A Study to Evaluate Safety, Tolerability, and Efficacy of Lecanemab in Subjects With Early Alzheimer's Disease

Summary

This is a multinational, multicenter, double-blind, placebo-controlled, parallel-group study using a Bayesian design with response adaptive randomization across placebo or 5 active arms of lecanemab to determine clinical efficacy and to explore the dose response of lecanemab using a composite clinical score (ADCOMS). BAN2401-G000-201 Core study is an 18-month study in which 3 dose levels (2.5, 5, and 10 mg/kg) are given biweekly (once every 2 weeks) to separate groups of participants and 2 dose levels (5 and 10 mg/kg) are given monthly (once every 4 weeks) to separate groups of participants. Participants will be from 2 clinical subgroups: mild cognitive impairment (MCI) due to Alzheimer's disease (AD) or mild Alzheimer's disease dementia. Frequent interim analyses will be conducted to continually update randomization allocation on the basis of the primary clinical endpoint. Any participant who completes the study treatment (Visit 42 \[Week 79\] of the Core study) or discontinues the Core Study will be eligible to participate in the Extension Phase, provided they meet the Extension Phase inclusion and exclusion criteria. Participants will receive 10 mg/kg biweekly for up to 60 months or until the drug is commercially available in the country, where the subject resides, or until the benefit-to-risk ratio from treatment with lecanemab is no longer considered favorable, whichever comes first. The Follow-up Visit in the Extension Phase will take place 3 months after the last dose of study drug.

Timeline

Start

2012-12-20

Primary completion

2024-12-10

Completion

2024-12-10

Publications

• Devanarayan V, Ye Y, Zhu L, Tian L, Kramer L, Irizarry M, Dhadda S. Predicted natural progression as an Alzheimer's prognostic covariate improves the precision of lecanemab efficacy assessments and clinical trial efficiency. Alzheimers Dement. 2025 Mar;21(3):e70045. doi: 10.1002/alz.70045.
• Devanarayan V, Ye Y, Charil A, Andreozzi E, Sachdev P, Llano DA, Tian L, Zhu L, Hampel H, Kramer L, Dhadda S, Irizarry M; Alzheimer's Disease Neuroimaging Initiative (ADNI). Predicting clinical progression trajectories of early Alzheimer's disease patients. Alzheimers Dement. 2024 Mar;20(3):1725-1738. doi: 10.1002/alz.13565. Epub 2023 Dec 13.
• Berry DA, Dhadda S, Kanekiyo M, Li D, Swanson CJ, Irizarry M, Kramer LD, Berry SM. Lecanemab for Patients With Early Alzheimer Disease: Bayesian Analysis of a Phase 2b Dose-Finding Randomized Clinical Trial. JAMA Netw Open. 2023 Apr 3;6(4):e237230. doi: 10.1001/jamanetworkopen.2023.7230.
• McDade E, Cummings JL, Dhadda S, Swanson CJ, Reyderman L, Kanekiyo M, Koyama A, Irizarry M, Kramer LD, Bateman RJ. Lecanemab in patients with early Alzheimer's disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study. Alzheimers Res Ther. 2022 Dec 21;14(1):191. doi: 10.1186/s13195-022-01124-2.
• Dhadda S, Kanekiyo M, Li D, Swanson CJ, Irizarry M, Berry S, Kramer LD, Berry DA. Consistency of efficacy results across various clinical measures and statistical methods in the lecanemab phase 2 trial of early Alzheimer's disease. Alzheimers Res Ther. 2022 Dec 9;14(1):182. doi: 10.1186/s13195-022-01129-x.
• Swanson CJ, Zhang Y, Dhadda S, Wang J, Kaplow J, Lai RYK, Lannfelt L, Bradley H, Rabe M, Koyama A, Reyderman L, Berry DA, Berry S, Gordon R, Kramer LD, Cummings JL. A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-Abeta protofibril antibody. Alzheimers Res Ther. 2021 Apr 17;13(1):80. doi: 10.1186/s13195-021-00813-8.

Drugs

Indications