Landscape of Phase II Trials in Alzheimer’s Disease

Abstract

Background: Drug development in Alzheimer’s disease (AD) over the past two decades has had high rates of failure. Novel trial designs, such as adaptive designs, have the potential to improve the efficiency of drug development in AD. Objective: To evaluate the design characteristics, temporal trends, and differences in design between sponsor types in phase II trials of investigational agents in AD. Methods: Phase I/II, II, and II/III trials for AD with drug or other biological interventions registered from December 1996 to December 2021 in ClinicalTrials.gov were included. Descriptive statistics were used to summarize trial characteristics. Linear, logistic, and multinomial regression models assessed temporal trends and differences between sponsor types in design characteristics. Results: Of N = 474 trials identified, randomized parallel group design was the most common design (72%). Only 12 trials (2.5%) used an adaptive design; adaptive features included early stopping rules, model-based dose-finding, adaptive treatment arm selection, and response adaptive randomization. The use of non-randomized parallel-group and open-label single arm designs increased over time. No temporal trend in the use of adaptive design was identified. Trials sponsored by industry only were more likely to use a randomized parallel-group design and have a larger estimated sample size than trials with other sponsor types. Conclusion: Our systematic review showed that very few phase II trials in AD used an adaptive trial design. Innovation and implementation of novel trial designs in AD trials can accelerate the drug development process.