Alzheimer's Plasma Extension

Preclinical Alzheimer's Disease Clinical Trial

— APEX  

Official title:

Alzheimer's Plasma Extension

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06416072
• Other study ID #: ATRI-013
• Secondary ID: 5R01AG054029
• Status: Enrolling by invitation
• Start date: September 21, 2023
• Est. completion date: June 2028

Study information

• Verified date: May 2024
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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)

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 1000
• Est. completion date: June 2028
• Est. primary completion date: June 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 55 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Alzheimer Disease
• Early Preclinical Alzheimer's Disease
• Preclinical Alzheimer's Disease

Intervention

Radiation:
• NAV4694
Amyloid PET imaging with NAV4694 injection

Locations

Country	Name	City	State
United States	University of Michigan, Ann Arbor	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Case Western Reserve University	Beachwood	Ohio
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	Boston University	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Ralph H. Johnson VA Health Care System	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	University of Texas, Southwestern MC at Dallas	Dallas	Texas
United States	Brain Matters Research	Delray Beach	Florida
United States	University of Kansas	Fairway	Kansas
United States	Baylor College of Medicine	Houston	Texas
United States	Houston Methodist Neurological Institute	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	University of California, Irvine	Irvine	California
United States	Mayo Clinic, Jacksonville	Jacksonville	Florida
United States	Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas	Las Vegas	Nevada
United States	University of Kentucky	Lexington	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	K2 Medical Research, LLC	Maitland	Florida
United States	Gonzalez MD & Aswad MD Health Services	Miami	Florida
United States	Wien Center for Clinical Research	Miami Beach	Florida
United States	Vanderbilt University Medical Center Center for Cognitive Medicine	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	Stanford University	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	Headlands Eastern MA LLC	Plymouth	Massachusetts
United States	Butler Hospital Memory and Aging Program	Providence	Rhode Island
United States	National Clinical Research Inc.	Richmond	Virginia
United States	Mayo Clinic, Rochester	Rochester	Minnesota
United States	University of Rochester Medical Center	Rochester	New York
United States	Washington University, St. Louis	Saint Louis	Missouri
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Sharp Neurocognitive Research Center	San Diego	California
United States	University of Washington, Memory and Brain Wellness Center	Seattle	Washington
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	University of South Florida - Health Byrd Alzheimer Institute	Tampa	Florida
United States	Central States Research	Tulsa	Oklahoma
United States	University of California, Davis	Walnut Creek	California
United States	Georgetown University	Washington	District of Columbia
United States	Howard University	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	Charter Research	Winter Park	Florida

Sponsors (4)

Lead Sponsor	Collaborator
University of Southern California	Alzheimer's Clinical Trials Consortium (ACTC), Alzheimer's Therapeutic Research Institute, National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Collection of baseline amyloid PET on participants without prior amyloid PET data		Baseline
Primary	Rate of change from Baseline to Month 48 on plasma beta-amyloid (Aß) 40 or 42 ratio		Baseline, Month 12, Month 24, Month 36 and Month 48
Primary	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	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
Secondary	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

External Links

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