221AD302 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

2015-09-15

Primary completion

2019-08-05

Completion

2019-08-05

Outcome

Met 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 High Dose (PC Period); p = 0.0120; Difference -0.39 (95% CI -0.694 to -0.086); MMRM NCT02484547 ↗

Publications

• Cummings J, Cohen S, Murphy J, Brothers HM, Nejati M, Forrestal F, de Moor C, O'Gorman J, Harrison J, Jaeger J, Mummery CJ, Porsteinsson AP, Potashman M, Tian Y, Yang L, He P, Haeberlein SB. Evaluation of cognitive, functional, and behavioral effects observed in EMERGE, a phase 3 trial of aducanumab in people with early Alzheimer's disease. Alzheimers Dement. 2025 Jun;21(6):e70224. doi: 10.1002/alz.70224.
• Burton J, Brothers HM, Hutchison RM, Murphy J, Sun T, Dent G, Curiale G, Kowalski K. Lower baseline amyloid beta burden is associated with greater percent of amyloid beta positron emission tomography reduction and better clinical outcomes in the aducanumab Phase 3 trials ENGAGE and EMERGE in early Alzheimer's disease. J Prev Alzheimers Dis. 2025 Aug;12(7):100202. doi: 10.1016/j.tjpad.2025.100202. Epub 2025 May 24.
• 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	10 mg/kg	Intravenous

Indications