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A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (Generation S2)

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ClinicalTrials.gov Identifier: NCT03131453
Recruitment Status : Recruiting
First Posted : April 27, 2017
Last Update Posted : May 7, 2018
Sponsor:
Collaborators:
Amgen
Banner Alzheimer's Institute
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is to determine the effects of CNP520 on cognition, global clinical status, and underlying AD pathology, as well as the safety of CNP520, in people at risk for the onset of clinical symptoms of AD based on their age, APOE genotype and elevated amyloid.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: CNP520 50mg Drug: CNP520 15mg Other: Placebo to CNP520 Phase 2 Phase 3

Detailed Description:

The study uses a randomized, double-blind, placebo-controlled, parallel group, adaptive design with variable treatment duration in approximately 2000 cognitively unimpaired participants aged 60 to 75 years, with at least one APOE4 allele (Homozygotes or Heterozygotes) and, if Heterozygotes, with evidence of elevated brain amyloid.

The screening period is expected to last about 12 weeks. Participants will receive disclosure of their individual test results for APOE genotyping and brain amyloid status.

Treatment duration is variable (event driven trial) for at least 60 months, and up to an expected maximum of 84 months.

Participants will return to the study site every three months for drug dispensing and every six months for safety and efficacy assessments, including neuropsychological scales with input from the study partner. Brain MRI scans will be conducted at month 6 and month 12, and on a yearly basis thereafter.

The Follow-up visit will be scheduled 12 weeks after the end of the Treatment Epoch. An additional CSF and / or PET AD biomarker assessments will be conducted on a voluntary basis at year 2 and 5.

The study (also known as the Generation Study 2) is conducted as part of the Alzheimer's Prevention Initiative (API) program.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2000 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, Parallel Group Study to Evaluate the Efficacy and Safety of CNP520 in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (AD).
Actual Study Start Date : February 14, 2014
Estimated Primary Completion Date : July 30, 2024
Estimated Study Completion Date : August 30, 2024

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Arm#1: CNP520 50 mg
CNP520 50 mg capsule given p.o.
Drug: CNP520 50mg
Arm#1
Other Name: CNP520 50 mg capsule p.o. for the duration of the Treatment Epoch
Experimental: Arm#2: CNP520 15 mg
CNP520 15 mg capsule given p.o.
Drug: CNP520 15mg
Arm#2
Other Name: CNP520 15 mg capsule p.o. for the duration of Treatment Epoch
Placebo Comparator: Arm#3: Placebo
Placebo to CNP520 capsule given p.o.
Other: Placebo to CNP520
Arm#3
Other Name: Placebo to CNP520 p.o. for the duration of Treatment Epoch



Primary Outcome Measures :
  1. Time to event [ Time Frame: Through study completion, at least 5 years ]
    Event is defined as diagnosis of MCI due to AD or dementia due to AD, whichever occurs first during the course of the study, after confirmation by the 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 demonstrate the effects of CNP520, vs. placebo on global clinical status

  2. 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 demonstrate the effects of CNP520, vs. placebo on cognition

  3. Change in the Everyday Cognition scale (ECog) total scores [ Time Frame: Baseline to Month 60 ]
    To demonstrate the effects of CNP520, vs. placebo on function reported by the participant and study partner, respectively

  4. Change in cerebral amyloid angiopathy (CAA) [ Time Frame: Through study completion, at least 5 years ]
    To demonstrate the effects of CNP520 vs placebo on CAA, as measured by Magnetic Resonance Imaging (MRI)

  5. Change on volume of brain regions [ Time Frame: Baseline to Month 60 ]
    To demonstrate the effects of CNP520 vs placebo on brain atrophy, as measured by volumetric Magnetic Resonance Imaging (MRI)

  6. Change in amyloid deposition as measured by standardized uptake ratio (SUVR) of positron emission tomography (PET) scan with amyloid radiotracer [ Time Frame: Baseline to Months 24 and 60 ]
    To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers

  7. Change in CSF levels of Aβ40, Aβ42 [ Time Frame: Baseline to Months 24 and 60 ]
    To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers

  8. Change in CSF levels of total tau and phosphorylated tau [ Time Frame: Baseline to Months 24 and 60 ]
    To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers

  9. Number of participants with adverse events as a measure of safety [ Time Frame: Through study completion, at least 5 years ]
    To demonstrate the safety and tolerability of CNP520 vs placebo

  10. Change in neurofibrillary tangle burden as measured by standardized uptake ratio (SUVR) of PET scans with tau radiotracer (where available) [ Time Frame: Baseline to Months 24 and 60 ]
    To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers



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
Criteria

Inclusion Criteria:

  • consent to receive disclosure of their risk estimates to develop clinical symptoms of AD based on their APOE genotype and, if Heterozygotes, evidence of elevated brain amyloid.
  • Male or female, age 60 to 75 years inclusive. Females must be considered post-menopausal and not of child bearing potential
  • Cognitively unimpaired as evaluated by memory tests performed at screening.
  • Participant's willingness to have a study partner.
  • Carrier of at least one APOE4 gene if Heterozygotes, elevated brain amyloid (as measured by CSF Abeta or amyloid PET imaging).

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.
  • Indication for, or current treatment with ChEIs and/or another AD treatment (e.g. memantine).
  • Contraindication or intolerance to MRI.
  • 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, not as a result of a temporary condition.
  • Current clinically significant ECG findings.
  • Clinically relevant depigmenting or hypopigmenting conditions (e.g. albinism, vitiligo) or active / history of chronic urticaria 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): NCT03131453


Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 info@generationprogram.com

  Hide Study Locations
Locations
United States, Arizona
Banner Alzheimer's Institute, 901 East Willetta Street Recruiting
Phoenix, Arizona, United States, 85006
Contact    602-839-6230    Kinal.bhatt@bannerhealth.com   
Novartis Investigative Site Recruiting
Scottsdale, Arizona, United States, 85259
Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Building B Recruiting
Sun City, Arizona, United States, 85351
Contact    623-832-6590    nadira.trncic@bannerhealth.com   
Novartis Investigative Site Recruiting
Tucson, Arizona, United States, 85724
United States, California
ATP Clinical Research Inc, 3151 Airway Avenue T 3 Recruiting
Costa Mesa, California, United States, 92626
Contact    714-277-4472    bshih@theatpgroup.net   
Irvine Center for Clinical Res, 2515 McCabe Way Recruiting
Irvine, California, United States, 92618
Contact    949-753-1663 ext 208    tara@irvineclinical.com   
Torrance Clinical Research Institute, 25043 Narbonne Avenue Recruiting
Lomita, California, United States, 90717
Contact    310-373-8120    jgarcia.010186@gmail.com   
Novartis Investigative Site Recruiting
Oxnard, California, United States, 93030
Novartis Investigative Site Recruiting
San Diego, California, United States, 92103
Syrentis Clinical Research, 1401 N Tustin Ave, Suite 130 Recruiting
Santa Ana, California, United States, 92705
Contact    714-542-3008 ext 310    lorriebisesiphd@gmail.com   
Novartis Investigative Site Recruiting
Sebastopol, California, United States, 95472
United States, Colorado
Mountain Neurological Research, 350 Market Street, Suite 316 Recruiting
Basalt, Colorado, United States, 81621
Contact    970-927-1141    rosie@roaringforkneurology.com   
Colorado Springs Neurological, 2312 North Nevada Avenue, Suite 100 Recruiting
Colorado Springs, Colorado, United States, 80907
Contact    719-389-1129    adeschaine711@gmail.com   
Denver Neurological Clinic, 950 E Harvard Ave Not yet recruiting
Denver, Colorado, United States, 80210
Contact    303-715-9024    Susie@Denverneuroresearch.com   
United States, Connecticut
Yale University, One Church Street, Suite 600 Recruiting
New Haven, Connecticut, United States, 06519
Contact    203-764-8111    emily.kemp@yale.edu   
United States, District of Columbia
Novartis Investigative Site Recruiting
Washington, District of Columbia, United States, 20057
United States, Florida
Quantum Laboratories Recruiting
Deerfield Beach, Florida, United States, 33064
Contact    954-786-7331    quantmres2@aol.com   
Brain Matters Research, Inc., 800 NW 17th Avenue Recruiting
Delray Beach, Florida, United States, 33445
Contact    561-374-8461    afuquay@brainmattersresearch.com   
Infinity Clinical Research LLC, 4925 Sheridan Street, Suite 200 Recruiting
Hollywood, Florida, United States, 33021
Contact    706-455-1220    jriveros@infinityclinicalresearch.com   
Alzheimer39s Research and Trea, 5065 State Road , Suite 102 Recruiting
Lake Worth, Florida, United States, 33449
Contact    561-209-2400    dwatson@researchalz.com   
Meridien Research, 2300 Maitland center, Pkwy Ste 230 Recruiting
Maitland, Florida, United States, 32751
Contact    407-644-1165    amarraffino@meridienresearch.net   
Novartis Investigative Site Recruiting
Melbourne, Florida, United States, 32940
Novartis Investigative Site Recruiting
Merritt Island, Florida, United States, 32952
Novartis Investigative Site Recruiting
Miami, Florida, United States, 33032
New Horizon Research Center, 11880 SW 40 St., Suite 405 Recruiting
Miami, Florida, United States, 33175
Contact    305-226-3933    juliom@nhorizonresearch.com   
Miami-Dade Medical Research, 8955 SW 87 CT, Suite 112 Recruiting
Miami, Florida, United States, 33176
Contact    305-722-7210    ravellana@miamimedresearch.com   
Compass Research, LLC,100 West Gore Street, Suite 202 Recruiting
Orlando, Florida, United States, 32806
Contact    407-426-9299    Amy.edridge@Bioclinica.com   
Novartis Investigative Site Recruiting
Orlando, Florida, United States, 32806
Novartis Investigative Site Recruiting
Ormond Beach, Florida, United States, 32174
Novartis Investigative Site Recruiting
Palm Beach Gardens, Florida, United States, 33410
Novartis Investigative Site Recruiting
Port Orange, Florida, United States, 32127
Roskamp Institute, Inc., 2040 Whitfield Avenue Recruiting
Sarasota, Florida, United States, 34243
Contact    941-256-8018    dyildirim@roskampinstitute.net   
Novartis Investigative Site Recruiting
West Palm Beach, Florida, United States, 33407
United States, Georgia
Novartis Investigative Site Recruiting
Atlanta, Georgia, United States, 30322
Novartis Investigative Site Recruiting
Decatur, Georgia, United States, 30033
United States, Hawaii
Hawaii Pacific Neuroscience, 2230 Liliha st 104 Recruiting
Honolulu, Hawaii, United States, 96817
Contact    808-261-4476    research@hawaiineuroscience.com   
United States, Idaho
Advanced Clinical Research, 2950 E Magic View Dr, Suite 182 Recruiting
Meridian, Idaho, United States, 83642
Contact    208-377-8653    kwalk@acr-research.com   
United States, Illinois
Novartis Investigative Site Recruiting
Chicago, Illinois, United States, 60612
Novartis Investigative Site Recruiting
Chicago, Illinois, United States, 60640
Alexian Brothers Neuroscience, 800 Biesterfield Rd, Neuroscience Institute Brock Recruiting
Elk Grove Village, Illinois, United States, 60007
Contact    847-981-3645    Carolyn.ferrari@amitahealth.org   
United States, Kansas
Novartis Investigative Site Recruiting
Fairway, Kansas, United States, 66205
United States, Michigan
QUEST Research Institute, 28595 Orchard Lake Road, Suite 301 Recruiting
Farmington Hills, Michigan, United States, 48334
Contact    248-957-8940    mbelkin@mindonline.com   
United States, Minnesota
Novartis Investigative Site Recruiting
Rochester, Minnesota, United States, 55905
United States, Mississippi
Hattiesburg Clinic, 415 South 28th Avenue Recruiting
Hattiesburg, Mississippi, United States, 39401
Contact    601-579-5016    Kayleigh.Moring@hattiesburgclinic.com   
United States, New Jersey
Novartis Investigative Site Recruiting
West Long Branch, New Jersey, United States, 07764
United States, New Mexico
Albuquerque Neuroscience, 101 Hospital Loop ne, 209 209 Recruiting
Albuquerque, New Mexico, United States, 87109
Contact    505-848-3773    Andy@albneuro.com   
United States, New York
Novartis Investigative Site Recruiting
Brooklyn, New York, United States, 11235
Novartis Investigative Site Recruiting
Latham, New York, United States, 12110
NYU Langone Medical Center, 145 East 32nd Street, 2nd Floor, Room 226 Recruiting
New York, New York, United States, 10016
Contact    212-263-5845    Shannon.chen@nyumc.org   
Novartis Investigative Site Recruiting
Rochester, New York, United States, 14642
United States, North Carolina
ANI Neurology, PLLC dba Alzhe, 7809 Sardis Road Not yet recruiting
Charlotte, North Carolina, United States, 28270
Contact    704-364-4005    sbolouri@amcneurology.com   
Novartis Investigative Site Recruiting
Durham, North Carolina, United States, 27710
Novartis Investigative Site Recruiting
Greensboro, North Carolina, United States, 27410
United States, Oklahoma
Tulsa Clinical Research LLC, 1705 E 19th ST., STE 406/408 Recruiting
Tulsa, Oklahoma, United States, 74104
Contact    918-743-2349    ctoegel@tulsaclinicalresearch.com   
United States, Oregon
Summit Research Network, 2701 NW Vaughn St, Suite 350 Recruiting
Portland, Oregon, United States, 97210
Contact    503-293-5039 ext 17    afeldman@summitnetwork.com   
United States, Pennsylvania
Abington Neurological Associate Ltd., 2325 Maryland Road, Suite 100 Recruiting
Willow Grove, Pennsylvania, United States, 19090
Contact    215-957-9250    denisegallagher.ana@gmail.com   
United States, Rhode Island
Rhode Island Hospital and Memory Research Institute, 1018 Waterman Ave Recruiting
East Providence, Rhode Island, United States, 02914
Contact    401-435-8950    lgiven@rimmri.com   
Butler Hospital, 345 Blackstone Blvd. Recruiting
Providence, Rhode Island, United States, 02906
Contact    401-455-6211    lothompson@butler.org   
United States, South Carolina
Roper Hospital, 316 Calhoun Street 5th Floor Recruiting
Charleston, South Carolina, United States, 29401
Contact    843-724-2302    ric.freeman@rsfh.com   
United States, Texas
Novartis Investigative Site Recruiting
Austin, Texas, United States, 78757
Novartis Investigative Site Recruiting
Houston, Texas, United States, 77054
Novartis Investigative Site Recruiting
San Antonio, Texas, United States, 78229
United States, Washington
Novartis Investigative Site Withdrawn
Tacoma, Washington, United States, 98405
United States, Wisconsin
Novartis Investigative Site Withdrawn
Middleton, Wisconsin, United States, 53562
Belgium
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
Canada, Ontario
Toronto Memory Program, 1 Valleybrook Drive Suite 400 Not yet recruiting
Toronto, Ontario, Canada, M3B 2S7
Contact    1 416 386 9761    sramotar@memorydisorders.ca   
Finland
Novartis Investigative Site Recruiting
Kuopio, Finland, 70210
Novartis Investigative Site Recruiting
Turku, Finland, 20520
Iceland
Novartis Investigative Site Recruiting
Reykjavik, Iceland, IS-101
Japan
Ehime University Hospital, Shitsukawa Recruiting
Tōon, Ehime, Japan, 791-0295
Contact    81 89 964 5111    semba.makiko.ah@ehime-u.ac.jp   
Puerto Rico
Inspira Clinical Research, Ave Hostos 405 Not yet recruiting
San Juan, Puerto Rico, 00918
Contact    1 787 753 9515    estudio@inspirapr.com   
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 308433
Spain
Novartis Investigative Site Recruiting
Barcelona, Spain, 08005
Switzerland
Novartis Investigative Site Recruiting
Basel, CH, Switzerland, 4002
Novartis Investigative Site Recruiting
Lausanne, Switzerland, CH-1011
Sponsors and Collaborators
Novartis Pharmaceuticals
Amgen
Banner Alzheimer's Institute
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Additional Information:
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03131453     History of Changes
Other Study ID Numbers: CCNP520A2202J
2016-002976-28 ( EudraCT Number )
First Posted: April 27, 2017    Key Record Dates
Last Update Posted: May 7, 2018
Last Verified: May 2018
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

URL: http://

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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Placebo controlled,
APOE4 carriers,
Homozygotes,
Heterozygotes,
Brain Amyloid,
Preclinical Alzheimer's Disease (AD),
Aβ lowering,
BACE-1 inhibitor

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