Study in Asymptomatic GRN-FTD Patients to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VES001

NCT06705192 | Completed Phase 1

• 2 other identifiers: Ph1b/FTD0022024-513258-31-00
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 2

Brief Summary

This is an open-label, multiple dosing study in asymptomatic GRN-FTD carriers to investigate the safety, tolerability, PK, and PD of VES001. The study follows a MAD design within a single cohort, investigating 2 distinct dose levels (Dose 1: 360 mg and Dose 2: 900 mg), consecutively over a 3-month period. A total of 6 participants will be recruited over a fixed enrolment period of 6 months.

Conditions

Dementia; Frontotemporal Dementia; Asymptomatic Condition

Outcome Measures

Primary Outcomes (2)

• Change in PGRN levels in CSF at Day 28 and Day 84 compared to baseline

  Three (3) CSF samples will be obtained The total amount of CSF collected from each participant over the duration of the study, will not exceed 55 mL.

  16 weeks

• Change in PGRN levels in plasma at Day 28 and Day 84 compared to baseline

  PD samples will be obtained 32 times

  16 weeks

Secondary Outcomes (11)

• To evaluate the CSF PK profile of VES001 following multiple oral doses in asymptomatic GRN-FTD carriers

  16 weeks

• To evaluate the CSF PK profile of VES001 following multiple oral doses in asymptomatic GRN-FTD carriers

  16 weeks

• To evaluate the CSF PK profile of VES001 following multiple oral doses in asymptomatic GRN-FTD carriers

  16 weeks

• To evaluate the CSF PK profile of VES001 following multiple oral doses in asymptomatic GRN-FTD carriers

  16 weeks

• To evaluate the CSF PK profile of VES001 following multiple oral doses in asymptomatic GRN-FTD carriers

  16 weeks

Study Arms (1)

a single cohort, investigating 2 distinct dose levels (Dose 1: 360 mg and Dose 2: 900 mg)

OTHER

The study follows a MAD design within a single cohort, investigating 2 distinct dose levels (Dose 1: 360 mg and Dose 2: 900 mg), consecutively over a 3-month period. Dose 1 at 360 mg (2 capsules of 180 mg in the morning) Dose 2 at 900 mg (2 capsules of 180 mg in the morning \[360 mg\], 3 capsules of 180 mg in the evening \[540 mg\])

Drug: VES001

Interventions

VES001 DRUG

VES001 is an oral, blood brain barrier ligand of sortilin. VES001 will be administered orally as a solid within a gelatine capsule without excipients; the capsule strength will be 180 mg.

a single cohort, investigating 2 distinct dose levels (Dose 1: 360 mg and Dose 2: 900 mg)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has provided signed informed consent, prior to any study-mandated procedure.
• Has a BMI of ≥ 18 to ≤ 32 kg/m2, and with a minimum weight of 50 kg
• Is an asymptomatic carrier of the GRN mutation, previously confirmed via genetic testing AND historical records (as documented by FRS and FTLD-CDR-NACC-SB) available for review by the investigator
• Note: Genetic testing for GRN mutation status will not be conducted as part of methodology or procedures in this study. The study relies on the previously confirmed GRN mutation data in medical history of the potentially eligible participants.
• In good physical health assessed by the investigator and medical history of the participant, physical examinations (PEs), laboratory tests, ECGs, and vital signs
• Is a FOCBP; as defined in CTFG 2020, must have a negative urine pregnancy test at screening and agree to heterosexual abstinence or the use at least 1 highly effective form of contraception (with a failure rate of \<1% per year when used consistently and correctly), from the start of the screening period through 90 days after the last dose of the study drug (Appendix 3). All females are considered of childbearing potential unless they are postmenopausal (at least 12 consecutive months of amenorrhea in the appropriate age group without other known or suspected cause) or have been sterilised surgically (e.g., hysterectomy, bilateral oophorectomy, bilateral salpingectomy).
• Is a male participant who has not had a vasectomy and is sexually active with FOCBP must agree to use a barrier method of birth control from the start of the screening period through 90 days after the last dose of the study drug
• Is a male participant who must agree not to donate sperm from the start of the screening period, through the study, and for at least 90 days after the last dose of the study drug
• Is a female participant who must agree not to donate ova from the start of the screening period, through the study, and for at least 90 days after the last dose of the study drug
• Has the ability to communicate well with the investigator in the Dutch language (at the Erasmus Medical Centre) or English language (at the UCL) and willing to comply with the study restrictions.

You may not qualify if:

• Has evidence of any active or chronic disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, or that would pose an unacceptable risk to the participant in the opinion of the investigator (following a detailed medical history, physical examination, vital signs \[SBP, DBP, HR, respiratory rate, body temperature\], and 12-lead ECG). Minor deviations from the normal range may be accepted, if judged by the investigator to have no clinical relevance.
• Has a history of any known neurologic disease, cognitive impairment, diagnosed abnormal cognitive decline related to the participant's age, a history of seizure, or (significant) head trauma.
• Has a history of active malignancy within the last 5 years, with the exception of fully resected cell carcinoma of the skin.
• Has clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel, and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before dosing to confirm eligibility or judged to be clinically irrelevant for healthy participants
• Tests positive for HBsAg, HCV Ab, HIV1 Ab, or HIV2 Ab at screening.
• Has SBP greater than 140 (untreated hypertension) or less than 90 mm Hg, and DBP greater than 90 or less than 50 mm Hg at screening.
• Has abnormal findings in the resting ECG at screening defined as:
• QTcF \> 450 or \< 300 msec for males and QTcF \> 470 or \< 300 msec for females
• Notable resting bradycardia (HR \< 45 bpm) or tachycardia (HR \> 100 bpm)
• Personal or family history of congenital long QT syndrome or sudden death attributed to underlying heart disease
• ECG with QRS and/or T-wave judged to be unfavorable for a consistently accurate QT measurement (e.g., neuromuscular artefact that cannot be readily eliminated, arrhythmias, indistinct QRS onset, low amplitude T-wave, merged T- and U-waves, prominent U-waves)
• Has evidence of atrial fibrillation, atrial flutter, complete branch block, Wolf-Parkinson-White Syndrome, or cardiac pacemaker
• Meets criteria that would preclude a LP, such as:
• a local infection at the site of the LP
• \< 50 × 10E3/μL platelet count at screening

Sponsors & Collaborators

• Mads Kjolby: lead

Study Sites (2)

Erasmus University Medical Center

Rotterdam, Netherlands

Location

Leonard Wolfson Experimental Neurology Centre CRF National Hospital for Neurology and Neurosurgery

London, United Kingdom

Location

MeSH Terms

Conditions

Dementia; Frontotemporal Dementia; Asymptomatic Diseases

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mads Kjoelby, MD, PhD

  Vesper Bio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Medical Officer

Study Record Dates

• First Submitted: August 22, 2024
• First Posted: November 26, 2024
• Study Start: December 12, 2024
• Primary Completion: August 5, 2025
• Study Completion: August 5, 2025
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); GB (1)