Baseline Characteristics from Evoke and Evoke+: Two Phase 3 Randomized Placebo-controlled Trials of Oral Semaglutide in Patients with Early Alzheimer's Disease
Philip Scheltens1, Alireza Atri2, Howard Feldman3, Oskar Hansson4, Filip Knop5, Mary Sano6, Claus Dethlefsen7, Peter Johannsen7, Teresa León7, Charlotte Thim Hansen7, Jeffrey Cummings8
1Alzheimer Centre, VU University Medical Center Amsterdam, 2Banner Sun Health Research Institute; Banner Alzheimer’s Institute; Brigham and Women’s Hospital, Harvard Medical School, 3Alzheimer’s Disease Cooperative Study, Department of Neurosciences, University of California San Diego, 4Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University; Memory Clinic, Skåne University Hospital, 5Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen; Steno Diabetes Center Copenhagen; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 6Icahn School of Medicine at Mount Sinai, James J Peters VAMC, 7Novo Nordisk A/S, 8University of Nevada
Objective:
We report the preliminary baseline characteristics in the ongoing phase 3 evoke and evoke+ trials investigating the safety and efficacy of oral semaglutide for early AD.
Background:
Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), is approved for use in type 2 diabetes (T2D) or obesity.
Design/Methods:
evoke (NCT04777396) and evoke+ (NCT04777409) are multicenter, randomized, double-blind, placebo-controlled trials. Eligible individuals were 55–85 years, amyloid-positive, with mild cognitive impairment (MCI) due to AD and Mini-Mental State Examination (MMSE) score ≥22. Participants were randomized 1:1 to once-daily oral semaglutide 14 mg (titrated from 3 mg for the initial 4 weeks and 7 mg for the following 4 weeks) or placebo plus standard of care for 156 weeks (104 weeks + 52-week extension). The primary endpoint is change in the CDR – Sum of Boxes (CDR-SB). Baseline characteristics of enrolled patients were compiled after completion of enrollment on September 8, 2023. Trials are ongoing, data may be subject to minor changes until database lock.
Results:
evoke and evoke+ enrolled 1,855 and 1,835 participants each; data from 118 randomized participants from evoke+ are not included here. Mean (SD) age was 71.8 (7.1) and 72.6 (7.1) years; 53.0% and 51.8% of participants were female; most participants (76.6%) were White; 59.7% and 54.5% were in receipt of AD medication. Mean (SD) CDR-SB score was 3.7 (1.5) and 3.7 (1.6); ADCS-ADL-MCI score was 39.4 (7.3) and 38.9 (7.5); 72.5% and 68.7% of participants had a CDR global score of 0.5.
Conclusions:
evoke and evoke+ are the first large-scale phase 3 trials to investigate the disease-modifying potential of semaglutide in early AD. Both studies recruited a very similar population.