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

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.

Sponsors

Lead Sponsor: Novartis Pharmaceuticals

Collaborator: Banner Alzheimer's Institute
National Institute on Aging (NIA)
Alzheimer's Association
Amgen

Source Novartis
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.

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.

Overall Status Terminated
Start Date November 30, 2015
Completion Date April 30, 2020
Primary Completion Date April 30, 2020
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Time to diagnosis of MCI due to Alzheimer's Disease (AD) or dementia due to Alzheimer's Disease Through study completion, an average of 5 years
Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score Baseline to Month 60
Secondary Outcome
Measure Time Frame
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score Baseline to Month 60
Number of participants with Adverse Events as a measure of Safety and Tolerability Through study completion, an average of 5 years
Change on the Total Scale score and individual neurocognitive domain index scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Baseline to Month 60
Change in the Everyday Cognition scale (ECog) total scores Baseline to Month 60
Change in Alzheimer's Disease related biomarkers Baseline to Months 24 and 60
Change in APCC Test Score Month 6 to Month 60
Change in CDR-SOB Month 6 to Month 60
Aβ-specific immune response Through study completion, an average of 5 years
Enrollment 480
Condition
Intervention

Intervention Type: Biological

Intervention Name: CAD106 Immunotherapy

Description: 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.

Arm Group Label: Arm#1

Intervention Type: Other

Intervention Name: Placebo to CAD106

Description: 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.

Arm Group Label: Arm#2

Intervention Type: Drug

Intervention Name: CNP520

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

Arm Group Label: Arm#3

Intervention Type: Other

Intervention Name: Placebo to CNP520

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

Arm Group Label: Arm#4

Eligibility

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.

Gender: All

Minimum Age: 60 Years

Maximum Age: 75 Years

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals
Location
Facility:
Banner Alzheimer's Institute | Phoenix, Arizona, 85006, United States
Novartis Investigative Site | Phoenix, Arizona, 85006, United States
Novartis Investigative Site | Scottsdale, Arizona, 85259, United States
Banner Sun City Research Institute | Sun City, Arizona, 85351, United States
ATP Clinical Research, Inc. | Costa Mesa, California, 92626, United States
Irvine Center for Clinical Research | Irvine, California, 92614, United States
University of Southern California Keck School of Medicine Alzheimer Disease Research Center | Los Angeles, California, 90033, United States
Novartis Investigative Site | Palo Alto, California, 94304, United States
Novartis Investigative Site | San Diego, California, 92103, United States
Syrentis Clinical Research | Santa Ana, California, 92705, United States
Novartis Investigative Site | Sebastopol, California, 95472, United States
California Neuroscience Research Medical Group, Inc. | Sherman Oaks, California, 91316, United States
Novartis Investigative Site | Basalt, Colorado, 81621, United States
Yale University Alzheimer's Disease Research Unit | New Haven, Connecticut, 06510, United States
New England Institute for Clinical Research | Stamford, Connecticut, 06905, United States
Georgetown University | Washington, District of Columbia, 20057, United States
JEM Research Institute | Atlantis, Florida, 33462-6608, United States
Florida Atlantic University, Clinical Translational Research Unit | Boca Raton, Florida, 33431, United States
Brain Matters Research | Delray Beach, Florida, 33445, United States
Meridien Research | Maitland, Florida, 32751, United States
Merritt Island Medical Research | Merritt Island, Florida, 32952, United States
Mount Sinai Medical Center - The Wien Center | Miami Beach, Florida, 33140, United States
University of Miami | Miami, Florida, 33136, United States
Novartis Investigative Site | Orlando, Florida, 32806, United States
Compass Research | Orlando, Florida, 32812, United States
Progressive Medical Research | Port Orange, Florida, 32127, United States
USF Health Byrd Alzheimer's Institute | Tampa, Florida, 33613, United States
Novartis Investigative Site | Atlanta, Georgia, 30322, United States
Medical Research & Health Education Foundation, Inc. | Columbus, Georgia, 31909, United States
NeuroStudies | Decatur, Georgia, 30033, United States
Advanced Clinical Research | Meridian, Idaho, 83642, United States
Rush University Medical Center | Chicago, Illinois, 60612, United States
Great Lakes Clinical Trials | Chicago, Illinois, 60640, United States
Indiana University | Indianapolis, Indiana, 46202, United States
University of Kansas Alzheimer's Disease Center | Fairway, Kansas, 66205, United States
Via Christi Research | Wichita, Kansas, 67214, United States
Sanders Brown Center on Aging, University of Kentucky | Lexington, Kentucky, 40504, United States
Novartis Investigative Site | Boston, Massachusetts, 02115, United States
Novartis Investigative Site | Rochester, Minnesota, 55905, United States
Memory Disorders Program, Department of Neurological Sciences, University of Nebraska Medical Center | Omaha, Nebraska, 68198-7680, United States
Cleveland Clinic Lou Ruvo Center for Brain Health | Las Vegas, Nevada, 89106, United States
Memory Enhancement Center | Eatontown, New Jersey, 07724, United States
The Memory Center of Northeastern New York | Latham, New York, 12110, United States
NYU Langone Medical Center | New York, New York, 10016, United States
The Nathan S. Kline Institute | Orangeburg, New York, 10962, United States
University of Rochester Medical Center | Rochester, New York, 14620, United States
Alzheimer's Memory Center | Charlotte, North Carolina, 28270, United States
Duke University Medical center | Durham, North Carolina, 27705, United States
Triad Clinical Trials, LLC | Greensboro, North Carolina, 27410, United States
University Hospitals Cleveland Medical Center / Case Western Reserve University | Beachwood, Ohio, 44122, United States
Novartis Investigative Site | Columbus, Ohio, 43210, United States
IPS Research Company | Oklahoma City, Oklahoma, 73103, United States
Memory Health Center at Summit Research Network | Portland, Oregon, 97210, United States
The Clinical Trial Center, LLC | Jenkintown, Pennsylvania, 19046, United States
Novartis Investigative Site | Philadelphia, Pennsylvania, 19104, United States
Abington Neurological Associates | Willow Grove, Pennsylvania, 19090, United States
Butler Hospital Memory and Aging Program | Providence, Rhode Island, 02906, United States
Roper St. Francis - CBRI | Charleston, South Carolina, 29401, United States
Novartis Investigative Site | Knoxville, Tennessee, 37920, United States
CNS Healthcare | Memphis, Tennessee, 38119, United States
Novartis Investigative Site | Nashville, Tennessee, 37212, United States
Senior Adults Specialty Research | Austin, Texas, 78757, United States
Kerwin Research Center & Memory Care | Dallas, Texas, 75231, United States
Houston Methodist Hospital | Houston, Texas, 77030, United States
University of Texas Health Science Center, Houston | Houston, Texas, 77054, United States
Clinical Trial Network | Houston, Texas, 77074, United States
The Memory Clinic | Bennington, Vermont, 05201, United States
Universal Research Group | Tacoma, Washington, 98405, United States
The Medical College of WI | Milwaukee, Wisconsin, 53226, United States
Novartis Investigative Site | Darlinghurst, New South Wales, 2010, Australia
Novartis Investigative Site | Leuven, 3000, Belgium
Okanagan Clinical Trials | Kelowna, British Columbia, V1Y1Z9, Canada
Novartis Investigative Site | Kentville, Nova Scota, B4N 4K9, Canada
Novartis Investigative Site | Halifax, Nova Scotia, B3S 1M7, Canada
Toronto Memory Program | Toronto, Ontario, M3B 2S7, Canada
The Centre for Memory and Aging | Toronto, Ontario, M4G 3E8, Canada
Novartis Investigative Site | Gatineau, Quebec, J8T 8J1, Canada
Novartis Investigative Site | Sherbrooke, Quebec, J1J 2G2, Canada
Novartis Investigative Site | Turku, 20520, Finland
Novartis Investigative Site | Bayreuth, 95445, Germany
Novartis Investigative Site | Berlin, 13353, Germany
Novartis Investigative Site | Mannheim, 68159, Germany
Novartis Investigative Site | Münster, 48149, Germany
Novartis Investigative Site | Amsterdam, 1081 GN, Netherlands
Novartis Investigative Site | Barcelona, 08005, Spain
Novartis Investigative Site | Donostia-San Sebastian, 20009, Spain
Novartis Investigative Site | Basel, CH, 4002, Switzerland
Novartis Investigative Site | Lausanne, CH-1011, Switzerland
Novartis Investigative Site | Westbruy On Trym, Bristol, BS10 5NB, United Kingdom
Novartis Investigative Site | Plymouth, Devon, PL6 8BT, United Kingdom
Novartis Investigative Site | Guildford, Surrey, GU27YD, United Kingdom
Novartis Investigative Site | Avon, BA1 3NG, United Kingdom
Novartis Investigative Site | Birmingham, B16 8QQ, United Kingdom
Novartis Investigative Site | Dundee, DD1 9SY, United Kingdom
Novartis Investigative Site | Glasgow, G20 0XA, United Kingdom
Novartis Investigative Site | Glasgow, United Kingdom
Novartis Investigative Site | London, W12 0HS, United Kingdom
Novartis Investigative Site | London, W1G 9JF, United Kingdom
Novartis Investigative Site | London, W2 1PG, United Kingdom
Location Countries

Australia

Belgium

Canada

Finland

Germany

Netherlands

Spain

Switzerland

United Kingdom

United States

Verification Date

July 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Arm#1

Type: Experimental

Description: CAD106 (450 µg) + Alum (450 µg) given i.m. at week 1, 7, 13 and quarterly thereafter

Label: Arm#2

Type: Placebo Comparator

Description: Placebo to CAD106 + Alum (450 µg) given i.m. at week 1, 7, 13 and quarterly thereafter

Label: Arm#3

Type: Experimental

Description: CNP520 (50 mg) capsules oral intake (p.o.)

Label: Arm#4

Type: Placebo Comparator

Description: Placebo to CNP520 capsules oral intake (p.o.)

Acronym Generation S1
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov