221AD301 Phase 3 Study of Aducanumab (BIIB037) in Early Alzheimer's Disease

Summary

The primary objective of the study is to evaluate the efficacy of monthly doses of aducanumab in slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score as compared with placebo in participants with early AD. Secondary objectives are to assess the effect of monthly doses of aducanumab as compared with placebo on clinical progression as measured by Mini-Mental State Examination (MMSE), AD Assessment Scale-Cognitive Subscale (13 items) \[ADAS-Cog 13\], and AD Cooperative Study-Activities of Daily Living Inventory (Mild Cognitive Impairment version) \[ADCS-ADL-MCI\].

Timeline

Start

2015-08-13

Primary completion

2019-08-08

Completion

2019-08-08

Outcome

Missed primary endpoint

Stopped: “Study was discontinued based on futility analysis done and not based on safety concerns. Follow-up visits and closing out study activities are completed”

registry analysis (superiority test); Placebo (PC Period) vs BIIB037 Low Dose (PC Period); p = 0.2250; Difference from Placebo 0.110 (95% CI -0.469 to 0.403); MMRM Model NCT02477800 ↗

registry analysis (superiority test); Placebo (PC Period) vs BIIB037 High Dose (PC Period); p = 0.8330; Difference from late start group 0.03 (95% CI -0.262 to 0.326); MMRM Model NCT02477800 ↗

Publications

• Loomis SJ, Miller R, Castrillo-Viguera C, Umans K, Cheng W, O'Gorman J, Hughes R, Budd Haeberlein S, Whelan CD. Genome-Wide Association Studies of ARIA From the Aducanumab Phase 3 ENGAGE and EMERGE Studies. Neurology. 2024 Feb 13;102(3):e207919. doi: 10.1212/WNL.0000000000207919. Epub 2023 Dec 28.
• Muralidharan KK, Kowalski KG, Tong X, Haeberlein SB, Rajagovindan R, Nestorov I. Characterization of exposure-Clinical Dementia Rating-Sum of Boxes relationship in subjects with early Alzheimer's disease from the aducanumab Phase 3 trials. J Pharmacokinet Pharmacodyn. 2023 Feb;50(1):45-62. doi: 10.1007/s10928-022-09839-3. Epub 2023 Jan 4.
• Salloway S, Chalkias S, Barkhof F, Burkett P, Barakos J, Purcell D, Suhy J, Forrestal F, Tian Y, Umans K, Wang G, Singhal P, Budd Haeberlein S, Smirnakis K. Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease. JAMA Neurol. 2022 Jan 1;79(1):13-21. doi: 10.1001/jamaneurol.2021.4161.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Aducanumab	Monoclonal antibody	—	Intravenous

Indications