ACU193, a Monoclonal Antibody that Selectively Binds Soluble Aß Oligomers: Development Rationale, Phase 1 Trial...

Area of Science:

• Neuroscience
• Pharmacology
• Clinical Trials

Background:

• Alzheimer's disease (AD) presents a significant unmet medical need, necessitating earlier assessment of disease-related outcomes in clinical trials.
• ACU193 is a novel monoclonal antibody targeting toxic amyloid beta (Aβ) oligomers, implicated in early AD pathogenesis.
• Nonclinical studies suggest ACU193 can mitigate the detrimental effects of Aβ oligomers.

Purpose of the Study:

• To design a Phase 1 study evaluating target engagement and incorporating innovative measures for accelerated development of a potential disease-modifying Alzheimer's treatment.
• To gather data for a go/no-go decision on initiating a Phase 2/3 study for ACU193.

Main Methods:

• The INTERCEPT-AD trial is a randomized, placebo-controlled Phase 1a/b study in early AD patients (mild cognitive impairment/dementia).
• ACU193 was administered intravenously at doses ranging from 2-60 mg/kg.
• Assessments included safety (MRI for ARIA), tolerability, pharmacokinetics, target engagement, clinical outcomes (ADAS-Cog, CDR-SB), and novel digital/imaging biomarkers (cognitive tests, arterial spin labeling MRI).

Main Results:

• A Phase 1 study design was successfully developed for ACU193.
• The design facilitates data collection crucial for deciding on the initiation of a subsequent adaptive Phase 2/3 study.

Conclusions:

• A Phase 1a/b trial and clinical development plan for an Alzheimer's disease therapeutic can be designed to ensure patient safety.
• The integration of novel biomarkers and adaptive study designs allows for informed decision-making and accelerated timelines in Alzheimer's drug development.