A total of 77 patients randomized to either ATH-1017 or placebo will be evaluated for improvements in cognition, global, and functional assessments across a 26-week treatment period.
The phase 2 ACT-AD clinical trial (NCT04491006) evaluating Athira Pharma’s investigational agent ATH-1017 in patients with mild-to-moderate Alzheimer disease (AD), has completed enrollment, with results expected to be announced in the first half of 2022, according to the company.1
This ongoing randomized, double-blind, placebo-controlled, 26-week trial will assess ATH-1017, a positive modulator of hepatocyte growth factor (HGF)/MET, in the treatment of 77 patients across 14 sites in the United States and Australia. Patients were randomized 1:1:1 to 1 of 2 dose groups of daily subcutaneous ATH-1017 or placebo and will continue to be evaluated for improvements in cognition, global, and functional assessments.
"The completion of enrollment in our ACT-AD trial is an important step forward in advancing ATH-1017 as a potential new treatment option for patients suffering from Alzheimer’s and other dementias," Mark Litton, PhD, MBA, president and chief executive officer, Athira, said in a statement.1 "We look forward to building on this momentum and sharing topline results from this Phase 2 trial in the first half of 2022. As part of our overall clinical development program to maximize the full potential of ATH-1017, we plan to initiate a clinical trial in Parkinson's disease dementia later this year. At Athira, we are committed to improving the lives of patients and their caregivers, and we are proud of our progress towards this goal to date."
Event-Related-Potential (ERP P300), a functional measure of working memory processing speed, will be measured through electroencephalogram (EEG). EEG will also be used to measure quantitative EEG (qEEG). Patients who complete the 26-week treatment period during ACT-AD or LIFT-AD (NCT04488419), Athira’s other ongoing clinical trial of ATH-1017, may enter an open-label extension period in which they receive the study drug at a high dose of 70 mg/day for an additional 26 weeks.
Hans Moebius, MD, PhD, chief medical officer, Athira, said in a statement that, "the completion of enrollment in ACT-AD is an important clinical milestone for Athira. Results from this trial may provide Athira with supportive information that can help optimize our ongoing potentially pivotal LIFT-AD trial and confirm the statistically significant improvement in P300 latency, a functional measure of working memory processing speed, demonstrated in our early trial."
LIFT-AD initiated dosing in October 2020 and enrolled up to 300 patients with mild-to-moderate AD.2 That trial is currently investigating ATH-1017’s efficacy in terms of cognitive improvements and performance on global/functional assessments between placebo and treatment groups.
ATH-1017, which is designed to enhance HGF to promote brain health and function, has shown positive results in preclinical trials to date. In an animal model of APP1/PS1 transgenic mice, treatment with ATH-1017 resulted in increased qEEG γ power that is associated with cognitive processing and memory.
The investigational agent also demonstrated safety, including no serious adverse events, in a phase 1a/b clinical trial of healthy young, healthy elderly, and patients with AD. Additionally, it also showed a statistically significant improvement in ERP, and investigators noted ERP 300 latency among patients after multiple treatments with ATH-1017 compared with placebo (P <.05).
Moebius went on to state, "the pathophysiology of Alzheimer’s disease is complex and includes not only the hallmarks of beta-amyloid deposits and neurofibrillary tangles, but neuroinflammation, vascular dysfunction, and neurodegeneration. By focusing on neuronal network recovery, ATH-1017’s novel mechanism of action is agnostic to the underlying disease pathology of Alzheimer’s and other dementias."1