A Trial of the Safety, Tolerability, and Pharmacodynamics of CVL-871 in Subjects With Dementia-Related Apathy

Study Overview
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Brief Summary
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The purpose of this study is to determine whether CVL-871 is safe and tolerable in patients with Dementia-Related Apathy and if CVL-871 shows changes in clinical measurements of apathy.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Trial To Evaluate the Safety, Tolerability, and Pharmacodynamics of CVL-871 in Subjects With Dementia-Related Apathy

Conditions
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Apathy in Dementia

Intervention / Treatment
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* Drug: CVL-871 1.0 mg
* Drug: CVL-871 3.0 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets diagnostic criteria for apathy in neurocognitive disorders Clinically significant apathy Mild to Moderate Dementia (AD, FTD, VAD, or DLB) Exclusion Criteria: Other significant psychiatric disorder(s) Other neurological disorders (other than AD, FTD, VAD, or DLB)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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
Interventional Model Description: Participants are assigned to one of two or more groups in parallel for the duration of the study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CVL-871 1.0 mg<br>Participants will receive CVL-871 tablets orally QD up to the maximum dose of 1.0 milligrams (mg) until Day 85 during the treatment period. | Drug: CVL-871 1.0 mg<br>* CVL-871 1.0 mg, oral (tablet), once per day for 12 weeks (stepped up-titration of dose days 1-7)<br>|
| Experimental: CVL-871 3.0 mg<br>Participants will receive CVL-871 tablets orally QD up to the maximum dose of 3.0 milligrams (mg) until Day 85 during the treatment period. | Drug: CVL-871 3.0 mg<br>* CVL-871 3.0 mg QD oral (tablet), once per day for 12 weeks (stepped up-titration of dose days 1-21)<br>|
| Placebo Comparator: Placebo<br>Participants will receive a placebo matched to CVL-871 tablets orally QD until Day 85 during the treatment period. | Drug: Placebo<br>* Placebo QD, oral (tablet), once per day for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Treatment Emergent Adverse Events (TEAEs) | Any AE occurring following the start of treatment or occurring before treatment but increasing in severity afterward were counted as treatment-emergent AE (TEAE) | From first dose of study drug up to Week 16 (follow-up period) | 
| Incidence of clinically significant changes in electrocardiogram (ECG) results | Assessment of clinically significant changes in QT intervals measured by 12-lead ECG recording after the participant has been supine and at rest for at least 5 minutes | Baseline up to Week 16 or early termination (ET) | 
| Incidence of clinically significant changes in clinical laboratory results |  | Baseline up to Week 14 or early termination (ET) | 
| Incidence in clinically significant changes in vital sign measurements | Assessment of clinically significant changes in vital signs including temperature, systolic and diastolic blood pressure, and heart rate. | Baseline up to Week 14 or early termination (ET) | 
| Incidence of clinically significant changes in physical and neurological examination results |  | Screening up to Week 16 or early termination (ET) | 
| Clinically significant findings in suicidality assessed using the Columbia Suicide-Severity Rating Scale (C-SSRS) | The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from wish to be dead to active suicidal ideation with specific plan and intent. The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent). | Baseline up to Week 14 (follow up period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the Dementia Apathy Interview and Rating (DAIR) score | The Dementia Apathy Interview Rating (DAIR) is a 16-item structured interview with the primary caregiver designed to assess illness-related changes in motivation, emotional responsiveness, and engagement. The total apathy score is a sum of all items reflecting change (items for which there is no change are not rated), divided by the number of items completed, with higher scores representing greater average apathy. In addition, the frequency of these behaviors is assessed; higher scores represent more frequent apathy-related behavior. | Baseline up to Week 12 or early termination (ET) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dementia, Apathy