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A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (Generation S1)

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ClinicalTrials.gov Identifier: NCT02565511
Recruitment Status : Recruiting
First Posted : October 1, 2015
Last Update Posted : February 5, 2018
Banner Alzheimer's Institute
National Institute on Aging (NIA)
Alzheimer's Association
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is to test whether two investigational drugs called CAD106 and CNP520, administered separately, can 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.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Biological: CAD106 Immunotherapy Other: Placebo to CAD106 Drug: CNP520 Other: Placebo to CNP520 Phase 2 Phase 3

Detailed Description:

This study will assess the effects of each of the two therapies given separately, both targeting amyloid, on cognition, global clinical status, and underlying pathology in participants at risk for the onset of clinical symptoms of Alzheimer's disease (AD). Cognitively unimpaired individuals with two APOE4 genes and age 60 to 75 years, inclusive, are selected as they represent a population at particularly high risk of progression to Mild Cognitive Impairment and/or dementia due to Alzheimer's disease.

The study follows a randomized, double-blind, placebo-controlled, two-cohort, parallel group design in which participants receive one of the investigational treatments or their matching placebo for at least 60 months up to a maximum of 96 months and no longer than when the target number of events for the TTE endpoint has been observed and confirmed in either cohort.

An unbalanced randomization (active: placebo) of 5:3 ratio in Cohort I (430 CAD106 :260 Placebo) and 3:2 ratio in Cohort II (390 CNP520 : 260 Placebo) will be applied. Randomization will be stratified by age group (60-64 years, 65-75 years) and region (North America/Other , Europe).

Participants who meet study entry requirements will be required to undergo at least two PET scans during the course of the study. Additional PET scans, blood and CSF collection will be voluntary. The study (also known as the API APOE4 trial) is conducted as part of the Alzheimer's Prevention Initiative (API) program.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1340 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : November 30, 2015
Estimated Primary Completion Date : May 6, 2024
Estimated Study Completion Date : May 6, 2024

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Arm#1
CAD106 (450 µg) + Alum (450 µg) given i.m. at week 1, 7, 13 and quarterly 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.
Placebo Comparator: Arm#2
Placebo to CAD106 + Alum (450 µg) given i.m. at week 1, 7, 13 and quarterly thereafter
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: Arm#3
CNP520 (50 mg) capsules oral intake (p.o.)
Drug: CNP520
CNP520 50 mg capsule p.o. for the duration of the Treatment Epoch.
Placebo Comparator: Arm#4
Placebo to CNP520 capsules oral intake (p.o.)
Other: Placebo to CNP520
Placebo to CNP520 p.o. for the duration of the Treatment Epoch

Primary Outcome Measures :
  1. Time to diagnosis of MCI due to Alzheimer's Disease (AD) or dementia due to Alzheimer's Disease [ Time Frame: Through study completion, an average of 5 years ]
    Time when diagnosis is confirmed by adjudication committee

  2. Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score [ Time Frame: Baseline to Month 60 ]
    Composite score derived from the specific tests from the Repeatable Battery for the Assessment of Neurological Status (RBANS), Mini-Mental State Examination (MMSE), Raven's Progressive Matrices

Secondary Outcome Measures :
  1. Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score [ Time Frame: Baseline to Month 60 ]
    To assess the effects of CAD106 and CNP520, vs. respective placebo on global clinical status as measured by the change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score.

  2. Number of participants with Adverse Events as a measure of Safety and Tolerability [ Time Frame: Through study completion, an average of 5 years ]

    To assess the safety and tolerability of CAD106 and CNP520, vs. respective placebo by measured adverse events (AEs), and changes in the brain structural MRI, laboratory tests, non-cognitive neurological and psychiatric examinations including the Columbia Suicide Severity Rating Scale (C-SSRS), vital signs and electrocardiogram (ECG).

    Cohort - I: Injection-related reactions will also be analyzed. Cohort - II: Skin related AEs by regular skin examinations and centralized dermatological monitoring.

  3. Change on the Total Scale score and individual neurocognitive domain index scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: Baseline to Month 60 ]
    To assess the effects of CAD106 and CNP520, vs. respective placebo on cognition as measured by changes on the Total Scale score and individual neurocognitive domain index scores of the RBANS.

  4. Change in the Everyday Cognition scale (ECog) total scores [ Time Frame: Baseline to Month 60 ]
    To assess the effects of CAD106 and CNP520, vs. respective placebo on function as measured by the change in ECog total score reported by the participant and study partner, respectively.

  5. Change in Alzheimer's Disease related biomarkers [ Time Frame: Baseline to Months 24 and 60 ]

    To assess the effects of CAD106 and CNP520, vs. respective placebo on AD-related biomarkers (amyloid deposition and measures of neurodegeneration) as measured by changes on:

    amyloid tracer 18F-florbetapir obtained using brain positron emission tomography (PET) imaging, volumetric MRI measurements, and CSF Aβ40, Aβ42, total tau and phosphorylated tau181 levels.

  6. Change in APCC Test Score and CDR-SOB [ Time Frame: Month 6 to Month 60 ]
    To assess the effects of antibody response to CAD106 vs. placebo on cognition as measured by changes on the APCC test score and CDR-SOB.

  7. Aβ-specific immune response [ Time Frame: Through study completion, an average of 5 years ]
    To describe Aβ-specific antibody titers and serological responder rates as measured by peak concentration and area under the concentration curve (AUC) of antibody titers.

Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • Male or female, age 60 to 75 years inclusive. Females must be considered post-menopausal and not of child bearing potential.
  • Mini-Mental State Examination (MMSE) total score ≥ 24 and cognitively unimpaired as evaluated by memory tests performed at screening.
  • Homozygous APOE4 genotype.
  • Participant's willingness to have a study partner.

Exclusion Criteria:

  • Any disability that may prevent the participants from completing all study requirements.
  • Current medical or neurological condition that might impact cognition or performance on cognitive assessments.
  • Advanced, severe progressive or unstable disease that may interfere 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 the past 60 months.
  • History of hypersensitivity to any of the investigational drugs or their excipients / adjuvant or to drugs of similar chemical classes.
  • Indication for, or 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 might be a leading cause to cognitive decline, might pose a risk to the participant, or might prevent a satisfactory MRI assessment for safety monitoring.
  • Suicidal Ideation in the past six months, or Suicidal Behavior in the past two years.
  • A positive drug screen at Screening, if, in the Investigator's opinion, this is due to drug abuse.
  • Significantly abnormal laboratory results at Screening, not as a result of a temporary condition.
  • Current clinically significant ECG findings.

For Cohort - II only:

• Participants with depigmenting or hypopigmenting conditions (e.g. albinism vitiligo) or active / history of chronic urticarial in the past year.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02565511

Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: UBC Call Center 1-866-244-8907 info@generationprogram.com

  Hide Study Locations
United States, Arizona
Banner Alzheimer's Institute Recruiting
Phoenix, Arizona, United States, 85006
Contact    602-839-6500    roma.patel@bannerhealth.com   
Mayo Clinic Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact    480-301-6726    Thomas.martha1@mayo.edu   
Banner Sun City Research Institute Recruiting
Sun City, Arizona, United States, 85351
Contact    623-832-6500    bannerresearch@bannerhealth.com   
United States, California
ATP Clinical Research, Inc. Recruiting
Costa Mesa, California, United States, 92626
Contact    714-277-4472    info@atpcr.com   
Irvine Center for Clinical Research Recruiting
Irvine, California, United States, 92614
Contact    949-753-1663    studies@irvineclinical.com   
Syrentis Clinical Research Recruiting
Santa Ana, California, United States, 92705
Contact    714-542-3008    lorriebisesiphd@gmail.com   
California Neuroscience Research Medical Group, Inc. Recruiting
Sherman Oaks, California, United States, 91316
Contact    818-990-2671    marlene@cnrmg.com   
United States, Connecticut
Yale University Alzheimer's Disease Research Unit Recruiting
New Haven, Connecticut, United States, 06510
Contact    203-764-8100    Emily.kemp@yale.edu   
Contact    203-764-8145      
United States, District of Columbia
Georgetown University Recruiting
Washington, District of Columbia, United States, 20057
Contact    202-687-8800    mj582@georgetown.edu   
United States, Florida
Brain Matters Research Recruiting
Delray Beach, Florida, United States, 33445
Contact    561-381-9060    jlesmes@brainmattersresearch.com   
Mayo Clinic Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
Contact    904-953-8014    Walkermoore.kimpoki@mayo.edu   
Merritt Island Medical Research Recruiting
Merritt Island, Florida, United States, 32952
Contact    321-305-5015    info@mimresearch.com   
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact    305-355-9120    brobertson@med.miami.edu   
Compass Research Recruiting
Orlando, Florida, United States, 32812
Contact    407-210-1337    Jennifer.Trotter@Compass.Bioclinica.com   
United States, Georgia
Medical Research & Health Education Foundation, Inc. Recruiting
Columbus, Georgia, United States, 31909
Contact    706-653-8455    Research4@stork.md   
NeuroStudies Recruiting
Decatur, Georgia, United States, 30033
Contact    404-475-0552    jcavin@neurostudies.net   
United States, Idaho
Advanced Clinical Research Recruiting
Meridian, Idaho, United States, 83642
Contact    208-377-8653    kdellergo@acr-research.com   
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact    312-942-0050      
Great Lakes Clinical Trials Recruiting
Chicago, Illinois, United States, 60640
Contact    773-275-3500    info@greatlakesclinicaltrials.com   
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact    317-963-7440    aklaehn@iupui.edu   
United States, Kansas
University of Kansas Alzheimer's Disease Center Recruiting
Fairway, Kansas, United States, 66205
Contact    913-588-0555    kuamp@kumc.edu   
United States, Kentucky
Sanders Brown Center on Aging, University of Kentucky Recruiting
Lexington, Kentucky, United States, 40504
Contact    859-323-1331    shbardach@uky.edu   
United States, Massachusetts
Brigham & Women's Hospital Center for Alzheimer Research and Treatment Not yet recruiting
Boston, Massachusetts, United States, 01801
Contact    617-525-8383    mvandervliet@partners.org   
United States, Minnesota
Novartis Investigative Site Not yet recruiting
Rochester, Minnesota, United States, 55902
United States, Nebraska
Memory Disorders Program, Department of Neurological Sciences, University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198-7680
Contact    402-552-6233    rhogue@unmc.edu   
United States, Nevada
Cleveland Clinic Lou Ruvo Center for Brain Health Recruiting
Las Vegas, Nevada, United States, 89106
Contact    702-483-6026    brainhealth@ccf.org   
United States, New York
The memory Center of Northeastern New York Recruiting
Latham, New York, United States, 12110
Contact    518-785-1000    cfrazier@tristateneuro.com   
NYU Langone Medical Center Recruiting
New York, New York, United States, 10016
Contact    212-263-5845    Mrunalini.gaikwad@nyumc.org   
The Nathan S. Kline Institute Recruiting
Orangeburg, New York, United States, 10962
Contact    845-398-5582    Sameh.Nosir@nki.rfmh.org   
Contact    845-398-6532      
University of Rochester Medical Center Recruiting
Rochester, New York, United States, 14620
Contact    585-760-6562    Susan_salem-spencer@urmc.rochester.edu   
United States, North Carolina
Alzheimer's Memory Center Recruiting
Charlotte, North Carolina, United States, 28270
Contact    704-364-4000 ext 235    hswierc@amcneurology.com   
Duke University Medical center Recruiting
Durham, North Carolina, United States, 27705
Contact    919-668-2841    Jessica.carlson@duke.edu   
United States, Ohio
University Hospitals Cleveland Medical Center / Case Western Reserve University Recruiting
Beachwood, Ohio, United States, 44122
Contact    216-464-6474    parrianne.fatica@uhhospitals.org   
United States, Oregon
Memory Health Center at Summit Research Network Recruiting
Portland, Oregon, United States, 97210
Contact    503-228-2273    oregon@summitnetwork.com   
United States, Pennsylvania
Abington Neurological Associates Recruiting
Willow Grove, Pennsylvania, United States, 19090
Contact    215-957-9250    denisegallagher.ana@gmail.com   
United States, Rhode Island
Butler Hospital Memory and Aging Program Recruiting
Providence, Rhode Island, United States, 02906
Contact    401-455-6402    memory@butler.org   
United States, South Carolina
Roper St. Francis - CBRI Recruiting
Charleston, South Carolina, United States, 29401
Contact    843-724-2302    Allison.lapp@rsfh.com   
United States, Texas
Senior Adults Specialty Research Recruiting
Austin, Texas, United States, 78757
Contact    512-407-8628    mdraper@senioradults.net   
Clinical Trial Network Recruiting
Houston, Texas, United States, 77074
Contact    713-484-6947    mespiritu@ctntexas.com   
United States, Vermont
The Memory Clinic Recruiting
Bennington, Vermont, United States, 05201
Contact    802-447-1409    megan@memorydoc.org   
United States, Wisconsin
The Medical College of WI Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact    414-805-8328    bblaney@mcw.edu   
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
Canada, British Columbia
Okanagan Clinical Trials Recruiting
Kelowna, British Columbia, Canada, V1Y1Z9
Contact    250-862-8141    drchristie@oktrials.ca   
Canada, Ontario
Toronto Memory Program Recruiting
Toronto, Ontario, Canada, M3B 2S7
Contact    416-386-9606    research@memorydisorders.ca   
The Centre for Memory and Aging Recruiting
Totonto, Ontario, Canada, M4G 3E8
Contact    416-663-6897 ext 23    lcornejo@memorycentre.ca   
Canada, Quebec
Q&T Research Sherbrooke Recruiting
Sherbrooke, Quebec, Canada, J1J 2G2
Contact    819-562-6374    pierre.gervais@qtresearch.com   
Novartis Investigative Site Recruiting
Turku, Finland, 20520
Novartis Investigative Site Recruiting
Amsterdam, Netherlands, 1081 GN
Novartis Investigative Site Recruiting
Barcelona, Spain, 08005
Novartis Investigative Site Recruiting
Basel, CH, Switzerland, 4002
Novartis Investigative Site Recruiting
Lausanne, Switzerland, CH-1011
Sponsors and Collaborators
Novartis Pharmaceuticals
Banner Alzheimer's Institute
National Institute on Aging (NIA)
Alzheimer's Association

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02565511     History of Changes
Other Study ID Numbers: CAPI015A2201J
2015-002715-15 ( EudraCT Number )
First Posted: October 1, 2015    Key Record Dates
Last Update Posted: February 5, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Randomization, Placebo controlled, Parallel-group, APOE4 Homozygotes, Preclinical Alzheimer's Disease (AD), Aβ lowering

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders