Safety, Tolerability, and Dose Response of VNA-318 in Healthy Males

NCT06721091 | Completed Phase 1 DMC

• 1 other identifier: VNA-318-01
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, randomized, double-blind, placebo-controlled study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses (SAD) and multiple ascending doses (MAD) of VNA-318 in healthy male subjects.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (10)

• Safety and tolerability of single dose

  • Percentage of subjects who experienced at least one treatment-emergent adverse event (TEAE) by seriousness, intensity, and relatedness from baseline through follow-up,

  From Day 1 to Day 7

• Safety and tolerability of single dose

  • Percentage of subjects who discontinued due to a TEAE,

  From Day 1 to Day 7

• Safety and tolerability of single dose

  • Percentage of subjects who met the abnormal criteria for safety laboratory tests at least once post-dose,

  From Day 1 to Day 7

• Safety and tolerability of single dose

  • Percentage of subjects who met the abnormal criteria for vital signs (blood pressure, pulse rate, and body temperature) measurement at least once post-dose,

  From Day 1 to Day 7

• Safety and tolerability of single dose

  • Percentage of subjects who meet the abnormal criteria for safety electrocardiogram (ECG) parameters at least once post-dose.

  From Day 1 to Day 7

• Safety and tolerability of multiple dose

  • Percentage of subjects who experienced at least one treatment-emergent adverse event (TEAE) by seriousness, intensity, and relatedness from baseline through follow-up,

  From Day 1 to Day 19

• Safety and tolerability of multiple dose

  • Percentage of subjects who discontinued due to a TEAE,

  From Day 1 to Day 19

• Safety and tolerability of multiple dose

  • Percentage of subjects who met the abnormal criteria for safety laboratory tests at least once post-dose,

  From Day 1 to Day 19

• Safety and tolerability of multiple dose

  • Percentage of subjects who met the abnormal criteria for vital signs (blood pressure, pulse rate, and body temperature) measurement at least once post-dose,

  From Day 1 to Day 19

• Safety and tolerability of multiple dose

  • Percentage of subjects who meet the abnormal criteria for safety electrocardiogram (ECG) parameters at least once post-dose.

  From Day 1 to Day 19

Secondary Outcomes (21)

• SAD - Cmax

  Day 1

• SAD tmax

  Day 1

• SAD Clast

  Day 1

• SAD Tlast

  Day 1

• SAD AUC0-inf

  Day 1

Study Arms (4)

Part 1 (SAD): Active

EXPERIMENTAL

Single oral dose of VNA-318

Drug: VNA-318

Part 1 (SAD): Placebo

PLACEBO COMPARATOR

Single oral dose of Matching Placebo

Drug: Placebo

Part 2 (MAD): Active

EXPERIMENTAL

Multiple oral doses of VNA-318

Drug: VNA-318

Part 2 (MAD): Placebo

PLACEBO COMPARATOR

Multiple oral doses of Matching Placebo

Drug: Placebo

Interventions

VNA-318 DRUG

Part 1 will consist of administration of VNA-318 at the doses of 5 mg to 180 mg in 5 to 8 successive cohorts. Part 2 will consist of administration of VNA-318 in 3 to 4 successive cohorts. The doses will be selected based on safety and tolerability assessments, as well as PK and, if applicable, PD data from SAD. Once PK suggests that the therapeutic dose has been reached in the SAD part, the SAD and MAD parts of the study could be run in parallel.

Part 1 (SAD): Active; Part 2 (MAD): Active

Placebo DRUG

Part 1 (SAD) will consist of administration of matching placebo at the doses of 5 mg to 180 mg in 5 to 8 successive cohorts. Part 2 (MAD) will consist of administration of matching placebo in 3 to 4 successive cohorts. The doses will be selected based on safety and tolerability assessments, as well as PK and, if applicable, PD data from SAD.

Part 1 (SAD): Placebo; Part 2 (MAD): Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Gender Eligibility Details: Mâle
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects able and willing to provide written informed consent prior any other clinical study procedures.
• Subjects able and willing to comply with the clinical study protocol (hospitalization periods, scheduled visits, IMP administration, clinical laboratory tests, and other study procedures including lifestyle considerations) according to International Council of Harmonization (ICH) and local regulations.
• Demography
• Healthy male.
• Aged 18-65 years (inclusive) on the day of signing the informed consent form (ICF). - Aged 18-45 years (inclusive) for the SAD optional exploratory cohort with CSF sampling
• Have a body mass index (BMI) between 18.5-30.0 kg/m2 (inclusive) at screening and D 1.
• Health Status
• Have normal physical examination and vital signs (VS) results within normal ranges at screening and D˗1. If outside normal ranges, it must be considered by the Investigator without clinically significant abnormal findings.
• Have a clinical laboratory of blood and urine within normal ranges at screening and D-1. If outside normal ranges, it must be considered by the Investigator without clinically significant abnormal findings.
• Have 12-lead ECG results without clinically significant abnormal findings confirmed by the Investigator at screening and D-1.
• Non-smoker (and no other nicotine use) as determined by history (no nicotine use over the past 6 months) and by urine cotinine concentration (\< 200 ng/mL) at screening and D-1.
• Contraception
• If sexually active and not sterile, with a woman of childbearing potential, the subject and his partner must commit to using a highly effective method of birth control starting at screening and throughout the entire study and for 90 days after last dose of IMP administration:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, started at least 4 weeks prior to the dosing (D1) and use of condom for the male partner.
• Progestogen-only hormonal contraception associated with inhibition of ovulation, started at least 4 weeks prior to the dosing (D1) and use of condom for the male partner.

You may not qualify if:

• Medical History
• Any condition or disease detected during the medical interview/physical examination that could relapse during or immediately after the study, or would render the subject unsuitable for the study, place the subject at undue risk, or interfere with the ability of the subject to complete the clinical study, as determined by the Investigator.
• Have a history of and/or current clinically significant disease/disorder determined by the Investigator: gastrointestinal, endocrine, renal, hepatic, immunological, cardiovascular, hematological, respiratory, neurologic, metabolic, urologic, dermatologic, psychiatric disorder, or allergic disease, hypersensitivity, or allergic reactions excluding mild asymptomatic seasonal allergies (either spontaneous or following drug administration), or malignancy (including lymphoma, leukemia, and skin cancer) unless remission over 10 years.
• Have a personal or family history of prolonged QT interval syndrome or Torsade de Pointes, or family history of sudden death.
• Have current presence of an illness, such as a common cold, isolated headache, diarrhea, etc., within 14 days prior to D1 that is categorized as clinically significant by the Investigator.
• History or presence of regular use of recreational or illicit drugs within 1 year before study D1.
• Donation of blood or blood loss (i.e., \> 450 ml) within 90 days, or donated plasma within 7 days prior to D-1.
• Known significant hypersensitivity or other contraindication to any of the components of the study drug.
• History of suicidal behavior or any risk of suicidal behavior in the opinion of a certified clinician or as evidenced by a "yes" to any questions of Columbia-Suicide Severity Rating Scale (C-SSRS) taken at screening (MAD part only).
• Confirmed coronavirus disease 2019 (COVID-19) infection within 90 days of screening or contact with an individual with COVID-19 infection in the past 14 days at D-1.
• Physical and Laboratory Findings
• Have a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or human immunodeficiency virus 1 and/or 2 antibodies (anti-HIV1 and anti HIV2 Ab) at screening.
• Positive findings of urine drug screen (methadone, barbiturates, morphine, amphetamines, methamphetamines, opiates (including morphine), cannabinoids, cocaine, benzodiazepines, tricyclic antidepressants (TCA), 3,4-methylenedioxy-methamphetamine \[MDMA; ecstasy\]).
• Have a positive alcohol breath test result at screening or D-1.
• Lifestyle restrictions

Sponsors & Collaborators

• Biotrial: collaborator
• VANDRIA: lead

Study Sites (1)

Biotrial

Rennes, 35000, France

Location

Study Officials

• Klaus Dugi, MD

  Vandria SA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2024
• First Posted: December 6, 2024
• Study Start: December 3, 2024
• Primary Completion: November 27, 2025
• Study Completion: November 27, 2025
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)