Objective: To present the design for a study of ACP-204 efficacy and safety in adults with Lewy body dementia psychosis (LBDP), including Parkinson’s disease dementia psychosis (PDDP) and dementia with Lewy bodies psychosis (DLBP).
Background: Psychosis is a prevalent feature of LBD and PDD, affecting 20%-70% of patients depending on dementia type and disease stage. In addition to the increased morbidity/mortality of LBDP and the lack of approved treatments, patients can be treated with off-label antipsychotics associated with safety concerns. ACP-204 is a selective 5-HT2A (less so at 5-HT2C) inverse agonist/antagonist discovered to have an improved pharmacological profile compared with pimavanserin, which is approved for PDP.
Method: This is a multicenter, randomized, double-blind, placebo-controlled phase 2 study investigating the efficacy, dose response, and safety of ACP-204 60 or 30 mg in LBDP. Eligible patients include adults with LBDP and psychosis persisting ≥2 months prior to screening. PDD/DLB will be confirmed using established clinical criteria; α-synuclein will be measured but not required for inclusion. Participants will be randomized 1:1:1 to receive placebo, ACP-204 30 mg, or 60 mg for 6 weeks, with a 50% cap on randomization of patients with PDDP on all treatment groups and no cap for patients with DLBP. Target enrollment is ~180 participants, allowing for ~10% nonevaluable participants, providing ≥85% power to detect an effect size of 0.6 between ACP-204 30 or 60 mg and placebo at α=0.05 using a 2-sided test. Participants will be stratified by disease and study site. Those who complete the double-blind treatment period may be eligible to enroll in the open-label extension (OLE). The study will include a ≤30-day screening period, a 6-week double-blind treatment period, a 30-day safety follow-up (excludes OLE participants), and a mortality follow-up for participants with early study termination (Figure). The primary endpoint will be change from baseline to week 6 in the Scale for Assessment of Positive Symptoms (SAPS) for LBDP (equivalent to the SAPS-PDP).
Results: TBD
Conclusion: This will be the first clinical study to evaluate the efficacy and safety of ACP-204 in patients with LBDP, a population with considerable unmet needs.
Abstract Figure
To cite this abstract in AMA style:
R. Nunez, S. Friend, B. Howell, S. Pathak, B. Dirks, X. Feng, V. Abler. Design of the Phase 2, Double-Blind, Placebo-Controlled, Multicenter Study Investigating the Efficacy and Safety of ACP-204, a Novel 5-HT2A Inverse Agonist, in Adults With Lewy Body Dementia Psychosis [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/design-of-the-phase-2-double-blind-placebo-controlled-multicenter-study-investigating-the-efficacy-and-safety-of-acp-204-a-novel-5-ht2a-inverse-agonist-in-adults-with-lewy-body-dementia-psychosis/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/design-of-the-phase-2-double-blind-placebo-controlled-multicenter-study-investigating-the-efficacy-and-safety-of-acp-204-a-novel-5-ht2a-inverse-agonist-in-adults-with-lewy-body-dementia-psychosis/