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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)

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: NCT02565511
Recruitment Status : Active, not recruiting
First Posted : October 1, 2015
Last Update Posted : July 17, 2019
Sponsor:
Collaborators:
Banner Alzheimer's Institute
National Institute on Aging (NIA)
Alzheimer's Association
Amgen
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 one PET scan during the course of the study. Additional PET scans, blood and CSF collection will be voluntary. The study (also known as the Generation Study 1) is conducted as part of the Alzheimer's Prevention Initiative (API) program.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 481 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 : August 30, 2024
Estimated Study Completion Date : March 31, 2025

Resource links provided by the National Library of Medicine


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 self-reported Columbia Suicide Severity Rating Scale (eC-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 and tau tracer obtained using brain positron emission tomography (PET) imaging, volumetric MRI measurements, and CSF/blood Aβ40, Aβ42, total tau and phosphorylated tau181 and NFL levels.


  6. Change in APCC Test Score [ 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

  7. Change in 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 CDR-SOB.

  8. Aβ-specific immune response [ Time Frame: Through study completion, an average of 5 years ]
    To describe serological immune response to CAD106 injections as measured by Aβ-specific antibody titers generated



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Key Inclusion Criteria:

  • Consent 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 must be considered post-menopausal and not of child bearing potential.
  • Mini-Mental State Examination (MMSE) total score ≥ 24 (at screening or in previous 3 months) and cognitively unimpaired as evaluated by memory tests performed at screening.
  • Homozygous APOE4 genotype.
  • Participant's willingness to have a study partner.

Key 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 future 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, 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.


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


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Locations
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United States, Arizona
Banner Alzheimer's Institute
Phoenix, Arizona, United States, 85006
Novartis Investigative Site
Phoenix, Arizona, United States, 85006
Novartis Investigative Site
Scottsdale, Arizona, United States, 85259
Banner Sun City Research Institute
Sun City, Arizona, United States, 85351
United States, California
ATP Clinical Research, Inc.
Costa Mesa, California, United States, 92626
Irvine Center for Clinical Research
Irvine, California, United States, 92614
University of Southern California Keck School of Medicine Alzheimer Disease Research Center
Los Angeles, California, United States, 90033
Novartis Investigative Site
Palo Alto, California, United States, 94304
Novartis Investigative Site
San Diego, California, United States, 92103
Syrentis Clinical Research
Santa Ana, California, United States, 92705
Novartis Investigative Site
Sebastopol, California, United States, 95472
California Neuroscience Research Medical Group, Inc.
Sherman Oaks, California, United States, 91316
United States, Colorado
Mountain Neurological Research Center
Basalt, Colorado, United States, 81621
United States, Connecticut
Yale University Alzheimer's Disease Research Unit
New Haven, Connecticut, United States, 06510
New England Institute for Clinical Research
Stamford, Connecticut, United States, 06905
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20057
Novartis Investigative Site
Washington, District of Columbia, United States, 20059
United States, Florida
JEM Research Institute
Atlantis, Florida, United States, 33462-6608
Florida Atlantic University, Clinical Translational Research Unit
Boca Raton, Florida, United States, 33431
Brain Matters Research
Delray Beach, Florida, United States, 33445
Mayo Clinic Jacksonville
Jacksonville, Florida, United States, 32224
Meridien Research
Maitland, Florida, United States, 32751
Merritt Island Medical Research
Merritt Island, Florida, United States, 32952
Mount Sinai Medical Center - The Wien Center
Miami Beach, Florida, United States, 33140
University of Miami
Miami, Florida, United States, 33136
Compass Research
Orlando, Florida, United States, 32812
Progressive Medical Research
Port Orange, Florida, United States, 32127
USF Health Byrd Alzheimer's Institute
Tampa, Florida, United States, 33613
United States, Georgia
Novartis Investigative Site
Atlanta, Georgia, United States, 30322
Medical Research & Health Education Foundation, Inc.
Columbus, Georgia, United States, 31909
NeuroStudies
Decatur, Georgia, United States, 30033
United States, Idaho
Advanced Clinical Research
Meridian, Idaho, United States, 83642
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
Great Lakes Clinical Trials
Chicago, Illinois, United States, 60640
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Kansas
University of Kansas Alzheimer's Disease Center
Fairway, Kansas, United States, 66205
Via Christi Research
Wichita, Kansas, United States, 67214
United States, Kentucky
Sanders Brown Center on Aging, University of Kentucky
Lexington, Kentucky, United States, 40504
United States, Maine
Northern Light Acadia Hospital
Bangor, Maine, United States, 04401
United States, Massachusetts
Brigham & Women's Hospital Center for Alzheimer Research and Treatment
Boston, Massachusetts, United States, 01801
Novartis Investigative Site
Boston, Massachusetts, United States, 02115
Boston University Alzheimer's Disease Center
Boston, Massachusetts, United States, 02118
United States, Michigan
Novartis Investigative Site
Kalamazoo, Michigan, United States, 49008
United States, Minnesota
Novartis Investigative Site
Rochester, Minnesota, United States, 55905
Novartis Investigative Site
Saint Paul, Minnesota, United States, 55130
United States, Missouri
Saint Louis University Department of Psychiatry
Saint Louis, Missouri, United States, 63104
United States, Nebraska
Memory Disorders Program, Department of Neurological Sciences, University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-7680
United States, Nevada
Cleveland Clinic Lou Ruvo Center for Brain Health
Las Vegas, Nevada, United States, 89106
United States, New Jersey
Memory Enhancement Center
Eatontown, New Jersey, United States, 07724
United States, New York
The Memory Center of Northeastern New York
Latham, New York, United States, 12110
NYU Langone Medical Center
New York, New York, United States, 10016
The Nathan S. Kline Institute
Orangeburg, New York, United States, 10962
University of Rochester Medical Center
Rochester, New York, United States, 14620
United States, North Carolina
Alzheimer's Memory Center
Charlotte, North Carolina, United States, 28270
Duke University Medical center
Durham, North Carolina, United States, 27705
Triad Clinical Trials, LLC
Greensboro, North Carolina, United States, 27410
United States, Ohio
University Hospitals Cleveland Medical Center / Case Western Reserve University
Beachwood, Ohio, United States, 44122
Dayton Center for Neurological Disorders
Centerville, Ohio, United States, 45459
The Ohio State University
Columbus, Ohio, United States, 43210
United States, Oklahoma
IPS Research Company
Oklahoma City, Oklahoma, United States, 73103
Sooner Clinical Research
Oklahoma City, Oklahoma, United States, 73112
United States, Oregon
Memory Health Center at Summit Research Network
Portland, Oregon, United States, 97210
United States, Pennsylvania
The Clinical Trial Center, LLC
Jenkintown, Pennsylvania, United States, 19046
Abington Neurological Associates
Willow Grove, Pennsylvania, United States, 19090
United States, Rhode Island
Butler Hospital Memory and Aging Program
Providence, Rhode Island, United States, 02906
United States, South Carolina
Roper St. Francis - CBRI
Charleston, South Carolina, United States, 29401
United States, Tennessee
Novartis Investigative Site
Knoxville, Tennessee, United States, 37920
CNS Healthcare
Memphis, Tennessee, United States, 38119
Vanderbilt Center for Cognitive Medicine
Nashville, Tennessee, United States, 37212
United States, Texas
Senior Adults Specialty Research
Austin, Texas, United States, 78757
Kerwin Research Center & Memory Care
Dallas, Texas, United States, 75231
Houston Methodist Hospital
Houston, Texas, United States, 77030
University of Texas Health Science Center, Houston
Houston, Texas, United States, 77054
Clinical Trial Network
Houston, Texas, United States, 77074
United States, Vermont
The Memory Clinic
Bennington, Vermont, United States, 05201
United States, Washington
Universal Research Group
Tacoma, Washington, United States, 98405
United States, Wisconsin
The Medical College of WI
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
Novartis Investigative Site
Darlinghurst, New South Wales, Australia, 2010
Australia, Victoria
Novartis Investigative Site
Heidelberg Heights, Victoria, Australia, 3081
Australia, Western Australia
Novartis Investigative Site
Nedlands, Western Australia, Australia, 6009
Belgium
Novartis Investigative Site
Gent, Belgium, 9000
Novartis Investigative Site
Leuven, Belgium, 3000
Canada, British Columbia
Okanagan Clinical Trials
Kelowna, British Columbia, Canada, V1Y1Z9
Canada, Nova Scota
Novartis Investigative Site
Kentville, Nova Scota, Canada, B4N 4K9
Canada, Nova Scotia
Novartis Investigative Site
Halifax, Nova Scotia, Canada, B3S 1M7
Canada, Ontario
Novartis Investigative Site
London, Ontario, Canada, N6C 0A7
Novartis Investigative Site
Ottawa, Ontario, Canada, K1G 1Z3
Toronto Memory Program
Toronto, Ontario, Canada, M3B 2S7
The Centre for Memory and Aging
Toronto, Ontario, Canada, M4G 3E8
Novartis Investigative Site
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Novartis Investigative Site
Gatineau, Quebec, Canada, J8T 8J1
Novartis Investigative Site
Montreal, Quebec, Canada, H3A 2BA
Novartis Investigative Site
Sherbrooke, Quebec, Canada, J1H 5N4
Novartis Investigative Site
Sherbrooke, Quebec, Canada, J1J 2G2
Canada
Novartis Investigative Site
Quebec, Canada, G1J 1Z4
Finland
Novartis Investigative Site
Turku, Finland, 20520
Germany
Novartis Investigative Site
Bayreuth, Germany, 95445
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Boblingen, Germany, 71032
Novartis Investigative Site
Bochum, Germany, 44791
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
Nuernberg, Germany, 90402
Novartis Investigative Site
Siegen, Germany, 57076
Novartis Investigative Site
Ulm, Germany, 89073
Novartis Investigative Site
Wenzenbach, Germany, 93173
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1081 GN
Spain
Novartis Investigative Site
Terrassa, Barcelona, Spain, 08221
Novartis Investigative Site
Pozuelo de Alarcon, Madrid, Spain, 28223
Novartis Investigative Site
Barcelona, Spain, 08005
Novartis Investigative Site
Barcelona, Spain, 08014
Novartis Investigative Site
Donostia-San Sebastian, Spain, 20009
Switzerland
Novartis Investigative Site
Basel, CH, Switzerland, 4002
Novartis Investigative Site
Lausanne, Switzerland, CH-1011
United Kingdom
Novartis Investigative Site
Westbruy On Trym, Bristol, United Kingdom, BS10 5NB
Novartis Investigative Site
Exeter, Devon, United Kingdom, EX2 5DW
Novartis Investigative Site
Plymouth, Devon, United Kingdom, PL6 8BT
Novartis Investigative Site
Guildford, Surrey, United Kingdom, GU27YD
Novartis Investigative Site
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, G20 0XA
Novartis Investigative Site
Glasgow, United Kingdom
Novartis Investigative Site
London, United Kingdom, SE5 8AD
Novartis Investigative Site
London, United Kingdom, W12 0HS
Novartis Investigative Site
London, United Kingdom, W1G 9JF
Novartis Investigative Site
London, United Kingdom, W2 1PG
Novartis Investigative Site
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Novartis Pharmaceuticals
Banner Alzheimer's Institute
National Institute on Aging (NIA)
Alzheimer's Association
Amgen
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Additional Information:
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02565511     History of Changes
Other Study ID Numbers: CAPI015A2201J
2015-002715-15 ( EudraCT Number )
1UF1AG046150-01 ( U.S. NIH Grant/Contract )
First Posted: October 1, 2015    Key Record Dates
Last Update Posted: July 17, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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


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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:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders