Phase 1 SAD/MAD Study of CVN766 in Healthy Volunteers

NCT05105243 | Completed Phase 1 Results

• 1 other identifier: CVN-766
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability, and Pharmacokinetic Study of Escalating Single and Multiple Doses of CVN766 in Healthy participants.

Conditions

Safety Issues; Tolerance

Keywords

PK; Efficacy

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants Reporting at Least One Treatment-emergent Adverse Event (TEAE)

  An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as any AE with onset occurring within 30 days (onset date - last date of dose + 1 ≤30) after study drug administration. Percentage of participants reporting at least one TEAE has been presented.

  Up to Day 14

• Percentage of Participants With Clinically Significant Abnormal Laboratory Parameters

  Blood and urine samples were collected for the analysis of laboratory parameters including clinical chemistry, hematology, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.

  Up to Day 14

• Percentage of Participants With Clinically Significant Changes in 12-Lead Electrocardiogram (ECG) Findings

  12-lead ECG recordings including heart rate and measured PR, QRS, QT, QT interval with Fridericia's correction method (QTcF) and QT interval with Bazett's correction method (QTcB) intervals. 12-lead ECG recordings were obtained after the participants have rested for at least 5 minutes in supine position. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.

  Up to Day 14

• Percentage of Participants With Clinically Significant Abnormal Vital Signs

  Vital signs including blood pressure (systolic and diastolic blood pressure), pulse rate, body temperature, respiratory rate and weight were measured after the participants have rested for at least 5 minutes in supine position. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.

  Up to Day 14

Secondary Outcomes (15)

• Time to Maximum Plasma Concentration (Cmax) (Tmax) After Single Dose Administration of CVN766

  Predose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, 48, and 72 hours postdose at Day 1

• Area Under the Plasma Concentration-time Curve From Time 0 to 24 (AUC24) After Single Dose Administration of CVN766

  Predose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16 and 24 hours postdose at Day 1

• Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC [0-infinity]) After Single Dose Administration of CVN766

  Predose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, 48, and 72 hours postdose at Day 1

• Terminal Elimination Half-life (t1/2z) After Single Dose Administration of CVN766

  Predose (within 15 minutes prior to dosing) and at 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, 48, and 72 hours postdose at Day 1

• Maximum Observed Trough Concentrations After Repeat Dose Administration of CVN766

  At Days 1, 2, 3, 4, 5 and 6

Study Arms (8)

SAD Cohort 1

ACTIVE COMPARATOR

Each dose cohort: 8 participants (6 active:2 placebo). 5 mg.

Drug: CVN766

SAD Cohort 2

ACTIVE COMPARATOR

Each dose cohort: 8 participants (6 active:2 placebo). 15 mg.

Drug: CVN766

SAD Cohort 3

ACTIVE COMPARATOR

Each dose cohort: 8 participants (6 active:2 placebo). 45 mg.

Drug: CVN766

SAD Cohort 4

ACTIVE COMPARATOR

Each dose cohort: 8 participants (6 active:2 placebo). 125 mg.

Drug: CVN766

SAD Cohort 5

PLACEBO COMPARATOR

Each dose cohort: 8 participants (6 active:2 placebo). 250 mg.

Drug: CVN766

MAD Cohort 1

ACTIVE COMPARATOR

Each dose cohort: 8 participants (6 active:2 placebo). 45mg.

Drug: CVN766

MAD Cohort 2

PLACEBO COMPARATOR

Each dose cohort: 8 participants (6 active:2 placebo). 125 mg.

Drug: CVN766

MAD Cohort 3

PLACEBO COMPARATOR

Each dose cohort: 8 participants (6 active:2 placebo). 250 mg.

Drug: CVN766

Interventions

CVN766 DRUG

highly selective orexin-1 receptor (Ox1R) antagonist

MAD Cohort 1; MAD Cohort 2; MAD Cohort 3; SAD Cohort 1; SAD Cohort 2; SAD Cohort 3; SAD Cohort 4; SAD Cohort 5

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participant eligibility is determined according to the following criteria prior to entry into the study:
• In the investigator's opinion, the participant can understand and sign the Informed Consent Form and comply with all protocol requirements.
• The participant is a healthy male or female adult who is 18 to 55 years of age, inclusive at the time of ICF.
• Participant weighs at least 45 kg (99 lbs) and has a BMI between 18.0 and 32.0 kg/m2, inclusive at Screening.
• A male participant who is nonsterilized\* and sexually active with a female partner of childbearing potential\* agrees to use adequate contraception\* from signing the ICF throughout the study and for 12 weeks after the last dose.
• \*Definitions and acceptable methods of contraception are defined in Section 9.1.9 Contraception and Pregnancy Avoidance Procedure, and reporting responsibilities are defined in Section 9.1.10 Pregnancy.
• A female participant of childbearing potential who complies with contraception requirements\* or a female with no childbearing potential, defined as the participant 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).

You may not qualify if:

• Participant has received any investigational compound within 30 days prior to the first dose of study medication or within 5 half-lives, whichever is greater.
• Participant is a study site employee or an immediate family member of a study site employee.
• Participant has evidence of CS neurologic, cardiovascular, pulmonary, hepatic, hematopoietic disease, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, serious allergy, full-body allergic skin rash (including hives), psychiatric disorder, or other abnormality that may impact the ability of the participant to participate or potentially confound the study results.
• There is any finding in the participant's medical history, physical examination, or safety laboratory tests giving reasonable suspicion of a disease that would contraindicate taking CVN766 or a similar drug in the same class or that might interfere with the conduct of the study.
• Participant has a known hypersensitivity to any component of the formulation of CVN766.
• Participant has a positive urine result for drugs of abuse at Screening or Inpatient Check-in (Day -1).
• Participant has a history of drug abuse or a history of alcohol abuse (more than 14 units/week) within 1 year prior to the Screening Visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.
• Participant has taken any excluded medication, supplements, or food products listed in the Excluded Medications and Dietary Products table as listed in Table 3: Excluded Medications and Dietary Products.
• Male participants who do not agree to all the following rules: when sexually active with a female partner(s) of childbearing potential during the study, and for 12 weeks after the last dose of study drug: a) must use an acceptable method of birth control (condom or surgical sterilization) and b) refrain from sexual activity with female partners who do not use an acceptable method of birth control. Barrier contraception (condom) must be used by all-male participants who were not surgically sterilized at least 90 days prior to screening. Male participants must also agree to refrain from sperm donation during the study and until 12 weeks after the last dose of study drug.
• Female participants who are pregnant or breastfeeding or plan to become pregnant or donate ova during the study or 30 days after the last dose of the study drug. Women of childbearing potential must agree to practice an acceptable method of birth control (e.g., oral or parenteral contraceptives, intrauterine device, barrier, abstinence).
• \*Definitions and acceptable methods of contraception are defined in Section 9.1.9, Contraception and Pregnancy Avoidance Procedure, and reporting responsibilities are defined in Section 9.1.10, Pregnancy.
• Participant has previously had a seizure or convulsion (lifetime, with the exception of febrile seizures), including absence seizure.
• Participant has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (i.e., a history of malabsorption, any surgical intervention known to impact absorption \[e.g., bariatric surgery or bowel resection\], esophageal reflux, peptic ulcer disease, erosive esophagitis, or frequent \[i.e., more than once per week\] occurrence of heartburn).
• Participant has a history of cancer or other malignancy, except for basal cell carcinoma or squamous cell carcinoma that has been in remission for at least 3 years prior to Day 1.
• Participant has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or a human immunodeficiency virus infection at Screening.

Sponsors & Collaborators

• Cerevance: lead

Study Sites (1)

Nucleus Network

Melbourne, Victoria, 3004, Australia

Location

Results Point of Contact

• Title: Michelle Charles, Executive Director Regulatory Affairs
• Organization: Cerevance

Michelle.Charles@cerevance.com

(408) 220-5722

Study Officials

• Ottavio Vitolo, MD

  Cerevance

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind. placebo-controlled.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: For the single-dose regimen, approximately 40 healthy male or female participants will be enrolled in 1 of 5 single-dose cohorts (designated as S1 through S5, respectively) in an ascending fashion. Each cohort will consist of 8 participants randomized to CVN766 or placebo, whereby 6 participants will receive a single oral dose of CVN766 suspension, and 2 participants will receive a matching placebo suspension under overnight fasted conditions. For the multiple-dose regimen, approximately 24 healthy male and female participants 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. The dose levels planned to be studied in the multiple-dose regimen are 45, 125, and 250 mg CVN766 for multiple-dose cohorts M1 through M3, respectively.

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: November 3, 2021
• Study Start: January 17, 2022
• Primary Completion: October 30, 2022
• Study Completion: November 21, 2022
• Last Updated: November 4, 2024
• Results First Posted: November 4, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)