A Randomised, Double-blind, Placebo-controlled Single and Multiple Ascending Dose Study in Healthy Volunteers and Asymptomatic GRN Mutation Carriers to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VES001
Overview
- Phase
- Phase 1
- Intervention
- VES001
- Conditions
- Dementia, Frontotemporal
- Sponsor
- Vesper Biotechnologies ApS
- Enrollment
- 78
- Locations
- 1
- Primary Endpoint
- Change from baseline in vital sign measurement: Systolic blood pressure (mmHg) and Diastolic blood pressure (mmHg).
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 1, randomized, placebo-controlled, double-blind study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses of VES001 in a two part followed by a multicenter, open-label Phase 1b study in asymptomatic GRN mutation carriers.
Part A will evaluate the safety, tolerability, PK, and PD of single doses of VES001 in healthy volunteers.
Part B will evaluate the safety, tolerability, PK, and PD of multiple doses of VES001 in healthy volunteers.
Detailed Description
Part A will include six cohorts, with eight participants per cohort. Participants in each cohort will be randomised in a 6:2 ratio (VES001 vs. placebo). Part B will include three cohorts, with ten participants per cohort. Participants in each cohort will be randomised in a 8:2 ratio (VES001 vs. placebo).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
VES001 (Healthy Participants)
Part A: Ascending single doses and Part B: Multiple ascending dose (seven days of treatment), for healthy volunteers.
Intervention: VES001
Placebo (Healthy Participants)
Part A: Ascending single doses and Part B: Multiple ascending dose (seven days of treatment), for healthy volunteers.
Intervention: Placebo
Outcomes
Primary Outcomes
Change from baseline in vital sign measurement: Systolic blood pressure (mmHg) and Diastolic blood pressure (mmHg).
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Incidence of clinically significant abnormalities in safety laboratory values.
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Pulse Rate (bpm).
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter Heart Rate (HR).
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter beats per minute (bpm)
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter PR Interval
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs).
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter QRS Interval
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter QT Interval.
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter QTcB (calculated using Bazzet method).
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS; Parts B).
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter QTcF, (calculated using Fredericia's method).
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Incidence of clinically significant abnormalities in physical/neurological examination findings.
Time Frame: Part A: 21 weeks. Part B: 13 weeks.
Secondary Outcomes
- Plasma PK parameter: Area under the concentration-time curve from time zero to infinity AUCinf(%extrapolated).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Area under the concentration-time from time zero to time of last measurable concentration (AUClast).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Area under the concentration-time curve from time zero to infinity (AUCinf).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Apparent total clearance following extravascular administration (CL/F).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Maximum concentration (Cmax).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Absorption lag time (tlag).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Time to reach maximum concentration (tmax).(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Terminal elimination half-life (t1/2).(Part A: 21 weeks. Part B: 13 weeks.)
- Concentration of VES001 in plasma/CSF ratio in the highest two dose level cohorts in Part A.(Part A: 21 weeks. Part B: 13 weeks.)
- Concentration of VES001 in plasma/CSF ratio in all dose level cohorts in Part B.(Part A: 21 weeks. Part B: 13 weeks.)
- Comparison of the plasma PK of VES001 following a single oral dose in the fed and fasted state in Part A.(Part A: 21 weeks. Part B: 13 weeks.)
- Plasma PK parameter: Apparent volume of distribution during the terminal elimination phase after extravascular administration (Vz/F).(Part A: 21 weeks. Part B: 13 weeks.)
- Concentration of VES001 in CSF in the highest two dose level cohorts in Part A.(Part A: 21 weeks. Part B: 13 weeks.)
- Concentration of VES001 in CSF in all dose level cohorts in Part B.(Part A: 21 weeks. Part B: 13 weeks.)