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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VES001 (Healthy Participants) | Experimental | Part A: Ascending single doses and Part B: Multiple ascending dose (seven days of treatment), for healthy volunteers. |
|
| Placebo (Healthy Participants) | Placebo Comparator | Part A: Ascending single doses and Part B: Multiple ascending dose (seven days of treatment), for healthy volunteers. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VES001 | Drug | VES001 is an oral, blood brain barrier penetrating ligand of sortilin. |
|
| Measure | Description | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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: Area under the concentration-time curve from time zero to infinity AUCinf(%extrapolated). | Part A: 21 weeks. Part B: 13 weeks. |
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Inclusion Criteria Part A & B:
Exclusion Criteria Part A & B:
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| Name | Affiliation | Role |
|---|---|---|
| Mads Kjolby, MD, PhD | Vesper Bio | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Human Drug Research | Leiden | 2333 | Netherlands |
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| ID | Term |
|---|---|
| D057180 | Frontotemporal Dementia |
| ID | Term |
|---|---|
| D057174 | Frontotemporal Lobar Degeneration |
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| Placebo | Drug | A matching dosage form, indistinguishable from the active treatment will be used as the placebo treatment. |
|
| 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. |
| 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. |
| Comparison of the plasma PK of VES001 following a single oral dose in the fed and fasted state in Part A. | Refer to the PK parameters listed above. | Part A: 21 weeks. Part B: 13 weeks. |
| D009422 | Nervous System Diseases |
| D057177 | TDP-43 Proteinopathies |
| D019636 | Neurodegenerative Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |