstituted CAD106 as adjuvant therapy to maximize the effectiveness of CAD106
Placebo Comparator: Cohort I (CAD106 Placebo); Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter	Other: Alum; Alum was mixed with reconstituted CAD106 as adjuvant therapy to maximize the effectiveness of CAD106; Other: Placebo to CAD106; Participants will be given i.m. injections at Weeks 1, 7, 13 and quarterly i.m. injections (every 13 weeks) thereafter, until the last injection 3 month prior to completion of the Treatment Epoch.
Experimental: Cohort II (CNP520); CNP520 (50 mg) capsules taken orally once daily	Drug: CNP520; CNP520 50 mg capsule p.o. for the duration of the Treatment Epoch.
Placebo Comparator: Cohort II (CNP520 Placebo); Matching Placebo to CNP520 capsules taken orally once daily	Other: Placebo to CNP520; Placebo to CNP520 p.o. for the duration of the Treatment Epoch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))	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.	Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII
Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score	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.	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 in the Total Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).	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.	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 in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).	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.	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 in the Everyday Cognition Scale (ECog-Subject) Total Scores	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.	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 in the Everyday Cognition Scale (ECog-Informant) Total Scores	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. Cohort I=C I and Cohort II=C II.	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
Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)	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 since baseline) and a general assessment of brain abnormalities. Assessment of cerebral amyloid angiopathy (CAA) is included in the overall safety MRI findings results.	Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII
Annualized Percent Change on Volume of Brain Regions	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.	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 in Cerebrospinal Fluid (CSF) Levels of Amyloid Beta 40 (Aβ40)	Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): Amyloid Beta 40 (Aβ40)	Baseline to last assessment
Change in Cerebrospinal Fluid (CSF) Levels of Amyloid Beta 42 (Aβ42)	Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): Amyloid Beta 42 (Aβ42)	Baseline to last assessment
Change in Cerebrospinal Fluid (CSF) Levels of Total Tau and Phosphorylated Tau	Alzheimer's Disease-related biomarkers analyzed in cerebrospinal fluid (CSF): total tau protein and phosphorylated tau protein levels	Baseline to last assessment
Change in Neurofibrillary Tangle Burden as Measured by Standardized Uptake Ratio (SUVR) of PET Scans With Tau Radiotracer (Where Available)	To demonstrate the effects of CNP520 vs placebo on tau pathology in the brain	Baseline to last assessment
Cohort I : Annualized Change in Amyloid Deposition as Measured by Centiloids of Positron Emission Tomography (PET) Scan With Amyloid Radiotracer	To demonstrate the effects of CAD106 vs placebo on Alzheimer's Disease-related biomarkers	Baseline up to approximately Week 104
Change in Serum Neurofilaments	Alzheimer's Disease-related biomarkers analyzed in blood serum: light chain neurofilaments (NfL)	Baseline to Week 26 and week 52, CI baseline to last assessment. CII baseline to last on-treatment and to last off-treatment
Number of Suicidal Ideation or Behavior Events	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.	Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII
Cohort I : Change in Cognition as Measured by APCC and CDR-SOB Scores and Antibody Response		Month 6 to Month 60
Cohort I: Peak Concentration (Cmax) of CAD106 Induced Abeta-specific Antibody Titers	Cmax is the maximum Titer Concentration of any post-baseline 'on treatment' visit. A visit is considered as 'on treatment' if visit date is within {last injection + 180 days}. - Geometric mean and CI's are back-transformed from the estimates for Log mean and CI's.	Week 9, 13, 15, 26 and quarterly thereafter (trough values)
Cohort I: Area Under the Concentration Curve (AUC) of CAD106 Induced Abeta-specific Antibody Titers	AUC is calculated based on 'on treatment' visit only.(missing values for peak visits were linearly interpolated for calculation; missing values for trough visits were imputed by average of non-missing trough values.).	Week 9, 13, 15, 26 and quarterly thereafter (trough values)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Collaborators: National Institute on Aging (NIA); Amgen; Banner Alzheimer's Institute

Publications and helpful links

Helpful Links

• Generation Program web site

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2015
• Primary Completion (Actual): April 30, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: September 28, 2015
• First Submitted That Met QC Criteria: September 29, 2015
• First Posted (Estimate): October 1, 2015

Study Record Updates

• Last Update Posted (Actual): July 8, 2021
• Last Update Submitted That Met QC Criteria: July 7, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: elderly; Prevention; Randomization; Placebo controlled; Brain Amyloid; Parallel-group; APOE4 Homozygotes; Preclinical Alzheimers Disease (AD); Aβ lowering; CNP520; CAD106; BACE-1 inhibitor; Unimpaired cognition
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; CNP520
• Other Study ID Numbers: CAPI015A2201J; 2015-002715-15 (EudraCT Number); 1UF1AG046150-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No