ACP-204 in Adults With Alzheimer's Disease Psychosis

Study Overview
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Brief Summary
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This is a master protocol for 3 independent, seamlessly enrolling, multicenter, randomized, double-blind, placebo-controlled, parallel-group studies in patients with ADP Substudy 1 (Phase 2) will evaluate efficacy and dose response of ACP-204 30 and 60 mg vs placebo. This substudy will be initiated first. Substudies 2A and 2B (both: Phase 3) will be confirmatory studies of either both doses (ACP-204 30 and 60 mg, respectively) or a single dose from Part 1 vs placebo. Substudies 2A and 2B will be performed independently of each other and will commence after enrollment of Part 1. All 3 substudies will be analyzed independently of each other. Each substudy individually will consist of a screening period (up to 42 days); a double-blind treatment period (6 weeks); a safety follow-up period (30 days) for patients not rolling over into an open-label extension study; and vital status follow-up (for patients who terminated their substudy early).

Official Title
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A Master Protocol for Three Independent, Seamlessly Enrolling, Double-blind, Placebo-controlled Efficacy and Safety Studies of ACP-204 in Adults With Alzheimer's Disease Psychosis

Conditions
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Alzheimer's Disease Psychosis

Intervention / Treatment
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* Drug: ACP-204
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is male or female and ≥55 and ≤95 years of age living in the community or in an institutionalized setting Meets clinical criteria for possible or probable AD based on the 2011 National Institute on Aging-Alzheimer Association (NIA-AA) criteria Meets the revised criteria for psychosis in major or mild neurocognitive disorder established by the International Psychogeriatrics Association (IPA) Has either blood-based biomarker or documented evidence (e.g. positron emission tomography, cerebrospinal fluid biomarker) indicating amyloid plaque deposition and neuropathologic change consistent with AD Has a prior magnetic resonance imaging or computed tomography scan of the brain that is consistent with the diagnosis of AD Meets revised criteria for psychosis in major or mild neurocognitive disorder as per International Psychogeriatrics Association MMSE score ≥6 and ≤24 Psychotic symptoms for at least 2 months Lives in a stable place of residence and there are no plans to change living arrangements Has a designated study partner/caregiver Able to complete all study visits with a study partner/caregiver Must be on a stable dose of cholinesterase inhibitor or memantine, if applicable Exclusion Criteria: Requires treatment with a medication prohibited by the protocol Is in hospice and receiving end-of-life palliative care, or has become bedridden Requires skilled nursing care Psychotic symptoms that are primarily attributable to delirium, substance abuse, or a medical or psychiatric condition other than dementia Known history of cerebral amyloid angiopathy, epilepsy, central nervous system neoplasm, or unexplained syncope Atrial fibrillation Symptomatic orthostatic hypotension Protocol-defined exclusionary clinical laboratory findings Additional inclusion/exclusion criteria apply. Subjects will be evaluated at screening to ensure that all criteria for study participation are met.

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 95 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ACP-204 30 mg<br>Administration once daily at approximately the same time of day, with or without food | Drug: ACP-204<br>* ACP-204 is a potent and selective antagonist/inverse agonist of 5-hydroxytryptamine (serotonin) receptor subtype 2A.<br>|
| Experimental: ACP-204 60 mg<br>Administration once daily at approximately the same time of day, with or without food | Drug: ACP-204<br>* ACP-204 is a potent and selective antagonist/inverse agonist of 5-hydroxytryptamine (serotonin) receptor subtype 2A.<br>|
| Placebo Comparator: Placebo<br>Administration once daily at approximately the same time of day, with or without food | Drug: Placebo<br>* ACP-204 matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions subscales (SAPS-H+D) total score change from baseline (Substudies 1, 2A, 2B) | The SAPS-H+D subscales are a measure of two psychotic symptoms: hallucinations and delusions. The SAPS-H+D total score is the sum of the scores of the Hallucinations and Delusions subscales. The hallucinations domain score (SAPS-H) is the sum of the 7 hallucinations item scores, and the delusions domain core (SAPS-D) is the sum of the 13 delusions item scores. | From baseline to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression-Improvement in the ADP context (CGI-I-ADP) score | The CGI-I scale is a clinician-rated, 7-point scale used to rate the improvement in symptoms at the time of assessment, relative to the symptoms at Baseline. The CGI-I-ADP scale is the CGI-I scale applied in the ADP context, in which hallucinations and delusions are the symptoms of interest. | Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease psychosis, Hallucinations, Delusions