Safety and Efficacy of EXV-802 and EXV-801 in the Treatment of Agitation in Alzheimer's Disease Dementia (SERENADA)

Phase 2/3, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of EXV-802 and EXV-801 in the Treatment of Agitation in Participants With Alzheimer's Disease Dementia

The goal of this clinical trial is to evaluate the safety and efficacy of EXV-802 and EXV-801 in treatment of agitation in participants with Alzheimer's Disease dementia.

Study Overview

• Status: Recruiting
• Conditions: Agitation Associated With Alzheimer's Disease Dementia
• Intervention / Treatment: Drug: EXV-802; Drug: Placebo; Drug: EXV-801

Detailed Description

This is a Phase 2/3 multicenter, double-blind, placebo-controlled, three-arm, multicenter study evaluating the safety and efficacy of EXV-802 and EXV-801 in treatment of agitation in participants with Alzheimer's Disease dementia. The diagnosis of agitation will be based on the consensus definition for agitation in patients with cognitive disorders developed by te International Psychogeriatric Association (IPA) Agitation Definition Work Group as well as neuroimaging performed after onset of dementia symptoms and a Core 1 AD biomarker.

The study will be conducted at up to 60 centers in the US, Canada and Europe.. Screening will occur within approximately 4 weeks prior to randomization. Following screening procedures for assessment of inclusion and exclusion criteria, eligible participants will be randomized into the study. Approximately 100 patients per arm will be randomized (300 total).

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Exciva Clinical Studies; Phone Number: +49 6221-6479990; Email: studies@exciva.com

Study Locations

• Canada
  • Ontario
    • North York, Ontario, Canada, M4N 3M5
      • Not yet recruiting
      • Sunnybrook Health Sciences Centre
    • North York, Ontario, Canada, M6A 2E1
      • Not yet recruiting
      • Baycrest Centre for Geriatric Care
    • Peterborough, Ontario, Canada, K9H 294
      • Not yet recruiting
      • Kawartha Centre
    • Whitby, Ontario, Canada, L1N 5S9
      • Not yet recruiting
      • Ontario Shores Centre for Mental Health Sciences
• United Kingdom
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH12 5PJ
      • Recruiting
      • Scottish Brain Sciences
  • North East Scotland
    • Aberdeen, North East Scotland, United Kingdom, AB25 2XE
      • Recruiting
      • Scottish Brain Sciences
• United States
  • California
    • Murrieta, California, United States, 92562
      • Recruiting
      • Esperanza Clinical
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Recruiting
      • Josephson Wallack Munshower Neurology PC
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Recruiting
      • Precise Research Centers
  • New York
    • Brooklyn, New York, United States, 11229
      • Recruiting
      • Integrative Clinical Trials
    • New York, New York, United States, 10036
      • Recruiting
      • Manhattan Behavioral Medicine
  • Ohio
    • Independence, Ohio, United States, 44131
      • Recruiting
      • Insight Clinical Trials
  • Oregon
    • Portland, Oregon, United States, 97239
      • Not yet recruiting
      • Oregon Health & Science University
  • Vermont
    • Bennington, Vermont, United States, 05201
      • Not yet recruiting
      • The Memory Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. The participant is an adult male or female between the ages of 55 to 90 years inclusively, who can move around by themselves, with a walker or a wheelchair.
2. A previously established diagnosis of AD dementia.
3. The participant has clinically significant, moderate/severe agitation at the time of screening and for at least 2 weeks prior to randomization
4. The diagnosis of agitation must meet the International Psychogeriatric Association (IPA) provisional definition of agitation.
5. Caregiver who is able and willing to comply with all required study procedures and who is in contact with the participant at least on four individual days for at least two hours per day.

Exclusion criteria:

1. The participant has a confirmed primary diagnosis of a dementia-related disease other than AD dementia.
2. The participant has symptoms of agitation that are not secondary to AD dementia
3. The participant has a history of uncontrolled seizures or a history of epilepsy.
4. The participant has a major medical illness or unstable medical condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EXV-802; Participants will be assigned to treatment with EXV-802 capsules administered twice a day over a 6-week period.	Drug: EXV-802; Specified dose twice daily; Other Names: Dextromethorphan + EXV-801
Placebo Comparator: Placebo; Participants will be assigned to treatment with placebo capsules administered twice a day over a 6-week period.	Drug: Placebo; Specified dose twice daily
Experimental: EXV-801; Participants will be assigned to treatment with EXV-801 capsules administered twice a day over a 6-week period.	Drug: EXV-801; Specified dose twice daily; Other Names: deramciclane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline to endpoint (Week 6) in the Cohen-Mansfield Agitation Inventory - International Psychogeriatric Association (CMAI-IPA) score	The CMAI is used to assess the frequency of manifestations of agitated behaviors in elderly persons. It consists of 29 agitated behaviors that are further categorized into distinct agitation syndromes, also known as CMAI factors of agitation. These distinct agitation syndromes include aggressive behavior, physically nonaggressive behavior, and verbally agitated behavior. Each of the 29 items is rated on a 7-point scale of frequency (1 = never, 2 = less than once a week but still occurring, 3 = once or twice a week, 4 = several times a week, 5 = once or twice a day, 6 = several times a day, 7 = several times an hour). The ratings are based on the 2 weeks preceding assessment of the CMAI. Higher scores indicate higher frequency of agitated behaviors while lower scores indicate lower frequency of agitated behaviors The CMAI-IPA includes 19 items that were mapped to IPA agitation domains. The total score ranges from 19 to 133 with higher scores indicating more severity.	Baseline to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline to endpoint (Week 6) in the Clinical Global Impression of Severity of Illness (CGI-S) score as related to symptoms of agitation	The CGI-S is an observer-rated scale that measures illness severity. The CGI-S is a 7-point (1-7) scale (1 = normal, not at all ill; 7 = extremely ill) that assessed the severity of agitation in this study. Higher scores indicate severe agitation, while the lower scores indicate little or no agitation.	Baseline to Week 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline to endpoint (Week 6) in the Neuropsychiatric Inventory - Clinician (NPI-C) Caregiver Distress score for Agitation and Aggression domains	The NPI-C is a retrospective interview covering 14 neuropsychiatric symptom domains. The NPI-C version of the NPI scale was designed to be administered by the clinician to the participant and the caregiver. The caregiver is first asked to provide frequency, severity, and distress ratings for each individual item across the domains. Frequency is rated on a scale from 0 to 4. Severity is rated on a scale from 0 to 3. Separately, the rater interviews the patient to assess frequency (0 to 4) of each item. Clinician rating of clinical impression is a severity rating (0 to 3) based on all available clinical and interview information. For this endpoint, the caregiver distress will be analyzed for the agitation and aggression domains. Caregiver distress is rated on a scale from 0 to 5 with a total score range of 0 to 10 across the 2 domains. Higher scores indicate greater caregiver distress.	Baseline to Week 6
Changes from baseline to endpoint (Week 6) in the Neuropsychiatric Inventory - Clinician (NPI-C) Irritability/Liability Domain score	The NPI-C is a retrospective interview covering 14 neuropsychiatric symptom domains. The NPI-C version of the NPI scale was designed to be administered by the clinician to the participant and the caregiver. The caregiver is first asked to provide frequency, severity, and distress ratings for each individual item across the domains. Frequency is rated on a scale from 0 to 4. Severity is rated on a scale from 0 to 3. Separately, the rater interviews the patient to assess frequency (0 to 4) of each item. Clinician rating of clinical impression is a severity rating (0 to 3) based on all available clinical and interview information. The score for the irritability/lability domain is the sum of clinical impression ratings of all items. There are 12 items in the irritability/lability domain. The minimum score for the irritability/lability domain is 0 and maximum score per domain is 36, with higher scores indicate greater symptom severity.	Baseline to Week 6
Changes from baseline to endpoint (Week 6) in the Neuropsychiatric Inventory - Clinician (NPI-C) Sleep Disorders Domain score	The NPI-C is a retrospective interview covering 14 neuropsychiatric symptom domains. The NPI-C version of the NPI scale was designed to be administered by the clinician to the participant and the caregiver. The caregiver is first asked to provide frequency, severity, and distress ratings for each individual item across the domains. Frequency is rated on a scale from 0 to 4. Severity is rated on a scale from 0 to 3. Separately, the rater interviews the patient to assess frequency (0 to 4) of each item. Clinician rating of clinical impression is a severity rating (0 to 3) based on all available clinical and interview information. The score for the sleep disorders domain is the sum of clinical impression ratings of all items. There are 8 items in the sleep disorders domain. The minimum score for the sleep disorders domain is 0 and maximum score per domain is 24, with higher scores indicate greater symptom severity.	Baseline to Week 6

Collaborators and Investigators

• Sponsor: Exciva GmbH

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): February 1, 2029

Study Registration Dates

• First Submitted: November 27, 2025
• First Submitted That Met QC Criteria: December 8, 2025
• First Posted (Actual): December 16, 2025

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Dextromethorphan; deramciclane
• Other Study ID Numbers: EXV802-2-1; 2024-517388-22-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No