A Single and Multiple Ascending Dose Trial of CVL-354 in Healthy Participants

Study Overview
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Brief Summary
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This is a 2-part, double-blind, randomized, placebo-controlled, first-in-human trial evaluating a single ascending dose (4-way crossover, Part A) and multiple ascending doses (Part B) of CVL-354.

Official Title
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A Phase 1, Double-blind (Investigator and Participant), First-in-Human Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of CVL-354 in Healthy Participants

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: Drug: CVL-354
* Drug: Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women of nonchildbearing potential and men 18 to 55 years, inclusive. Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, ECG, vital sign measurements, and laboratory test results, as evaluated by the investigator. Body mass index of 18.5 to 30.0 kg/m2, inclusive, and total body weight >50 kg (110 lb) at Screening. A male participant with a pregnant or a nonpregnant partner of childbearing potential must agree to use contraception during the trial and 14 days following the last dose of study drug. Capable of giving signed informed consent Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements. Exclusion Criteria: Current or past history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine, hematological, immunological, or neurological, or psychiatric disease that, in the opinion of the investigator or medical monitor, could compromise either participant safety or the results of the trial. Serious risk of suicide in the opinion of the Investigator History of substance or alcohol-use disorder (excluding nicotine or caffeine) within 12 months prior to signing the ICF. Any condition that could possibly affect drug absorption Receipt of SARS-CoV2 vaccination or booster as follows: mRNA: within 14 days prior to dosing Non-mRNA: within 28 days prior to dosing In addition, participants who plan to receive SARS-CoV2 vaccination or booster while participating in the trial or for at least 14 days after the last dose of IMP will be excluded. Have recently been diagnosed with symptomatic COVID-19 or test positive for COVID-19 within 30 days prior to signing the ICF. Use of prohibited medication prior to randomization or likely to require prohibited concomitant therapy (eg, prescription and over-the-counter medications, herbal medications, vitamins, and supplements) during the trial Either of the following: History of HIV, hepatitis B, or hepatitis C infection Positive result for HIV antibody, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody Positive drug screen (including nicotine) or a positive test for alcohol Abnormal clinical laboratory test results or vital measurements at Screening and Check-in Estimated glomerular filtration rate at Screening <90 mL/min/1.73 m2, as calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation Abnormal 12-lead ECG at Screening or initial Check-In (Day -1). Known allergy or hypersensitivity to the IMP, closely related compounds, or any of their specified ingredients. Current enrollment or past participation within 30 days or 5 half-lives (whichever is longer) prior to signing the ICF in any other clinical trial involving an IMP. Any other abnormal safety findings unless, based on the investigator's judgment, the findings are not medically significant and would not impact the safety of the participant or the interpretation of the trial results.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part A of the trial is a double-blind, randomized, placebo-controlled 4-period, 4-sequence, crossover design to evaluate the PK, safety, and tolerability of single doses of CVL-354 in healthy participants. Except for a potential food effect period, all treatments will be administered under fasted conditions. Part B of the trial is a double-blind, randomized, placebo-controlled trial to evaluate PK, safety, and tolerability of CVL-354 in multiple ascending doses.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Ascending Dose (SAD) Cohorts 1-3<br>In Cohorts 1 and 2, all participants will receive treatment with up to 3 single oral doses of CVL-354 and/or 1 single oral dose of placebo in a 4-period crossover design. The starting dose of CVL-354 will be 0.5 mg. Participants will be randomized to 1 of 4 treatment sequences. Cohort 3 may be used to evaluate additional doses or evaluate food effect, depending on the results from Cohorts 1 and 2. | Drug: Drug: CVL-354<br>* Oral solution/suspension<br>Drug: Drug: Placebo<br>* Oral solution/suspension<br>|
| Experimental: Multiple Ascending Dose (MAD) Cohorts 1-5<br>All participants will receive treatment with multiple oral doses of CVL-354 (dose and regimen to be determined) or matching placebo for 14 days. | Drug: Drug: CVL-354<br>* Oral solution/suspension<br>Drug: Drug: Placebo<br>* Oral solution/suspension<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Part A&B: 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 will be counted as treatment-emergent AE (TEAE). | Up to 29 days following last dose with IMP | 
| Primary Part A&B: Incidence of clinically significant changes in electrocardiogram (ECG) results |  | Up to 17 days following last dose with IMP | 
| Primary Part A&B: Incidence of 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. | Up to 17 days following last dose with IMP | 
| Primary Part A&B: Incidence of clinically significant changes in clinical laboratory results |  | Up to 17 days following last dose with IMP | 
| Primary Part A&B: Incidence of clinically significant changes in physical and neurological examination results |  | Up to 17 days following last dose with IMP | 
| Primary Part A&B: Changes in suicidality assessed using the Columbia Suicide-Severity Rating Scale (C-SSRS) | The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe). Greater lethality or potential lethality of suicidal behaviors (endorsed on the Behavior subscale) indicates increased risk. | Up to 17 days following last dose with IMP | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depressive Disorder, Healthy Volunteer, Mental Disorders