Clinical trial NCT06416072: Alzheimer's Plasma Extension
Official title: Alzheimer's Plasma Extension
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Preclinical Alzheimer's Disease
Early Preclinical Alzheimer's Disease
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: Alzheimer's Clinical Trials Consortium (ACTC)
name: Alzheimer's Therapeutic Research Institute
name: Alzheimer's Association
First posted: 2024-05-16
Enrollment: 1000
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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)


Eligibility criteria: 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).

Primary outcomes:
measure: Rate of change from Baseline to Month 48 on plasma beta-amyloid (Aβ) 40 or 42 ratio
timeFrame: Baseline, Month 12, Month 24, Month 36 and Month 48
measure: Rate of change from Baseline to Month 48 on plasma phosphorylated tau (ptau) 217
timeFrame: Baseline, Month 12, Month 24, Month 36 and Month 48
Secondary outcomes:
measure: Rate of Change from Baseline to Month 48 as measured by the Preclinical Alzheimer Cognitive Composite 5(PACC5)
timeFrame: Baseline, Month 12, Month 24, Month 36 and Month 48
measure: Rate of Change from Baseline to Month 48 as measured Cognitive Function Index (CFI)
timeFrame: Baseline, Month 12, Month 24, Month 36 and Month 48
Other outcomes:
measure: Collection of baseline amyloid PET on participants without prior amyloid PET data
timeFrame: Baseline
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Institute
state: Arizona
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: Sharp Neurocognitive Research Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Walnut Creek
country: United States
facility: University of California, Davis
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: Howard University
state: District of Columbia
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic, Jacksonville
state: Florida
city: Lady Lake
country: United States
facility: K2 Medical Research - The Villages
state: Florida
city: Maitland
country: United States
facility: K2 Medical Research, LLC
state: Florida
city: Miami Beach
country: United States
facility: Wien Center for Clinical Research
state: Florida
city: Miami
country: United States
facility: Gonzalez MD & Aswad MD Health Services
state: Florida
city: Orlando
country: United States
facility: Charter Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida - Health Byrd Alzheimer Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Fairway
country: United States
facility: University of Kansas
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Plymouth
country: United States
facility: Headlands Eastern MA LLC
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan, Ann Arbor
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic, Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University, St. Louis
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas
state: Nevada
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Beachwood
country: United States
facility: Case Western Reserve University
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Lou Ruvo Center for Brain Health, Ohio
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Tulsa
country: United States
facility: Central States Research, LLC
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Butler Hospital Memory and Aging Program
state: Rhode Island
city: Charleston
country: United States
facility: Ralph H. Johnson VA Health Care System
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center Center for Cognitive Medicine
state: Tennessee
city: Dallas
country: United States
facility: University of Texas, Southwestern MC at Dallas
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist Neurological Institute
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Norfolk
country: United States
facility: Eastern Virginia Medical School at Old Dominion University
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research Inc.
state: Virginia
city: Seattle
country: United States
facility: University of Washington, Memory and Brain Wellness Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Southern California (USC) Alzheimer's Therapeutic Research Institute (ATRI)
name: Paul Aisen, MD
role: STUDY_DIRECTOR
affiliation: Brigham and Women's Hospital and Massachusetts General Hospital
name: Reisa Sperling, MD
role: STUDY_DIRECTOR
References: