Alzheimer's Plasma Extension

NCT06416072 | Active Not Recruiting DMC

• 2 other identifiers: ATRI-0135R01AG054029
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 56

Brief Summary

The APEX study is a multicenter, observational study designed to capture longitudinal follow-up of plasma biomarkers and cognitive and functional assessments on individuals who screen failed in the AHEAD study over approximately 4 years. Approximately 1000 participants will be enrolled across three groups:

• Group A: Approximately 500 participants who are discordant on screening (plasma positive / Positron Emission Tomography (PET) negative),
• Group B: Approximately 250 participants who are concordant on screening (plasma negative / PET negative), and
• Group C: Approximately 250 participants selected from the individuals who previously screen failed prior to PET for the AHEAD study with oversampling of racial and ethnic populations underrepresented in Alzheimer's disease (AD) clinical trials. Primary Objectives:
• Collect longitudinal cognitive and functional assessments and blood-based biomarker data
• Evaluate, characterize, and compare the longitudinal cognitive and functional data between the three groups of participants
• Compare longitudinal change across race and ethnicity, sex, and Apolipoprotein E (ApoE) status Exploratory Objectives:
• Collect baseline amyloid PET on participants without prior amyloid PET data (Group C)

Conditions

Preclinical Alzheimer's Disease; Early Preclinical Alzheimer's Disease

Outcome Measures

Primary Outcomes (2)

• Rate of change from Baseline to Month 48 on plasma beta-amyloid (Aβ) 40 or 42 ratio

  Baseline, Month 12, Month 24, Month 36 and Month 48

• Rate of change from Baseline to Month 48 on plasma phosphorylated tau (ptau) 217

  Assess longitudinal changes from initial visit in plasma phosphorylated tau (ptau) 217 ratio using a proteomics assay

  Baseline, Month 12, Month 24, Month 36 and Month 48

Secondary Outcomes (2)

• Rate of Change from Baseline to Month 48 as measured by the Preclinical Alzheimer Cognitive Composite 5(PACC5)

  Baseline, Month 12, Month 24, Month 36 and Month 48

• Rate of Change from Baseline to Month 48 as measured Cognitive Function Index (CFI)

  Baseline, Month 12, Month 24, Month 36 and Month 48

Other Outcomes (1)

• Collection of baseline amyloid PET on participants without prior amyloid PET data

  Baseline

Study Arms (3)

Group A

Approximately 500 participants who screen failed from the AHEAD study that were plasma positive / PET negative

Group B

Approximately 250 participants who screen failed from the AHEAD study that were plasma negative / PET negative

Group C

Approximately 250 participants who screen failed prior to PET imaging will undergo amyloid PET imaging with NAV4694 injection.

Radiation: NAV4694

Interventions

NAV4694 RADIATION

Amyloid PET imaging with NAV4694 injection

Also known as: [18F]NAV4694

Group C

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This study will enroll approximately 1000 participants who screen failed from the AHEAD study without evidence of elevated or intermediate amyloid by plasma biomarker or by amyloid PET scan at screening. Participants will have consented to participate in the AHEAD study and previously met demographic, cognitive and clinical criteria, however, had screening plasma biomarker and/or PET scan results that fell below the ABeta threshold levels required for randomization into the treatment arms for the AHEAD study.

You may qualify if:

• Documentation of the participant's informed consent to study procedures and for the use of protected health information (HIPAA Authorization, if applicable). Informed consent processes and documentation must adhere to state laws/local requirements, including consent provided by the participant's legally authorized representative (LAR), responsible next of kin, surrogate consent with assent, etc.
• Previously consented to participate in A3-45 screening.
• Has A3-45 screening plasma biomarker results required for determining eligibility to participate in the A3-45 trial.
• If an amyloid PET scan was conducted in A3-45, the scan was determined to be below the 20 centiloid cutpoint required for eligibility into the treatment arms of the A3 or A45 trial.
• As assessed by the site PI, participant is likely to be able to comply with the protocol, including completion of all required procedures for the duration of the study, and has adequate vision, hearing (hearing aid permitted), and literacy in English or Spanish sufficient for compliance with required testing procedures.

You may not qualify if:

• Current treatment with an FDA approved medication for Alzheimer's disease, including prior or current treatment with a prohibited medication.
• Enrollment in another investigational study, or intake of investigational drug, within 30 days prior to screening, or five half-lives of the investigational drug, whichever is longer, unless it can be documented that the participant was in the placebo treatment arm.
• Participants enrolled in other observational studies may be permitted with Medical Monitor review and approval.

Sponsors & Collaborators

• University of Southern California: lead
• Alzheimer's Clinical Trials Consortium (ACTC): collaborator
• Alzheimer's Therapeutic Research Institute: collaborator
• Alzheimer's Association: collaborator

Study Sites (56)

University of Alabama, Birmingham

Birmingham, Alabama, 35233, United States

Location

Banner Alzheimer's Institute

Phoenix, Arizona, 85006, United States

Location

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

University of California, Irvine

Irvine, California, 92697, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Sharp Neurocognitive Research Center

San Diego, California, 92123, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

University of California, Davis

Walnut Creek, California, 94598, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Howard University

Washington D.C., District of Columbia, 20060, United States

Location

Brain Matters Research

Delray Beach, Florida, 33445, United States

Location

Mayo Clinic, Jacksonville

Jacksonville, Florida, 32224, United States

Location

K2 Medical Research - The Villages

Lady Lake, Florida, 32159, United States

Location

K2 Medical Research, LLC

Maitland, Florida, 32751, United States

Location

Gonzalez MD & Aswad MD Health Services

Miami, Florida, 33135, United States

Location

Wien Center for Clinical Research

Miami Beach, Florida, 33140, United States

Location

Charter Research

Orlando, Florida, 32803, United States

Location

University of South Florida - Health Byrd Alzheimer Institute

Tampa, Florida, 33613, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Kansas

Fairway, Kansas, 66205, United States

Location

University of Kentucky

Lexington, Kentucky, 40504, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21224, United States

Location

Boston University

Boston, Massachusetts, 02215, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 21155, United States

Location

Headlands Eastern MA LLC

Plymouth, Massachusetts, 02360, United States

Location

University of Michigan, Ann Arbor

Ann Arbor, Michigan, 48105, United States

Location

Mayo Clinic, Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University, St. Louis

St Louis, Missouri, 63108, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas

Las Vegas, Nevada, 89101, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14620, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Case Western Reserve University

Beachwood, Ohio, 44122, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain Health, Ohio

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Central States Research, LLC

Tulsa, Oklahoma, 74136, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Butler Hospital Memory and Aging Program

Providence, Rhode Island, 02906, United States

Location

Ralph H. Johnson VA Health Care System

Charleston, South Carolina, 29401, United States

Location

Vanderbilt University Medical Center Center for Cognitive Medicine

Nashville, Tennessee, 37212, United States

Location

University of Texas, Southwestern MC at Dallas

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Houston Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Eastern Virginia Medical School at Old Dominion University

Norfolk, Virginia, 23510, United States

Location

National Clinical Research Inc.

Richmond, Virginia, 23294, United States

Location

University of Washington, Memory and Brain Wellness Center

Seattle, Washington, 98195, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Links

• Alzheimer's Clinical Trials Consortium
• Alzheimer's Therapeutic Research Institute
• APEX Study Home Page

Biospecimen

Retention: SAMPLES WITH DNA

blood, plasma

Study Officials

• Paul Aisen, MD

  University of Southern California (USC) Alzheimer's Therapeutic Research Institute (ATRI)

  STUDY DIRECTOR

• Reisa Sperling, MD

  Brigham and Women's Hospital and Massachusetts General Hospital

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 21, 2023
• First Posted: May 16, 2024
• Study Start: September 21, 2023
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: June 10, 2025

Record last verified: 2025-06

Locations

US (56)