Dementia, FrontotemporalPhase 1SORT-IN-1NCT06226064
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VES001 in Healthy Participants
A Phase 1 study testing VES001 in people with Dementia, Frontotemporal, run by Vesper Biotechnologies ApS at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Dementia, Frontotemporal
- What is being tested?
- VES001
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 1 siteNetherlands
- Study dates
- 11 Oct 2023to 26 Jul 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy men or women aged 18 to 55 years.
- Body Mass Index between 18 and 32 kg/m2, with a minimum weight of 50 kg.
- Effective contraception required during the study and for at least 90 days after their last dose.
- 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.
Who cannot join
- Medical conditions or treatments that could interfere with the study.
- History of any known neurologic disease, cognitive impairment, or a history of seizure, (significant) head trauma, or loss of consciousness.
- History of active malignancy (active cancer cells or tumors) within the last 5 years.
- Abnormal laboratory test results or infectious diseases (Hepatitis B, Hepatitis C, and/or HIV).
- Recent medication or supplement use, unless allowed by the investigator.
- Participation in other research studies involving study treatment or devices.
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- Positive tests for illegal drugs or alcohol at screening.
- Heavy smoking or inability to abstain from smoking during the study.
- Excessive consumption of caffeine (more than 8 cups per day).
- History of severe allergic reactions to medication
- Recent blood donation or significant blood loss.
- Pregnancy, breastfeeding, or plans to become pregnant (for women).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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).
- Conditions
- Dementia, Frontotemporal
- Being tested
- VES001, Placebo
- Medical subject headings
- Frontotemporal Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VES001Drug
VES001 is an oral, blood brain barrier penetrating ligand of sortilin.
PlaceboDrug
A matching dosage form, indistinguishable from the active treatment will be used as the placebo treatment.
| Study group | Role | What they receive |
|---|---|---|
| VES001 (Healthy Participants) | Experimental | Part A: Ascending single doses and Part B: Multiple ascending dose (seven days of treatment), for healthy volunteers. Receives: Drug: VES001 |
| Placebo (Healthy Participants) | Placebo comparator | Part A: Ascending single doses and Part B: Multiple ascending dose (seven days of treatment), for healthy volunteers. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Incidence of clinically significant abnormalities in safety laboratory values.
Measured: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Pulse Rate (bpm).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Systolic blood pressure (mmHg) and Diastolic blood pressure (mmHg).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter Heart Rate (HR).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter beats per minute (bpm)
Measured: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter PR Interval
Measured: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter QRS Interval
Measured: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter QT Interval.
Measured: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter QTcB (calculated using Bazzet method).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in vital sign measurement: Electrocardiogram parameter QTcF, (calculated using Fredericia's method).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Incidence of clinically significant abnormalities in physical/neurological examination findings.
Measured: Part A: 21 weeks. Part B: 13 weeks.
Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS; Parts B).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Secondary outcomes (14)
Plasma PK parameter: Area under the concentration-time curve from time zero to infinity (AUCinf).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Plasma PK parameter: Area under the concentration-time curve from time zero to infinity AUCinf(%extrapolated).
Measured: 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).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Plasma PK parameter: Apparent total clearance following extravascular administration (CL/F).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Plasma PK parameter: Maximum concentration (Cmax).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Plasma PK parameter: Absorption lag time (tlag).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Plasma PK parameter: Time to reach maximum concentration (tmax).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Plasma PK parameter: Terminal elimination half-life (t1/2).
Measured: 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).
Measured: Part A: 21 weeks. Part B: 13 weeks.
Concentration of VES001 in CSF in the highest two dose level cohorts in Part A.
Measured: Part A: 21 weeks. Part B: 13 weeks.
Concentration of VES001 in CSF in all dose level cohorts in Part B.
Measured: 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.
Measured: Part A: 21 weeks. Part B: 13 weeks.
Concentration of VES001 in plasma/CSF ratio in all dose level cohorts in Part B.
Measured: 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.
Measured: Part A: 21 weeks. Part B: 13 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2024
- Study start11 Oct 2023
- Primary completion26 Jul 2024
- Study completion26 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Dementia, FrontotemporalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vesper Biotechnologies ApS
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mads Kjolby, MD, PhD, Principal investigator, Vesper Bio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06226064
- Sponsor's protocol ID
- Ph1/VES001
- Acronym
- SORT-IN-1
- Status last verified
- Aug 2024
- First submitted
- 7 Dec 2023
- Last updated
- 22 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Klem L, Dumas D, Swift IJ, Frandsen SL, Mikkelsen DN, Fensbaek L, Yavuz Y, Merton O, Castricum J, Prichardt S, Wynne GM, Riisager A, Schultz N, Little PB, Pedersen O, Thijssen E, Nykjaer A, Kremer P, Kjolby M. Preclinical and clinical investigation of VES001, an oral small molecule sortilin receptor inhibitor for the treatment of frontotemporal dementia: a first-in-human randomized placebo-controlled phase 1 trial. Nat Commun. 2026 Sep 14;17(1):10804. doi: 10.1038/s41467-026-77638-2.
PubMed 42875454
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06226064
- Acronym / sponsor ID
- SORT-IN-1 / Ph1/VES001
- Conditions
- Dementia, Frontotemporal
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- Vesper Biotechnologies ApSIndustry (pharma, biotech, devices)
- Study start
- 11 Oct 2023 (actual)
- Primary completion
- 26 Jul 2024 (actual)
- Study completion
- 26 Jul 2024 (actual)
- First posted
- 26 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| VES001 (Healthy Participants) | Experimental | Drug: VES001Part A: Ascending single doses and Part B: Multiple ascending dose (seven days of treatment), for healthy volunteers. |
| Placebo (Healthy Participants) | Placebo comparator | Drug: PlaceboPart A: Ascending single doses and Part B: Multiple ascending dose (seven days of treatment), for healthy volunteers. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy men or women aged 18 to 55 years.
- Body Mass Index between 18 and 32 kg/m2, with a minimum weight of 50 kg.
- Effective contraception required during the study and for at least 90 days after their last dose.
- 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.
Key exclusion criteria (12 listed)
- Medical conditions or treatments that could interfere with the study.
- History of any known neurologic disease, cognitive impairment, or a history of seizure, (significant) head trauma, or loss of consciousness.
- History of active malignancy (active cancer cells or tumors) within the last 5 years.
- Abnormal laboratory test results or infectious diseases (Hepatitis B, Hepatitis C, and/or HIV).
- Recent medication or supplement use, unless allowed by the investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VES001VES001 is an oral, blood brain barrier penetrating ligand of sortilin. | Drug | VES001 (Healthy Participants) |
| PlaceboA matching dosage form, indistinguishable from the active treatment will be used as the placebo treatment. | Drug | Placebo (Healthy Participants) |
Primary outcome
Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs).
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: Systolic blood pressure (mmHg) and Diastolic blood pressure (mmHg).
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.
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 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.
Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS; Parts B).
Time frame: Part A: 21 weeks. Part B: 13 weeks.
14 secondary outcomes
Plasma PK parameter: Area under the concentration-time curve from time zero to infinity (AUCinf).
Time frame: Part A: 21 weeks. Part B: 13 weeks.
Plasma PK parameter: Area under the concentration-time curve from time zero to infinity AUCinf(%extrapolated).
Time frame: 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).
Time frame: Part A: 21 weeks. Part B: 13 weeks.
Plasma PK parameter: Apparent total clearance following extravascular administration (CL/F).
Time frame: Part A: 21 weeks. Part B: 13 weeks.
Plasma PK parameter: Maximum concentration (Cmax).
Time frame: Part A: 21 weeks. Part B: 13 weeks.
Plasma PK parameter: Absorption lag time (tlag).
Time frame: Part A: 21 weeks. Part B: 13 weeks.
Plasma PK parameter: Time to reach maximum concentration (tmax).
Time frame: Part A: 21 weeks. Part B: 13 weeks.
Plasma PK parameter: Terminal elimination half-life (t1/2).
Time frame: 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).
Time frame: Part A: 21 weeks. Part B: 13 weeks.
Concentration of VES001 in CSF in the highest two dose level cohorts in Part A.
Time frame: Part A: 21 weeks. Part B: 13 weeks.
Concentration of VES001 in CSF in all dose level cohorts in Part B.
Time frame: 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.
Time frame: Part A: 21 weeks. Part B: 13 weeks.
Concentration of VES001 in plasma/CSF ratio in all dose level cohorts in Part B.
Time frame: 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.
Time frame: Part A: 21 weeks. Part B: 13 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2024.
- Derived from this study: PubMed 42875454Klem L, Dumas D, Swift IJ, Frandsen SL, Mikkelsen DN, Fensbaek L, Yavuz Y, Merton O, Castricum J, Prichardt S, Wynne GM, Riisager A, Schultz N, Little PB, Pedersen O, Thijssen E, Nykjaer A, Kremer P, Kjolby M. Preclinical and clinical investigation of VES001, an oral small molecule sortilin receptor inhibitor for the treatment of frontotemporal dementia: a first-in-human randomized placebo-controlled phase 1 trial. Nat Commun. 2026 Sep 14;17(1):10804. doi: 10.1038/s41467-026-77638-2.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mads Kjolby, MD, PhD principal investigator
Vesper Bio
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VES001 in people with Dementia, Frontotemporal, run by Vesper Biotechnologies ApS at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence, severity, and seriousness of treatment-emergent adverse events (TEAEs). (time frame: Part A: 21 weeks. Part B: 13 weeks.). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06226064, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2024.