Dementia, Frontotemporal
Conditions
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).
Interventions
DRUGVES001
VES001 is an oral, blood brain barrier penetrating ligand of sortilin.
DRUGPlacebo
A matching dosage form, indistinguishable from the active treatment will be used as the placebo treatment.
Sponsors
Vesper Biotechnologies ApS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Part A & B: 1. Healthy men or women aged 18 to 55 years. 2. Body Mass Index between 18 and 32 kg/m2, with a minimum weight of 50 kg. 3. Effective contraception required during the study and for at least 90 days after their last dose. 4. Participants in group 3, where the food effect is being investigated, must be able to eat a high-fat meal within 30 minutes for breakfast.
Exclusion criteria
Part A & B: 1. Medical conditions or treatments that could interfere with the study. 2. History of any known neurologic disease, cognitive impairment, or a history of seizure, (significant) head trauma, or loss of consciousness. 3. History of active malignancy (active cancer cells or tumors) within the last 5 years. 4. Abnormal laboratory test results or infectious diseases (Hepatitis B, Hepatitis C, and/or HIV). 5. Recent medication or supplement use, unless allowed by the investigator. 6. Participation in other research studies involving study treatment or devices. 7. Positive tests for illegal drugs or alcohol at screening. 8. Heavy smoking or inability to abstain from smoking during the study. 9. Excessive consumption of caffeine (more than 8 cups per day). 10. History of severe allergic reactions to medication 11. Recent blood donation or significant blood loss. 12. Pregnancy, breastfeeding, or plans to become pregnant (for women).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs). | Part A: 21 weeks. Part B: 13 weeks. |
| Incidence of clinically significant abnormalities in safety laboratory values. | Part A: 21 weeks. Part B: 13 weeks. |
| Change from baseline in vital sign measurement: Pulse Rate (bpm). | Part A: 21 weeks. Part B: 13 weeks. |
| Change from baseline in vital sign measurement: Systolic blood pressure (mmHg) and Diastolic blood pressure (mmHg). | Part A: 21 weeks. Part B: 13 weeks. |
| Change from baseline in vital sign measurement: Electrocardiogram parameter Heart Rate (HR). | Part A: 21 weeks. Part B: 13 weeks. |
| Change from baseline in vital sign measurement: Electrocardiogram parameter beats per minute (bpm) | Part A: 21 weeks. Part B: 13 weeks. |
| Change from baseline in vital sign measurement: Electrocardiogram parameter PR Interval | Part A: 21 weeks. Part B: 13 weeks. |
| Change from baseline in vital sign measurement: Electrocardiogram parameter QRS Interval | Part A: 21 weeks. Part B: 13 weeks. |
| Change from baseline in vital sign measurement: Electrocardiogram parameter QT Interval. | Part A: 21 weeks. Part B: 13 weeks. |
| Change from baseline in vital sign measurement: Electrocardiogram parameter QTcB (calculated using Bazzet method). | Part A: 21 weeks. Part B: 13 weeks. |
| Change from baseline in vital sign measurement: Electrocardiogram parameter QTcF, (calculated using Fredericia's method). | Part A: 21 weeks. Part B: 13 weeks. |
| Incidence of clinically significant abnormalities in physical/neurological examination findings. | Part A: 21 weeks. Part B: 13 weeks. |
| Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS; Parts B). | Part A: 21 weeks. Part B: 13 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma PK parameter: Area under the concentration-time curve from time zero to infinity (AUCinf). | 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. | Refer to the PK parameters listed above. |
| 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: 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. | — |
| 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. | — |
| 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. | — |
Countries
Netherlands
Outcome results
None listed