Study of CVN424 in Healthy Subjects (CVN424)

• ClinicalTrials.gov Identifier: NCT03657030
• Recruitment Status: Completed
• First Posted: September 4, 2018
• Last Update Posted: July 23, 2019
• Sponsor: Cerevance Beta, Inc.
• Information provided by (Responsible Party): CerevanceBeta ( Cerevance Beta, Inc. )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: CVN424; Drug: Placebo	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Single ascending dose and multiple ascending dose study
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Doses of CVN424 in Healthy Subjects
• Actual Study Start Date: September 18, 2018
• Actual Primary Completion Date: March 1, 2019
• Actual Study Completion Date: May 30, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Single Ascending Dose; The planned dose levels will be 1, 5, 25, 75, and 225 mg CVN424 and matching placebo.	Drug: CVN424; SAD / MAD; Drug: Placebo; Placebo
Active Comparator: Multiple Ascending Dose; The planned dose levels will be 25, 75, and 150 mg CVN424 and matching placebo.	Drug: CVN424; SAD / MAD; Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures :

1. Evaluation of adverse events [ Time Frame: Baseline through 14 days post-dose ]
   Occurrence of all adverse events from signing of informed consent through end of study treatment.
2. Evaluation of Hematology [ Time Frame: Baseline through 14 days post-dose ]
   RBC
3. Evaluation of Vital Signs [ Time Frame: Baseline through 14 days post-dose ]
   Oral Temperature (°C )
4. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post-dose ]
   Standard 12-lead ECG - QT interval
5. Evaluation of BMI [ Time Frame: Baseline through 14 days post-dose ]
   Weight and Height will be combined to calculate BMI using the following formula: BMI = weight (kg)/[height (m)]2
6. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
   ALT
7. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post-dose ]
   pH
8. Evaluation of Vital Signs [ Time Frame: Baseline through 14 days post-dose ]
   Respiration rate
9. Evaluation of Vital Signs [ Time Frame: Baseline through 14 days post-dose ]
   Pulse rate
10. Evaluation of Vital Signs [ Time Frame: Baseline through 14 days post-dose ]
    Blood pressure (both systolic and diastolic)
11. Evaluation of Hematology [ Time Frame: Baseline through 14 days post-dose ]
    WBC with differential (%and absolute) platelets, PT/INR
12. Evaluation of Hematology [ Time Frame: Baseline through 14 days post-dose ]
    Hemoglobin
13. Evaluation of Hematology [ Time Frame: Baseline through 14 days post-dose ]
    Hematocrit
14. Evaluation of Hematology [ Time Frame: Baseline through 14 days post-dose ]
    PT/INR
15. Evaluation of Hematology [ Time Frame: Baseline through 14 days post-dose ]
    Platelets
16. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post-dose ]
    Standard 12-lead ECG- QTcB interval
17. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post-dose ]
    Standard 12-lead ECG - QTcF interval
18. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post-dose ]
    Standard 12-lead ECG - RR interval
19. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post-dose ]
    Standard 12-lead ECG - QRS interval
20. Evaluation of Electrocardiograms [ Time Frame: Baseline through 14 days post-dose ]
    Standard 12-lead ECG - PR interval
21. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Albumin
22. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Alkaline phosphatase
23. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Lipase
24. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    AST
25. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Total bilirubin
26. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Direct bilirubin
27. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Total protein
28. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Creatinine
29. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Blood urea nitrogen
30. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Creatine kinase Glucose, Chloride, Bicarbonate
31. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    GGT
32. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Potassium
33. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Sodium
34. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Glucose
35. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Chloride
36. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Bicarbonate
37. Evaluation of Serum Chemistry [ Time Frame: Baseline through 14 days post-dose ]
    Calcium
38. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post-dose ]
    Specific gravity
39. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post-dose ]
    Protein
40. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post-dose ]
    Glucose
41. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post-dose ]
    Blood
42. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post-dose ]
    Nitrite
43. Evaluation of Urinalysis [ Time Frame: Baseline through 14 days post-dose ]
    Microscopic Analysis (only if positive dipstick results): RBC/high power field, WBC/high power field, Epithelial cells, casts

Secondary Outcome Measures :

1. Plasma Concentration (AUC) of CVN424 [ Time Frame: 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) ]
   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)
2. Plasma Concentration (Cmax) of CVN424 [ Time Frame: 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) ]
   To evaluate the pharmacokinetics of single and multiple doses of CVN424. Pharmacokinetic parameters including, but not limited to maximum plasma concentration (Cmax).
3. Food effect by measurement of plasma PK (Cmax) [ Time Frame: Baseline through 14 days post-dose ]
   Assess the effect of food on the bioavailability in the current formulation after digesting a high caloric meal.
4. Food effect by measurement of plasma PK (AUC) [ Time Frame: Baseline through 14 days post-dose ]
   Assess the effect of food on the bioavailability in the current formulation after digesting a high caloric meal.

Other Outcome Measures:

1. DNA isolation and genotyping [ Time Frame: Day 1 ]

   Drug metabolic enzyme and transporter polymorphisms that may contribute to variability in CVN424 will be reported.

   Single-dose -pre-dose

   Multi-dose

   -pre-dose

2. RNA isolation and genotyping [ Time Frame: Day 1 and Day 7 ]

   Single-dose -pre-dose, 8 and 24 hours post dose

   Multi-dose

   -pre-dose, 8 and 24 hours post dose

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Texas

PPD Development, LP

Austin, Texas, United States, 78744

Sponsors and Collaborators

Cerevance Beta, Inc.

Investigators

• Study Director: David H Margolin, MD, PhD; Cerevance, Inc.

More Information

• Responsible Party: Cerevance Beta, Inc.
• ClinicalTrials.gov Identifier: NCT03657030
• Other Study ID Numbers: CVN424-101
• First Posted: September 4, 2018
• Last Update Posted: July 23, 2019
• Last Verified: July 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by CerevanceBeta ( Cerevance Beta, Inc. ):

Healthy Volunteers