Results from the long-term extension of PRIME: A randomized Phase 1b trial of aducanumab

Abstract

Introduction: Aducanumab selectively targets aggregated forms of amyloid beta (Aβ), a neuropathological hallmark of Alzheimer's disease (AD).

Methods: PRIME was a Phase 1b, double-blind, randomized clinical trial of aducanumab. During the 12-month placebo-controlled period, participants with prodromal AD or mild AD dementia were randomized to receive aducanumab or placebo. At week 56, participants could enroll in a long-term extension (LTE), in which all participants received aducanumab. The primary endpoint was safety and tolerability.

Results: Amyloid-related imaging abnormalities-edema (ARIA-E) were the most common adverse event. Dose titration was associated with a decrease in the incidence of ARIA-E. Over 48 months, aducanumab decreased brain amyloid levels in a dose- and time-dependent manner. Exploratory endpoints suggested a continued benefit in the reduction of clinical decline over 48 months.

Discussion: The safety profile of aducanumab remained unchanged in the LTE of PRIME. Amyloid plaque levels continued to decrease in participants treated with aducanumab.

Highlights: PRIME was a Phase 1b, double-blind, randomized clinical trial of aducanumab. We report cumulative safety and 48-month efficacy results from PRIME. Amyloid-related imaging abnormalities-edema (ARIA-E) were the most common adverse event (AE); 61% of participants with ARIA-E were asymptomatic. Dose titration was associated with a decrease in the incidence of ARIA-E. Aducanumab decreased levels of amyloid beta (Aβ) in a dose- and time-dependent manner.

Trial registration: ClinicalTrials.gov NCT01677572.

Keywords: Alzheimer's disease; PRIME; aducanumab; amyloid‐related imaging abnormalities; clinical trials.