A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VES001 in Healthy Participants (SORT-IN-1)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Dementia, Frontotemporal
• Intervention / Treatment: Drug: VES001; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mads Kjoelby, MD, PhD.; Phone Number: +45 60866653; Email: mfk@vesperbio.com
• Study Contact Backup: Name: Simone Prichander; Email: sp@vesperbio.com

Study Locations

• Netherlands
  • Leiden, Netherlands, 2333
    • Recruiting
    • Center for Human Drug Research
    • Contact: CHDR Recruitment; Phone Number: +31 71 524 64 64; Email: recruit@chdr.nl
    • Contact: Jesminne Castricum, PhD; Phone Number: +31 715246400; Email: jcastricum@chdr.nl
    • Principal Investigator: Philip Kremer, Dr.
    • Sub-Investigator: Daniël Dumas, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VES001 (Healthy Participants); Part A: Ascending single doses and Part B: Multiple ascending dose (seven days of treatment), for healthy volunteers.	Drug: VES001; VES001 is an oral, blood brain barrier penetrating ligand of sortilin.
Placebo Comparator: Placebo (Healthy Participants); Part A: Ascending single doses and Part B: Multiple ascending dose (seven days of treatment), for healthy volunteers.	Drug: Placebo; A matching dosage form, indistinguishable from the active treatment will be used as the placebo treatment.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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.
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.

Collaborators and Investigators

• Sponsor: Vesper Biotechnologies ApS

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2023
• Primary Completion (Estimated): July 16, 2024
• Study Completion (Estimated): August 27, 2024

Study Registration Dates

• First Submitted: December 7, 2023
• First Submitted That Met QC Criteria: January 23, 2024
• First Posted (Estimated): January 26, 2024

Study Record Updates

• Last Update Posted (Estimated): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Dementia; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain
• Other Study ID Numbers: Ph1/VES001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No