Objective:

To provide an overview of key decentralized design characteristics utilized in the TRAILBLAZER-ALZ 3 (TB3) (NCT05026866) study, an ongoing Phase 3 research trial with a decentralized design, testing donanemab in preclinical Alzheimer’s disease (AD).

Background:

Decentralized trials (DCTs) offer flexibility typically limited in traditional trial design, which may increase geographical and ethnic/racial diversity in trial populations, improve participant engagement and retention, and reduce trial cost. Clinical trials focused on AD pose specialized challenges to remotely assessing cognitive outcomes.

Design/Methods:

TRAILBLAZER-ALZ 3 is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial designed to assess the impact of donanemab versus placebo in cognitively unimpaired participants with evidence of AD pathology.

Results:

The remote screening process, which includes mobile research units and health fairs, uses the modified Telephone Interview for Cognitive status (TICS-m) to help select for cognitively unimpaired individuals. Plasma AD assays assess an AD biomarker as part of the inclusion screening criteria and minimize participant burden. Optional remote genetic counseling for APOE disclosure is offered as well as two optional sub-studies testing amyloid PET and tau PET. Clinical outcomes are assessed throughout the study using central raters who administer the Clinical Dementia Rating scale (CDR) to study partners and participants, and psychometric examinations to study participants. Self-administered tests are proctored remotely by a centralized study coordinator who also helps coordinate and facilitate all remote appointments for the participant and study partner. Infusion and imaging centers outside of traditional study "sites" are available to improve participant convenience and access throughout the study.

Conclusions:

TRAILBLAZER-ALZ 3 represents an innovative design that could potentially pave the way for future AD clinical studies by utilizing decentralized trial design with central raters, time-to-clinical-event model, blood-based AD biomarker selection criterion, and limited dosing of anti-amyloid antibody.