EMBARK: A Phase 3b, Open-Label, Single-Arm, Safety Study to Evaluate the Long-Term Safety and Efficacy of Aducanumab in Eligible Participants With Alzheimer’s Disease
Carmen Castrillo-Viguera1, Spyros Chalkias1, Patrick Burkett1, Shuang Wu1, Huaihou Chen1, Katie Harrison1, Carol Yurgalevitch1, Samantha Budd Haeberlein1
1Biogen
Objective:
We describe the design of EMBARK, a Phase 3b re-dosing study of aducanumab in participants with Alzheimer’s disease (AD). 
Background:
Aducanumab is a human monoclonal antibody selective for aggregated amyloid beta. On March 21, 2019, all aducanumab clinical trials were terminated following a pre-specified futility interim analysis of the Phase 3 studies, EMERGE and ENGAGE. Further analyses of the Phase 3 studies were conducted post-futility announcement using data from all randomized and dosed participants collected through April 1, 2019 with data after March 20, 2019 censored for efficacy analysis. In this final dataset, EMERGE met the pre-specified primary and secondary endpoints. Post-hoc analyses of data from a subset of patients exposed to high-dose aducanumab in ENGAGE support the findings of EMERGE. 
Design/Methods:

EMBARK is an open-label, single arm clinical safety study (NCT04241068) with a 24-month treatment period assessing the long-term safety and efficacy of aducanumab in participants with AD who were actively participating in the aducanumab clinical studies PRIME, EVOLVE, EMERGE, or ENGAGE at the time of discontinuation.

Participants will be titrated to receive 10 mg/kg aducanumab by intravenous infusion every 4 weeks. The study includes an approximately 8-week screening period, a 100-week treatment period and an 18-week safety and follow-up visit after the last dose.

The primary objective of EMBARK is to evaluate the long-term safety and tolerability of aducanumab. The primary endpoints are number of participants with adverse events (AEs), serious AEs, AEs leading to treatment discontinuation or study withdrawal, amyloid-related imaging abnormality-edema or amyloid-related imaging abnormality-hemorrhage or superficial siderosis, and number of participants with anti-aducanumab antibodies.

Results:

EMBARK is currently enrolling.

Conclusions:

EMBARK is expected to be one of the largest clinical trials in AD, with a planned enrollment of 2400 participants. EMBARK will provide further information on the long-term safety and efficacy of aducanumab.