Preclinical Alzheimer's Disease, Early Preclinical Alzheimer's Disease
Conditions
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)
Interventions
RADIATIONNAV4694
Amyloid PET imaging with NAV4694 injection
Sponsors
Alzheimer's Clinical Trials Consortium (ACTC)
Alzheimer's Therapeutic Research Institute
Alzheimer's Association
University of Southern California
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
55 Years to 80 Years
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Baseline, Month 12, Month 24, Month 36 and Month 48 | Assess longitudinal changes from initial visit in plasma phosphorylated tau (ptau) 217 ratio using a proteomics assay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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). |
| Rate of Change from Baseline to Month 48 as measured Cognitive Function Index (CFI) | Baseline, Month 12, Month 24, Month 36 and Month 48 | 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. |
Other
| Measure | Time frame |
|---|---|
| Collection of baseline amyloid PET on participants without prior amyloid PET data | Baseline |
Countries
United States
Outcome results
None listed