Alzheimer's Plasma Extension (APEX)

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Preclinical Alzheimer's Disease; Early Preclinical Alzheimer's Disease
• Intervention / Treatment: Radiation: NAV4694

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama, Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Institute
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Diego, California, United States, 92123
      • Sharp Neurocognitive Research Center
    • San Francisco, California, United States, 94158
      • University of California, San Francisco
    • Walnut Creek, California, United States, 94598
      • University of California, Davis
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • Howard University
    • Washington, District of Columbia, United States, 20007
      • Georgetown University
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic, Jacksonville
    • Lady Lake, Florida, United States, 32159
      • K2 Medical Research - The Villages
    • Maitland, Florida, United States, 32751
      • K2 Medical Research, LLC
    • Miami, Florida, United States, 33135
      • Gonzalez MD & Aswad MD Health Services
    • Miami Beach, Florida, United States, 33140
      • Wien Center for Clinical Research
    • Orlando, Florida, United States, 32803
      • Charter Research
    • Tampa, Florida, United States, 33613
      • University of South Florida - Health Byrd Alzheimer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • University of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Boston University
    • Boston, Massachusetts, United States, 21155
      • Brigham and Women's Hospital
    • Plymouth, Massachusetts, United States, 02360
      • Headlands Eastern MA LLC
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan, Ann Arbor
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic, Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Washington University, St. Louis
  • Nevada
    • Las Vegas, Nevada, United States, 89101
      • Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • Rochester, New York, United States, 14620
      • University of Rochester Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Lou Ruvo Center for Brain Health, Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Central States Research, LLC
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Butler Hospital Memory and Aging Program
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Ralph H. Johnson VA Health Care System
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center Center for Cognitive Medicine
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas, Southwestern MC at Dallas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • Houston Methodist Neurological Institute
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Eastern Virginia Medical School at Old Dominion University
    • Richmond, Virginia, United States, 23294
      • National Clinical Research Inc.
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington, Memory and Brain Wellness Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• 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.

Description

Inclusion Criteria:

1. 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.
2. Previously consented to participate in A3-45 screening.
3. Has A3-45 screening plasma biomarker results required for determining eligibility to participate in the A3-45 trial.
4. 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.
5. 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.

Exclusion Criteria:

1. Current treatment with an FDA approved medication for Alzheimer's disease, including prior or current treatment with a prohibited medication.

2. 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.

3. Screen failed from A3-45 due to not meeting basic inclusion criterion (i.e., age requirement; current diagnosis of AD dementia).

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; Amyloid PET imaging with NAV4694 injection; Other Names: [18F]NAV4694

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Change from Baseline to Month 48 as measured by the Preclinical Alzheimer Cognitive Composite 5(PACC5)	PACC5:Free/cued selective reminding test:number of words recalled without cuing/with cuing(0[worst]-96[best recall]);Delayed Paragraph Recall test: recall of 1 short story(25 bits information),immediately after reading and again after delay of 30 minutes (0[worst]-25[best recall]);Digit-symbol substitution test: Participant uses a key to fill in blank squares as fast as possible in 90 seconds(0[none]-91[best performance]);Mini Mental State Score:to evaluate orientation, memory, attention, concentration, naming, repetition, comprehension and ability to create sentence, to copy 2 overlapping pentagons, scored as number of correctly completed items(0[worse]-30[perfect performance]);Category fluency task: participants generate words in 60 second belonging to a semantic category(total score:number of appropriate words generated per task, higher values indicate better performance).	Baseline, Month 12, Month 24, Month 36 and Month 48
Rate of Change from Baseline to Month 48 as measured Cognitive Function Index (CFI)	CFI assessment to assess the participant's perceived ability to perform high-level functional tasks in daily life and sense of overall cognitive functional ability. Study participants (18 questions) and their study partners (15 questions) independently rate the participant's abilities. Total score combines participant and study partner scores, with higher scores indicating greater impairment. For participants, 0 = minimum;18 = maximum. For study partners, 0 = minimum; 15 = maximum. The CFI may be self-administered or completed as an interview conducted by clinical site personnel in-person or, if necessary, over the phone.	Baseline, Month 12, Month 24, Month 36 and Month 48

Other Outcome Measures

Outcome Measure	Time Frame
Collection of baseline amyloid PET on participants without prior amyloid PET data	Baseline

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: Alzheimer's Therapeutic Research Institute; Alzheimer's Association; Alzheimer's Clinical Trials Consortium (ACTC)
• Investigators: Study Director: 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

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2023
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: February 21, 2023
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 16, 2024

Study Record Updates

• Last Update Posted (Actual): June 10, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: ATRI-013; 5R01AG054029 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No