ALTITUDE-AD: Use of a Validated Plasma pTau217 Assay to Screen Potential Participants in an Ongoing Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Sabirnetug for Early Alzheimer's Disease
H Todd Feaster1, Karen Sundell1, Maddelyn Hyland1, Gopalan Sethuraman1, Vladimir Skljarevski1, June Kaplow1, Robert A. Dean1, Jasna Jerecic1, Eric Siemers1
1Acumen Pharmaceuticals, Inc
Objective:
To investigate using a plasma pTau217 assay to enrich the population of potential study participants with those likely to have brain amyloid burden sufficient for inclusion in a study of early symptomatic Alzheimer’s disease (AD).
Background:
Clinical AD trials screen and exclude many potential participants who do not meet criteria relating to amyloid pathology. In the phase 1 INTERCEPT-AD study of sabirnetug (ACU193), 75% of screened participants were ineligible, largely due to negative amyloid positron emission tomography (PET). Elevated plasma concentrations of pTau217 strongly suggest AD pathology; conversely, lower pTau217 concentrations may identify individuals who are likely to be ineligible based on subsequent amyloid PET or cerebrospinal fluid (CSF) Ab42/Ab40 ratio assessment, sparing potential participants unnecessary radiation or lumbar punctures (LPs).
Design/Methods:
ALTITUDE-AD (NCT06335173) is an ongoing 80-week, global, randomized, double-blind, placebo-controlled phase 2 study of sabirnetug in individuals with early AD and evidence of amyloid pathology. Blood is analyzed using the Fujirebio plasma pTau217 assay, a Lumipulse platform-based, research-use-only assay analytically and clinically validated as a Lab-Developed Test. During screening, individuals with pTau217 concentrations ≥0.15 pg/mL qualify for amyloid pathology testing using either amyloid PET or CSF Aβ42/Ab40 ratio to determine study eligibility. The pTau217 ≥0.15 pg/mL cut-point was designed for enrichment purposes and is not intended as a diagnostic cut-point.
Results:
Among participants screened to date, 48% had pTau217 plasma concentrations ≥0.15 pg/mL, of which 78% met study amyloid burden eligibility requirements after confirmatory testing of amyloid pathology. Of participants who underwent amyloid PET imaging or CSF testing, 79% and 62% met the amyloid burden inclusion criterion, respectively.
Conclusions:
The pTau217 enrichment strategy is performing as intended, reducing unnecessary amyloid PET scans or LP procedures for potential trial participants compared to INTERCEPT-AD, which did not use plasma pTau217 screening.
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