## Protocol Section
### Identification Module
**NCT ID:** NCT06416072

**Acronym:** APEX

**Brief Title:** Alzheimer's Plasma Extension

**Official Title:** Alzheimer's Plasma Extension

#### Organization Study ID Info
**ID:** ATRI-013
#### Organization
**Class:** OTHER
**Full Name:** University of Southern California
#### Secondary ID Infos
**ID:** 5R01AG054029
**Link:** https://reporter.nih.gov/quickSearch/5R01AG054029
**Type:** NIH
### Status Module
#### Completion Date
**Date:** 2028-06

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-28

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-24

**Overall Status:** ENROLLING_BY_INVITATION

#### Primary Completion Date
**Date:** 2028-06

**Type:** ESTIMATED

#### Start Date
**Date:** 2023-09-21

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2023-02-21
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Collaborators

**Class:** NIH

**Name:** National Institute on Aging (NIA)

**Class:** UNKNOWN

**Name:** Alzheimer's Clinical Trials Consortium (ACTC)

**Class:** OTHER

**Name:** Alzheimer's Therapeutic Research Institute

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Southern California

#### Responsible Party

**Investigator Affiliation:** University of Southern California

**Investigator Full Name:** Paul S. Aisen

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**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 Module

**Conditions:**

- Preclinical Alzheimer's Disease

- Early Preclinical Alzheimer's Disease

### Design Module

#### Bio Spec

**Description:** blood, plasma

**Retention:** SAMPLES_WITH_DNA

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 1000

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

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

**Label:** Group A

#### Arm Group 2

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

**Label:** Group B

#### Arm Group 3

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

**Intervention Names:**

- Radiation: NAV4694

**Label:** Group C

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Group C

**Description:** Amyloid PET imaging with NAV4694 injection

**Name:** NAV4694

**Other Names:**

- [18F]NAV4694

**Type:** RADIATION

### Outcomes Module

#### Other Outcomes

**Measure:** Collection of baseline amyloid PET on participants without prior amyloid PET data

**Time Frame:** Baseline

#### Primary Outcomes

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

**Time Frame:** Baseline, Month 12, Month 24, Month 36 and Month 48

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

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

**Time Frame:** Baseline, Month 12, Month 24, Month 36 and Month 48

#### Secondary Outcomes

**Description:** 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).

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

**Time Frame:** Baseline, Month 12, Month 24, Month 36 and Month 48

**Description:** 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.

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

**Time Frame:** Baseline, Month 12, Month 24, Month 36 and Month 48

### Eligibility Module

**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).

**Healthy Volunteers:** True

**Maximum Age:** 80 Years

**Minimum Age:** 55 Years

**Sampling Method:** PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**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.

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Birmingham

**Country:** United States

**Facility:** University of Alabama, Birmingham

**State:** Alabama

**Zip:** 35233

**Location 2:**

**City:** Phoenix

**Country:** United States

**Facility:** Banner Alzheimer's Institute

**State:** Arizona

**Zip:** 85006

**Location 3:**

**City:** Sun City

**Country:** United States

**Facility:** Banner Sun Health Research Institute

**State:** Arizona

**Zip:** 85351

**Location 4:**

**City:** Irvine

**Country:** United States

**Facility:** University of California, Irvine

**State:** California

**Zip:** 92697

**Location 5:**

**City:** Palo Alto

**Country:** United States

**Facility:** Stanford University

**State:** California

**Zip:** 94304

**Location 6:**

**City:** San Diego

**Country:** United States

**Facility:** Sharp Neurocognitive Research Center

**State:** California

**Zip:** 92123

**Location 7:**

**City:** Walnut Creek

**Country:** United States

**Facility:** University of California, Davis

**State:** California

**Zip:** 94598

**Location 8:**

**City:** New Haven

**Country:** United States

**Facility:** Yale University School of Medicine

**State:** Connecticut

**Zip:** 06510

**Location 9:**

**City:** Washington

**Country:** United States

**Facility:** Georgetown University

**State:** District of Columbia

**Zip:** 20007

**Location 10:**

**City:** Washington

**Country:** United States

**Facility:** Howard University

**State:** District of Columbia

**Zip:** 20060

**Location 11:**

**City:** Delray Beach

**Country:** United States

**Facility:** Brain Matters Research

**State:** Florida

**Zip:** 33445

**Location 12:**

**City:** Jacksonville

**Country:** United States

**Facility:** Mayo Clinic, Jacksonville

**State:** Florida

**Zip:** 32224

**Location 13:**

**City:** Maitland

**Country:** United States

**Facility:** K2 Medical Research, LLC

**State:** Florida

**Zip:** 32751

**Location 14:**

**City:** Miami Beach

**Country:** United States

**Facility:** Wien Center for Clinical Research

**State:** Florida

**Zip:** 33140

**Location 15:**

**City:** Miami

**Country:** United States

**Facility:** Gonzalez MD & Aswad MD Health Services

**State:** Florida

**Zip:** 33135

**Location 16:**

**City:** Tampa

**Country:** United States

**Facility:** University of South Florida - Health Byrd Alzheimer Institute

**State:** Florida

**Zip:** 33613

**Location 17:**

**City:** Winter Park

**Country:** United States

**Facility:** Charter Research

**State:** Florida

**Zip:** 32792

**Location 18:**

**City:** Atlanta

**Country:** United States

**Facility:** Emory University

**State:** Georgia

**Zip:** 30322

**Location 19:**

**City:** Chicago

**Country:** United States

**Facility:** Northwestern University

**State:** Illinois

**Zip:** 60611

**Location 20:**

**City:** Chicago

**Country:** United States

**Facility:** Rush University Medical Center

**State:** Illinois

**Zip:** 60612

**Location 21:**

**City:** Indianapolis

**Country:** United States

**Facility:** Indiana University

**State:** Indiana

**Zip:** 46202

**Location 22:**

**City:** Fairway

**Country:** United States

**Facility:** University of Kansas

**State:** Kansas

**Zip:** 66205

**Location 23:**

**City:** Lexington

**Country:** United States

**Facility:** University of Kentucky

**State:** Kentucky

**Zip:** 40504

**Location 24:**

**City:** Boston

**Country:** United States

**Facility:** Boston University

**State:** Massachusetts

**Zip:** 02215

**Location 25:**

**City:** Boston

**Country:** United States

**Facility:** Brigham and Women's Hospital

**State:** Massachusetts

**Zip:** 21155

**Location 26:**

**City:** Plymouth

**Country:** United States

**Facility:** Headlands Eastern MA LLC

**State:** Massachusetts

**Zip:** 02360

**Location 27:**

**City:** Ann Arbor

**Country:** United States

**Facility:** University of Michigan, Ann Arbor

**State:** Michigan

**Zip:** 48105

**Location 28:**

**City:** Rochester

**Country:** United States

**Facility:** Mayo Clinic, Rochester

**State:** Minnesota

**Zip:** 55905

**Location 29:**

**City:** Saint Louis

**Country:** United States

**Facility:** Washington University, St. Louis

**State:** Missouri

**Zip:** 63108

**Location 30:**

**City:** Las Vegas

**Country:** United States

**Facility:** Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas

**State:** Nevada

**Zip:** 89101

**Location 31:**

**City:** New York

**Country:** United States

**Facility:** Mount Sinai School of Medicine

**State:** New York

**Zip:** 10029

**Location 32:**

**City:** New York

**Country:** United States

**Facility:** Columbia University

**State:** New York

**Zip:** 10032

**Location 33:**

**City:** Rochester

**Country:** United States

**Facility:** University of Rochester Medical Center

**State:** New York

**Zip:** 14620

**Location 34:**

**City:** Winston-Salem

**Country:** United States

**Facility:** Wake Forest University Health Sciences

**State:** North Carolina

**Zip:** 27157

**Location 35:**

**City:** Beachwood

**Country:** United States

**Facility:** Case Western Reserve University

**State:** Ohio

**Zip:** 44122

**Location 36:**

**City:** Columbus

**Country:** United States

**Facility:** Ohio State University

**State:** Ohio

**Zip:** 43210

**Location 37:**

**City:** Tulsa

**Country:** United States

**Facility:** Central States Research

**State:** Oklahoma

**Zip:** 74136

**Location 38:**

**City:** Philadelphia

**Country:** United States

**Facility:** University of Pennsylvania

**State:** Pennsylvania

**Zip:** 19104

**Location 39:**

**City:** Providence

**Country:** United States

**Facility:** Butler Hospital Memory and Aging Program

**State:** Rhode Island

**Zip:** 02906

**Location 40:**

**City:** Charleston

**Country:** United States

**Facility:** Ralph H. Johnson VA Health Care System

**State:** South Carolina

**Zip:** 29401

**Location 41:**

**City:** Nashville

**Country:** United States

**Facility:** Vanderbilt University Medical Center Center for Cognitive Medicine

**State:** Tennessee

**Zip:** 37212

**Location 42:**

**City:** Dallas

**Country:** United States

**Facility:** University of Texas, Southwestern MC at Dallas

**State:** Texas

**Zip:** 75390

**Location 43:**

**City:** Houston

**Country:** United States

**Facility:** Baylor College of Medicine

**State:** Texas

**Zip:** 77030

**Location 44:**

**City:** Houston

**Country:** United States

**Facility:** Houston Methodist Neurological Institute

**State:** Texas

**Zip:** 77030

**Location 45:**

**City:** San Antonio

**Country:** United States

**Facility:** University of Texas Health Science Center at San Antonio

**State:** Texas

**Zip:** 78229

**Location 46:**

**City:** Norfolk

**Country:** United States

**Facility:** Eastern Virginia Medical School

**State:** Virginia

**Zip:** 23510

**Location 47:**

**City:** Richmond

**Country:** United States

**Facility:** National Clinical Research Inc.

**State:** Virginia

**Zip:** 23294

**Location 48:**

**City:** Seattle

**Country:** United States

**Facility:** University of Washington, Memory and Brain Wellness Center

**State:** Washington

**Zip:** 98195

**Location 49:**

**City:** Madison

**Country:** United States

**Facility:** University of Wisconsin

**State:** Wisconsin

**Zip:** 53792

#### Overall Officials

**Official 1:**

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

**Name:** Paul Aisen, MD

**Role:** STUDY_DIRECTOR

**Official 2:**

**Affiliation:** Brigham and Women's Hospital and Massachusetts General Hospital

**Name:** Reisa Sperling, MD

**Role:** STUDY_DIRECTOR

### References Module

#### See Also Links

**Label:** Alzheimer's Clinical Trials Consortium

**URL:** https://www.actcinfo.org/

**Label:** Alzheimer's Therapeutic Research Institute

**URL:** https://atri.usc.edu/

**Label:** APEX Study Home Page

**URL:** https://www.actcinfo.org/alzheimers-plasma-extension-apex-study/

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000003704

- Term: Dementia

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000024801

- Term: Tauopathies

- ID: D000019636

- Term: Neurodegenerative Diseases

- ID: D000019965

- Term: Neurocognitive Disorders

- ID: D000001523

- Term: Mental Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M3885

- Name: Alzheimer Disease

- Relevance: HIGH

- As Found: Alzheimer's Disease

- ID: M6904

- Name: Dementia

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M23002

- Name: Tauopathies

- Relevance: LOW

- As Found: Unknown

- ID: M21558

- Name: Neurodegenerative Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M21836

- Name: Neurocognitive Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: T2192

- Name: Familial Alzheimer Disease

- Relevance: HIGH

- As Found: Alzheimer's Disease

### Condition Browse Module - Meshes

- ID: D000000544

- Term: Alzheimer Disease

### Misc Info Module

- Version Holder: 2024-05-31
