Phase 2/3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of EXV-802 and EXV-801 in Participants with Agitation in Alzheimer’s Disease

The primary objective is to evaluate the therapeutic change from baseline of EXV-802 compared with placebo in the treatment of agitation associated with Alzheimer's disease dementia. 5

Secondary objectives include:

• Evaluation of the clinical importance of the therapeutic change from baseline of EXV-802 compared with placebo.
• Assessment of therapeutic changes related to caregiver distress resulting from agitation and aggression.
• Evaluation of therapeutic changes related to irritability or lability.
• Assessment of therapeutic changes related to sleep disorders.
• Evaluation of safety and tolerability for EXV-802.
• Evaluation of the therapeutic change from baseline of EXV-801 monotherapy compared with placebo.
• Evaluation of safety and tolerability for EXV-801 monotherapy.

This clinical trial involves a total of 102 participants. The study population consists of male and female adults between the ages of 55 and 90 years. All subjects have a previously established diagnosis of Alzheimer's disease dementia. The included individuals must present with at least moderate agitation that requires pharmacological intervention. Eligible participants are able to maintain mobility independently, through the use of a walker, or via a wheelchair.

This Phase 2/3, double-blind, placebo-controlled study is designed to evaluate the safety and efficacy of EXV-802 and EXV-801 in treating agitation associated with Alzheimer’s disease dementia. The primary objective is to assess the therapeutic change from baseline of EXV-802 compared to a matching placebo. Participants are evaluated using the Cohen-Mansfield Agitation Inventory total score as the primary endpoint at Week 6. Secondary endpoints include assessments via the Clinical Global Impression of Severity of Illness score, the NPI-C Caregiver Distress total score, irritability, lability, and sleep disorders. Safety is monitored through the Mini-Mental State Examination, the Columbia Suicide Severity Rating Scale, clinical laboratory values, vital signs, electrocardiograms, and physical examination findings. The study involves a screening period to confirm eligibility based on age, mobility, and diagnosis, followed by a treatment phase lasting until the end-of-study visit at Week 6. The total estimated duration of the study, including recruitment, is from May 2026 to January 2029.

EXV-802 is an experimental medication containing dextromethorphan and deramciclane fumarate. This substance is administered in a capsule pharmaceutical form via the oral route.

EXV-801 is an experimental medication containing deramciclane. The administration of this capsule is performed through the oral route at a dosage of 60 mg.

A matching placebo is utilized as a comparator in this study.

The primary efficacy endpoint is the difference between the active treatment and placebo, determined by changes from baseline to Week 6 in the Cohen-Mansfield Agitation Inventory total score for agitation in Alzheimer’s disease dementia.

Secondary efficacy assessments for EXV-802 include the following measurements at Week 6:

• Changes in the Clinical Global Impression of Severity of Illness score related to agitation symptoms.
• Changes in the Neuropsychiatric Inventory-Caregiver total score for agitation and aggression.
• Changes in the Neuropsychiatric Inventory-Caregiver irritability and lability score.
• Changes in the Neuropsychiatric Inventory-Caregiver sleep disorders score.

Secondary efficacy assessments for EXV-801 include the following measurements at Week 6:

• Changes in the Cohen-Mansfield Agitation Inventory.
• Changes in the Clinical Global Impression of Severity of Illness score.
• Changes in the Neuropsychiatric Inventory-Caregiver.
• Changes in exploratory Parkinsonian disease markers, specifically brain-derived neurotrophic factor.
• Changes in blood-based biomarkers.