TRAILBLAZER-ALZ 2: A Phase 3 Study to Assess Safety and Efficacy of Donanemab in Early Symptomatic Alzheimer’s Disease (P18-3.005)

Objective: We present baseline characteristics of TRAILBLAZER-ALZ 2 (NCT04437511), a global phase 3 study designed to assess the treatment effects of donanemab on disease progression in individuals with early symptomatic AD. Background: Donanemab is an antibody that targets N3pG, a modified form of amyloid-β (Aβ). TRAILBLAZER-ALZ (NCT03367403) was a phase 2 study of 272 individuals with early symptomatic Alzheimer’s disease (AD) with elevated amyloid plaque levels and intermediate tau levels on positron-emission tomography (PET). In TRAILBLAZER-ALZ, donanemab resulted in a 32% slowing of disease progression at 76 weeks on the Integrated Alzheimer’s disease Rating Scale (iADRS, composite measure of cognition and function) with a reduction of 85 centiloids in amyloid plaque level. Design/Methods: TRAILBLAZER-ALZ 2 is a randomized, placebo-controlled, double-blind study with a planned enrolment of ~1500 participants. The study population comprises individuals 60–85 years of age, with mild cognitive impairment or mild dementia due to AD, and the presence of both brain amyloid plaque and tau pathology (intermediate or high level). The primary analysis will test the intermediate tau pathology population. Participants were randomized 1:1 to placebo every 4 weeks (Q4W) or to donanemab 700mg IV Q4W for 3 doses and then 1400mg IV Q4W, with a potential blinded dose reduction to placebo based on amyloid plaque clearance at 24 and 52 weeks. The primary endpoint is change from baseline to 76 weeks on the iADRS; secondary endpoints include changes in other cognitive assessments, amyloid PET, tau PET, and volumetric MRI. Results: Available enrollment and baseline findings will be presented. Conclusions: Available enrollment and baseline findings will be presented. Disclosure: Dr. Zimmer has received personal compensation for serving as an employee of Eli Lilly & Company. Dr. Zimmer has received stock or an ownership interest from Eli Lilly & Company. Dr. Solomon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Solomon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Solomon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cognito. Dr. Solomon has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Solomon has received publishing royalties from a publication relating to health care. Dr. Evans has received personal compensation for serving as an employee of Eli Lilly & Company. Dr. Evans has received stock or an ownership interest from Eli Lilly & Company. Ming Lu has received personal compensation for serving as an employee of Eli Lilly and Company. Ming Lu has received stock or an ownership interest from Eli Lilly and Company. Dr. Sims has received personal compensation for serving as an employee of Eli Lilly and Company. Dr. Sims has received stock or an ownership interest from Eli Lilly and Company. An immediate family member of Dr. Brooks has received personal compensation for serving as an employee of Indiana Hospital Association. Dr. Brooks has received stock or an ownership interest from Eli Lilly and Company. Dr. Mintun has received personal compensation for serving as an employee of Eli Lilly & Co.