Clinical trial NCT03131453: A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease
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).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Alzheimers Disease
Keywords: Placebo controlled
APOE4 carriers
Homozygotes
Heterozygotes
Brain Amyloid
Aβ lowering
BACE-1 inhibitor
CNP520
elderly
preclinical Alzheimers disease
Alzheimers Disease
Prevention
Unimpaired cognition
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Amgen
name: Banner Alzheimer's Institute
First posted: 2017-04-27
Enrollment: 1145
Sex: ALL
Minimum age (years): 60
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This trial was a randomized, double-blind, placebo-controlled, parallel group, adaptive design with variable treatment duration planned in cognitively unimpaired participants aged 60 to 75 years, with at least one apolipoprotein E allele (APOE4), (homozygotes (HMs) or heterozygotes (HTs)) and, if HTs, with evidence of elevated brain amyloid. The participants were randomized to either CNP520 50 mg, CNP520 15 mg or placebo a 2:1:2 ratio and was stratified based on amyloid status. The planned treatment period of 5 to 8 years was not achieved due to early study termination.

Eligibility 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 could have prevented the participants 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 could 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 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, could have posed a risk to the participant, or could have prevented 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, was 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.

Primary outcomes:
measure: Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))
timeFrame: Baseline to last cognitive assessment performed (up to day 648)
measure: Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
timeFrame: Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
Secondary outcomes:
measure: Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score
timeFrame: Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
measure: Change in the Total and Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
timeFrame: Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
measure: Change in the Everyday Cognition Scale (ECog-Subject) Total Scores
timeFrame: Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
measure: Change in the Everyday Cognition Scale (ECog-Informant) Total Scores
timeFrame: Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
measure: Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)
timeFrame: Baseline up to study termination approximately 617 days
measure: Annualized Percent Change on Volume of Brain Regions
timeFrame: Baseline to Week 26, Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
measure: Change in CSF Levels of Amyloid Beta 40 (Aβ40)
timeFrame: Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
measure: Change in CSF Levels of Amyloid Beta 42 (Aβ42)
timeFrame: Baseline to Last on-treatment (Day 547) and Baseline to Last off-treatment (Day 648)
measure: Change in Neurofibrillary Tangle Burden as Measured by Standardized Uptake Ratio (SUVR) of PET Scans With Tau Radiotracer (Where Available)
timeFrame: Baseline to Months 24 and 60
measure: Change in Amyloid Deposition as Measured by Standardized Uptake Ratio (SUVR) of Positron Emission Tomography (PET) Scan With Amyloid Radiotracer
timeFrame: Baseline to Months 24 and 60
measure: Change in CSF Levels of Total Tau and Phosphorylated Tau
timeFrame: Baseline to Last on-treatment (Day 547) Baseline to Last off-treatment (Day 648)
measure: Change in Serum Neurofilaments
timeFrame: Baseline to Week 26, baseline to Last on-treatment (Day 547) Baseline to Last off-treatment (Day 648)
measure: Number of Suicidal Ideation or Behavior Events
timeFrame: Baseline up to study termination approximately 617 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute, 901 East Willetta Street
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Building B
state: Arizona
city: Tucson
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Costa Mesa
country: United States
facility: ATP Clinical Research Inc, 3151 Airway Avenue T 3
state: California
city: Irvine
country: United States
facility: Irvine Center for Clinical Res, 2515 McCabe Way
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research Institute, 25043 Narbonne Avenue
state: California
city: Oxnard
country: United States
facility: Novartis Investigative Site
state: California
city: Palo Alto
country: United States
facility: Novartis Investigative Site
state: California
city: San Diego
country: United States
facility: Novartis Investigative Site
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research, 1401 N Tustin Ave, Suite 130
state: California
city: Sebastopol
country: United States
facility: Novartis Investigative Site
state: California
city: Sherman Oaks
country: United States
facility: Novartis Investigative Site
state: California
city: Basalt
country: United States
facility: Mountain Neurological Research, 350 Market Street, Suite 316
state: Colorado
city: Colorado Springs
country: United States
facility: Colorado Springs Neurological, 2312 North Nevada Avenue, Suite 100
state: Colorado
city: Denver
country: United States
facility: Denver Neurological Clinic, 950 E Harvard Ave
state: Colorado
city: New Haven
country: United States
facility: Yale University, One Church Street, Suite 600
state: Connecticut
city: Stamford
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: Washington
country: United States
facility: Novartis Investigative Site
state: District of Columbia
city: Atlantis
country: United States
facility: Novartis Investigative Site
state: Florida
city: Deerfield Beach
country: United States
facility: Quantum Laboratories
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research, Inc., 800 NW 17th Avenue
state: Florida
city: Hollywood
country: United States
facility: Infinity Clinical Research LLC, 4925 Sheridan Street, Suite 200
state: Florida
city: Lake Worth
country: United States
facility: Alzheimer's Research and Treatment Center, 5065 State Road 7, Suite 102
state: Florida
city: Maitland
country: United States
facility: Meridien Research, 2300 Maitland center, Pkwy Ste 230
state: Florida
city: Melbourne
country: United States
facility: Novartis Investigative Site
state: Florida
city: Merritt Island
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami Beach
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center, 11880 SW 40 St., Suite 405
state: Florida
city: Miami
country: United States
facility: Miami-Dade Medical Research, 8955 SW 87 CT, Suite 112
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC,100 West Gore Street, Suite 202
state: Florida
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
city: Ormond Beach
country: United States
facility: Novartis Investigative Site
state: Florida
city: Palm Beach Gardens
country: United States
facility: Novartis Investigative Site
state: Florida
city: Port Orange
country: United States
facility: Novartis Investigative Site
state: Florida
city: Sarasota
country: United States
facility: Roskamp Institute, Inc., 2040 Whitfield Avenue
state: Florida
city: Tallahassee
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: West Palm Beach
country: United States
facility: Novartis Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Columbus
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Decatur
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Pacific Neuroscience, 2230 Liliha st 104
state: Hawaii
city: Meridian
country: United States
facility: Advanced Clinical Research, 2950 E Magic View Dr, Suite 182
state: Idaho
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Elk Grove Village
country: United States
facility: Alexian Brothers Neuroscience, 800 Biesterfield Rd, Neuroscience Institute Brock
state: Illinois
city: Indianapolis
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Fairway
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Wichita
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Wichita
country: United States
facility: Novartis Investigative Site
state: Kansas
city: Lexington
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Bangor
country: United States
facility: Novartis Investigative Site
state: Maine
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: Farmington Hills
country: United States
facility: QUEST Research Institute, 28595 Orchard Lake Road, Suite 301
state: Michigan
city: Kalamazoo
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Rochester
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic, 415 South 28th Avenue
state: Mississippi
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Omaha
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: West Long Branch
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience, 101 Hospital Loop ne, 209 209
state: New Mexico
city: Brooklyn
country: United States
facility: Novartis Investigative Site
state: New York
city: East Syracuse
country: United States
facility: Novartis Investigative Site
state: New York
city: Latham
country: United States
facility: Novartis Investigative Site
state: New York
city: New York
country: United States
facility: NYU Langone Medical Center, 145 East 32nd Street, 2nd Floor, Room 226
state: New York
city: Orangeburg
country: United States
facility: Novartis Investigative Site
state: New York
city: Rochester
country: United States
facility: Novartis Investigative Site
state: New York
city: Charlotte
country: United States
facility: ANI Neurology, PLLC dba Alzhe, 7809 Sardis Road
state: North Carolina
city: Durham
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Greensboro
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Clinical Research LLC, 1705 E 19th ST., STE 406/408
state: Oklahoma
city: Portland
country: United States
facility: Summit Research Network, 2701 NW Vaughn St, Suite 350
state: Oregon
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Jenkintown
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Neurological Associate Ltd., 2325 Maryland Road, Suite 100
state: Pennsylvania
city: East Providence
country: United States
facility: Rhode Island Hospital and Memory Research Institute, 1018 Waterman Ave
state: Rhode Island
city: Providence
country: United States
facility: Butler Hospital, 345 Blackstone Blvd.
state: Rhode Island
city: Charleston
country: United States
facility: Roper Hospital, 316 Calhoun Street 5th Floor
state: South Carolina
city: Knoxville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Memphis
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Dallas
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Bennington
country: United States
facility: Novartis Investigative Site
state: Vermont
city: Tacoma
country: United States
facility: Novartis Investigative Site
state: Washington
city: Milwaukee
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Darlinghurst
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Heidelberg West
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Kelowna
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Kentville
country: Canada
facility: Novartis Investigative Site
state: Nova Scota
city: Halifax
country: Canada
facility: Novartis Investigative Site
state: Nova Scotia
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program, 1 Valleybrook Drive Suite 400
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Gatineau
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Greenfield Park
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Beijing
country: China
facility: Novartis Investigative Site
city: Guangdong
country: China
facility: Novartis Investigative Site
city: Kuopio
country: Finland
facility: Novartis Investigative Site
city: Turku
country: Finland
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
state: Cedex
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: PARIS Cedex 13
country: France
facility: Novartis Investigative Site
city: Rouen
country: France
facility: Novartis Investigative Site
city: Toulouse Cedex 9
country: France
facility: Novartis Investigative Site
city: Villeurbanne
country: France
facility: Novartis Investigative Site
city: Bayreuth
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Siegen
country: Germany
facility: Novartis Investigative Site
city: Kopavogi
country: Iceland
facility: Novartis Investigative Site
city: Ashkelon
country: Israel
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Roma
country: Italy
facility: Novartis Investigative Site
state: Lazio
city: Monza
country: Italy
facility: Novartis Investigative Site
state: MB
city: Milan
country: Italy
facility: Novartis Investigative Site
city: Tōon
country: Japan
facility: Novartis Investigative Site
state: Ehime
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Suita city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Kodaira
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chiba
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Suwon
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Incheon
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Ciudad de Mexico
country: Mexico
facility: Novartis Investigative Site
state: Mexico CP
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: Nuevo Leon
city: Culiacan
country: Mexico
facility: Novartis Investigative Site
state: Sinaloa
city: Den Bosch
country: Netherlands
facility: Novartis Investigative Site
state: Noord Brabant
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Torres Vedras
country: Portugal
facility: Novartis Investigative Site
state: Lisbon
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Matosinhos
country: Portugal
facility: Novartis Investigative Site
city: San Juan
country: Puerto Rico
facility: Inspira Clinical Research, Ave Hostos 405
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Rosebank
country: South Africa
facility: Novartis Investigative Site
state: Johannesburg
city: Cape Town
country: South Africa
facility: Novartis Investigative Site
state: Western Cape
city: George
country: South Africa
facility: Novartis Investigative Site
state: ZAF
city: Terrassa
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Pozuelo de Alarcon
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Donostia-San Sebastian
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
state: CH
city: Geneve
country: Switzerland
facility: Novartis Investigative Site
city: Lausanne
country: Switzerland
facility: Novartis Investigative Site
city: Kaoshiung
country: Taiwan
facility: Novartis Investigative Site
city: New Taipei City
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Exeter
country: United Kingdom
facility: Novartis Investigative Site
state: Devon
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
state: Devon
city: London
country: United Kingdom
facility: Novartis Investigative Site
state: GBR
city: Guildford
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
city: Avon
country: United Kingdom
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Bristol
country: United Kingdom
facility: Novartis Investigative Site
city: Dundee
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: