Study of CVN424 in Healthy Subjects

Study Overview
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Brief Summary
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This is a phase 1, randomized, double-blind, placebo-controlled, single- and multiple-dose ascending study in healthy subjects.

Detailed Description
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Part 1: Single-Dose Regimen and Fasted-Fed Crossover - For the single-dose regimen, approximately 40 healthy male and female subjects will be enrolled in 1 of 5 single dose cohorts (designated as S1 through S5, respectively) in an ascending fashion. Part 2: Multiple-Dose Regimen - For the multiple-dose regimen, approximately 24 healthy male and female subjects age 18 to 50 years old will be enrolled in 1 of the 3 multiple-dose cohorts (designated as M1 through M3, respectively) in an ascending fashion.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Doses of CVN424 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: CVN424
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In the opinion of the Investigator, the subject is capable of understanding and complying with protocol requirements. The subject signs and dates a written informed consent form (ICF) and any required privacy authorization prior to the initiation of any study procedures. Subject is a healthy male or female adult who is 18 to 50 years of age inclusive at the time of ICF and study drug dosing. Subject weighs at least 45 kg (99 lbs) and has a BMI between 18.0 and 30.0 kg/m2, inclusive at Screening. A male subject who is nonsterilized and sexually active with a female partner of childbearing potential* agrees to use adequate contraception* from signing of the ICF throughout the duration of the study and for 12 weeks after last dose. A female subject with no childbearing potential, defined as the subject has been surgically sterilized (hysterectomy, bilateral oophorectomy or tubal ligation) or who are postmenopausal (defined as continuous amenorrhea of at least 2 years and FSH>40 IU/L). Exclusion Criteria: Subjects have a known hypersensitivity to any component of the formulation of CVN424. Subjects have evidence of CS neurologic, cardiovascular, pulmonary, hepatic, hematopoietic disease, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, serious allergy, allergic skin rash, psychiatric disorder, or other abnormality that may impact the ability of the subject to participate or potentially confound the study results. There is any finding in the subject's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a condition that might interfere with the conduct or interpretation of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Single ascending dose and multiple ascending dose study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Single Ascending Dose<br>The planned dose levels will be 1, 5, 25, 75, and 225 mg CVN424 and matching placebo. | Drug: CVN424<br>* SAD / MAD<br>Drug: Placebo<br>* Placebo<br>|
| Active Comparator: Multiple Ascending Dose<br>The planned dose levels will be 25, 75, and 150 mg CVN424 and matching placebo. | Drug: CVN424<br>* SAD / MAD<br>Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of adverse events | Occurrence of all adverse events from signing of informed consent through end of study treatment. | Baseline through 14 days post-dose | 
| Evaluation of Hematology | RBC | Baseline through 14 days post-dose | 
| Evaluation of Vital Signs | Oral Temperature (°C ) | Baseline through 14 days post-dose | 
| Evaluation of Electrocardiograms | Standard 12-lead ECG - QT interval | Baseline through 14 days post-dose | 
| Evaluation of BMI | Weight and Height will be combined to calculate BMI using the following formula: BMI = weight (kg)/[height (m)]2 | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | ALT | Baseline through 14 days post-dose | 
| Evaluation of Urinalysis | pH | Baseline through 14 days post-dose | 
| Evaluation of Vital Signs | Respiration rate | Baseline through 14 days post-dose | 
| Evaluation of Vital Signs | Pulse rate | Baseline through 14 days post-dose | 
| Evaluation of Vital Signs | Blood pressure (both systolic and diastolic) | Baseline through 14 days post-dose | 
| Evaluation of Hematology | WBC with differential (%and absolute) platelets, PT/INR | Baseline through 14 days post-dose | 
| Evaluation of Hematology | Hemoglobin | Baseline through 14 days post-dose | 
| Evaluation of Hematology | Hematocrit | Baseline through 14 days post-dose | 
| Evaluation of Hematology | PT/INR | Baseline through 14 days post-dose | 
| Evaluation of Hematology | Platelets | Baseline through 14 days post-dose | 
| Evaluation of Electrocardiograms | Standard 12-lead ECG- QTcB interval | Baseline through 14 days post-dose | 
| Evaluation of Electrocardiograms | Standard 12-lead ECG - QTcF interval | Baseline through 14 days post-dose | 
| Evaluation of Electrocardiograms | Standard 12-lead ECG - RR interval | Baseline through 14 days post-dose | 
| Evaluation of Electrocardiograms | Standard 12-lead ECG - QRS interval | Baseline through 14 days post-dose | 
| Evaluation of Electrocardiograms | Standard 12-lead ECG - PR interval | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Albumin | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Alkaline phosphatase | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Lipase | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | AST | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Total bilirubin | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Direct bilirubin | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Total protein | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Creatinine | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Blood urea nitrogen | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Creatine kinase Glucose, Chloride, Bicarbonate | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | GGT | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Potassium | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Sodium | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Glucose | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Chloride | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Bicarbonate | Baseline through 14 days post-dose | 
| Evaluation of Serum Chemistry | Calcium | Baseline through 14 days post-dose | 
| Evaluation of Urinalysis | Specific gravity | Baseline through 14 days post-dose | 
| Evaluation of Urinalysis | Protein | Baseline through 14 days post-dose | 
| Evaluation of Urinalysis | Glucose | Baseline through 14 days post-dose | 
| Evaluation of Urinalysis | Blood | Baseline through 14 days post-dose | 
| Evaluation of Urinalysis | Nitrite | Baseline through 14 days post-dose | 
| Evaluation of Urinalysis | Microscopic Analysis (only if positive dipstick results): RBC/high power field, WBC/high power field, Epithelial cells, casts | Baseline through 14 days post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration (AUC) of CVN424 | To evaluate the pharmacokinetics of single and multiple doses of CVN424. Pharmacokinetic parameters including, but not limited to area under the plasma concentration-time curve (AUC) from 0 to 24hours (AUC0-24) | SAD: PK Collection on Day 1-4, and early termination (up to 8 days); MAD: PK Collection on Day 1-10, and early termination (up to 14 days) | 
| Plasma Concentration (Cmax) of CVN424 | To evaluate the pharmacokinetics of single and multiple doses of CVN424. Pharmacokinetic parameters including, but not limited to maximum plasma concentration (Cmax). | SAD: PK Collection on Day 1-4, and early termination (up to 8 days); MAD: PK Collection on Day 1-10, and early termination (up to 14 days) | 
| Food effect by measurement of plasma PK (Cmax) | Assess the effect of food on the bioavailability in the current formulation after digesting a high caloric meal. | Baseline through 14 days post-dose | 
| Food effect by measurement of plasma PK (AUC) | Assess the effect of food on the bioavailability in the current formulation after digesting a high caloric meal. | Baseline through 14 days post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteers