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

NCT02565511 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: CAPI015A2201J2015-002715-151UF1AG046150-01
• Study Type: interventional
• Target: 480
• Locations: 10 countries
• Sites: 129

Brief Summary

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.

Conditions

Alzheimers Disease

Keywords

Randomization; Placebo controlled; Parallel-group; APOE4 Homozygotes; Preclinical Alzheimers Disease (AD); Aβ lowering; CNP520; CAD106; elderly; Brain Amyloid; BACE-1 inhibitor; Prevention; Unimpaired cognition

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (17)

• Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score

  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).

  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).

  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

  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

  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

Study Arms (4)

Cohort I (CAD106)

EXPERIMENTAL

CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter

Biological: CAD106 Immunotherapy; Other: Alum

Cohort I (CAD106 Placebo)

PLACEBO COMPARATOR

Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter

Other: Placebo to CAD106; Other: Alum

Cohort II (CNP520)

EXPERIMENTAL

CNP520 (50 mg) capsules taken orally once daily

Drug: CNP520

Cohort II (CNP520 Placebo)

PLACEBO COMPARATOR

Matching Placebo to CNP520 capsules taken orally once daily

Other: Placebo to CNP520

Interventions

CAD106 Immunotherapy BIOLOGICAL

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.

Cohort I (CAD106)

Placebo to CAD106 OTHER

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.

Cohort I (CAD106 Placebo)

CNP520 DRUG

CNP520 50 mg capsule p.o. for the duration of the Treatment Epoch.

Cohort II (CNP520)

Placebo to CNP520 OTHER

Placebo to CNP520 p.o. for the duration of the Treatment Epoch

Cohort II (CNP520 Placebo)

Alum OTHER

Alum was mixed with reconstituted CAD106 as adjuvant therapy to maximize the effectiveness of CAD106

Cohort I (CAD106 Placebo); Cohort I (CAD106)

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Banner Alzheimer's Institute: collaborator
• National Institute on Aging (NIA): collaborator
• Amgen: collaborator

Study Sites (129)

Banner Alzheimer's Institute

Phoenix, Arizona, 85006, United States

Location

Novartis Investigative Site

Phoenix, Arizona, 85006, United States

Location

Novartis Investigative Site

Scottsdale, Arizona, 85259, United States

Location

Banner Sun City Research Institute

Sun City, Arizona, 85351, United States

Location

ATP Clinical Research, Inc.

Costa Mesa, California, 92626, United States

Location

Irvine Center for Clinical Research

Irvine, California, 92614, United States

Location

University of Southern California Keck School of Medicine Alzheimer Disease Research Center

Los Angeles, California, 90033, United States

Location

Novartis Investigative Site

Palo Alto, California, 94304, United States

Location

Novartis Investigative Site

San Diego, California, 92103, United States

Location

Syrentis Clinical Research

Santa Ana, California, 92705, United States

Location

Novartis Investigative Site

Sebastopol, California, 95472, United States

Location

California Neuroscience Research Medical Group, Inc.

Sherman Oaks, California, 91316, United States

Location

Novartis Investigative Site

Temecula, California, 92591, United States

Location

Novartis Investigative Site

Basalt, Colorado, 81621, United States

Location

Yale University Alzheimer's Disease Research Unit

New Haven, Connecticut, 06510, United States

Location

New England Institute for Clinical Research

Stamford, Connecticut, 06905, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

Novartis Investigative Site

Washington D.C., District of Columbia, 20059, United States

Location

JEM Research Institute

Atlantis, Florida, 33462-6608, United States

Location

Florida Atlantic University, Clinical Translational Research Unit

Boca Raton, Florida, 33431, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Novartis Investigative Site

Jacksonville, Florida, 32224, United States

Location

Meridien Research

Maitland, Florida, 32751, United States

Location

Merritt Island Medical Research

Merritt Island, Florida, 32952, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Mount Sinai Medical Center - The Wien Center

Miami Beach, Florida, 33140, United States

Location

Novartis Investigative Site

Orlando, Florida, 32806, United States

Location

Compass Research

Orlando, Florida, 32812, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

USF Health Byrd Alzheimer's Institute

Tampa, Florida, 33613, United States

Location

Novartis Investigative Site

Atlanta, Georgia, 30322, United States

Location

Medical Research & Health Education Foundation, Inc.

Columbus, Georgia, 31909, United States

Location

NeuroStudies

Decatur, Georgia, 30033, United States

Location

Advanced Clinical Research

Meridian, Idaho, 83642, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Great Lakes Clinical Trials

Chicago, Illinois, 60640, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Alzheimer's Disease Center

Fairway, Kansas, 66205, United States

Location

Via Christi Research

Wichita, Kansas, 67214, United States

Location

Sanders Brown Center on Aging, University of Kentucky

Lexington, Kentucky, 40504, United States

Location

Novartis Investigative Site

Bangor, Maine, 04401, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02115, United States

Location

Novartis Investigative Site

Boston, Massachusetts, 02118, United States

Location

Novartis Investigative Site

Kalamazoo, Michigan, 49008, United States

Location

Novartis Investigative Site

Saint Paul, Minnesota, 55130, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63104, United States

Location

Memory Disorders Program, Department of Neurological Sciences, University of Nebraska Medical Center

Omaha, Nebraska, 68198-7680, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, 89106, United States

Location

Memory Enhancement Center

Eatontown, New Jersey, 07724, United States

Location

The Memory Center of Northeastern New York

Latham, New York, 12110, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

The Nathan S. Kline Institute

Orangeburg, New York, 10962, United States

Location

University of Rochester Medical Center

Rochester, New York, 14620, United States

Location

Alzheimer's Memory Center

Charlotte, North Carolina, 28270, United States

Location

Duke University Medical center

Durham, North Carolina, 27705, United States

Location

Triad Clinical Trials, LLC

Greensboro, North Carolina, 27410, United States

Location

University Hospitals Cleveland Medical Center / Case Western Reserve University

Beachwood, Ohio, 44122, United States

Location

Novartis Investigative Site

Centerville, Ohio, 45459, United States

Location

Novartis Investigative Site

Columbus, Ohio, 43210, United States

Location

IPS Research Company

Oklahoma City, Oklahoma, 73103, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73112, United States

Location

Memory Health Center at Summit Research Network

Portland, Oregon, 97210, United States

Location

The Clinical Trial Center, LLC

Jenkintown, Pennsylvania, 19046, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19104, United States

Location

Abington Neurological Associates

Willow Grove, Pennsylvania, 19090, United States

Location

Butler Hospital Memory and Aging Program

Providence, Rhode Island, 02906, United States

Location

Roper St. Francis - CBRI

Charleston, South Carolina, 29401, United States

Location

Novartis Investigative Site

Knoxville, Tennessee, 37920, United States

Location

CNS Healthcare

Memphis, Tennessee, 38119, United States

Location

Novartis Investigative Site

Nashville, Tennessee, 37212, United States

Location

Senior Adults Specialty Research

Austin, Texas, 78757, United States

Location

Kerwin Research Center & Memory Care

Dallas, Texas, 75231, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center, Houston

Houston, Texas, 77054, United States

Location

Clinical Trial Network

Houston, Texas, 77074, United States

Location

The Memory Clinic

Bennington, Vermont, 05201, United States

Location

Universal Research Group

Tacoma, Washington, 98405, United States

Location

The Medical College of WI

Milwaukee, Wisconsin, 53226, United States

Location

Novartis Investigative Site

Darlinghurst, New South Wales, 2010, Australia

Location

Novartis Investigative Site

Heidelberg Heights, Victoria, 3081, Australia

Location

Novartis Investigative Site

Nedlands, Western Australia, 6009, Australia

Location

Novartis Investigative Site

Ghent, 9000, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Okanagan Clinical Trials

Kelowna, British Columbia, V1Y1Z9, Canada

Location

Novartis Investigative Site

Kentville, Nova Scota, B4N 4K9, Canada

Location

Novartis Investigative Site

Halifax, Nova Scotia, B3S 1M7, Canada

Location

Novartis Investigative Site

London, Ontario, N6C 0A7, Canada

Location

Toronto Memory Program

Toronto, Ontario, M3B 2S7, Canada

Location

The Centre for Memory and Aging

Toronto, Ontario, M4G 3E8, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M4N 3M5, Canada

Location

Novartis Investigative Site

Gatineau, Quebec, J8T 8J1, Canada

Location

Novartis Investigative Site

Québec, Quebec, G1J 1Z4, Canada

Location

Novartis Investigative Site

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Novartis Investigative Site

Sherbrooke, Quebec, J1J 2G2, Canada

Location

Novartis Investigative Site

Turku, 20520, Finland

Location

Novartis Investigative Site

Bayreuth, 95445, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Böblingen, 71032, Germany

Location

Novartis Investigative Site

Cologne, 50937, Germany

Location

Novartis Investigative Site

Göttingen, 37075, Germany

Location

Novartis Investigative Site

Halle, 06120, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Leipzig, 04107, Germany

Location

Novartis Investigative Site

Mannheim, 68159, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Siegen, 57076, Germany

Location

Novartis Investigative Site

Wenzenbach, 93173, Germany

Location

Novartis Investigative Site

Amsterdam, 1081 GN, Netherlands

Location

Novartis Investigative Site

Terrassa, Barcelona, 08221, Spain

Location

Novartis Investigative Site

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Novartis Investigative Site

Barcelona, 08005, Spain

Location

Novartis Investigative Site

Barcelona, 08014, Spain

Location

Novartis Investigative Site

Donostia / San Sebastian, 20009, Spain

Location

Novartis Investigative Site

Basel, CH, 4002, Switzerland

Location

Novartis Investigative Site

Westbruy on Trym, Bristol, BS10 5NB, United Kingdom

Location

Novartis Investigative Site

Exeter, Devon, EX2 5DW, United Kingdom

Location

Novartis Investigative Site

Plymouth, Devon, PL6 8BT, United Kingdom

Location

Novartis Investigative Site

Guildford, Surrey, GU27YD, United Kingdom

Location

Novartis Investigative Site

Avon, BA1 3NG, United Kingdom

Location

Novartis Investigative Site

Birmingham, B16 8QQ, United Kingdom

Location

Novartis Investigative Site

Dundee, DD1 9SY, United Kingdom

Location

Novartis Investigative Site

Glasgow, G20 0XA, United Kingdom

Location

Novartis Investigative Site

Glasgow, United Kingdom

Location

Novartis Investigative Site

London, SE5 8AD, United Kingdom

Location

Novartis Investigative Site

London, W12 0HS, United Kingdom

Location

Novartis Investigative Site

London, W1G 9JF, United Kingdom

Location

Novartis Investigative Site

London, W2 1NY, United Kingdom

Location

Novartis Investigative Site

London, W2 1PG, United Kingdom

Location

Novartis Investigative Site

Manchester, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Umibecestat; aluminum sulfate

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2015
• First Posted: October 1, 2015
• Study Start: November 30, 2015
• Primary Completion: April 30, 2020
• Study Completion: April 30, 2020
• Last Updated: July 8, 2021
• Results First Posted: July 8, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will share

Locations

GB (15); US (78); CA (11); AU (3); NL (1); DE (12); FI (1); CH (1); BE (2); ES (5)