HealthyPhase 1NCT05725005
PET Study of Repeated ASN51 in Healthy Volunteers
A Phase 1 study testing ASN51 in people with Healthy, run by Asceneuron S.A. at 1 site in United Kingdom.
Trial summary
This is a phase 1, open-label, dose escalation, positron emission tomography (PET) study to investigate the brain occupancy of O-GlcNAcase, and the pharmacodynamics (PD) response in peripheral blood mononuclear cells (PBMCs), after repeated doses of ASN51 in healthy participants. Read more about this study
- Who is it for?
- Ages 22 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- ASN51
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 26 Jan 2023to 8 Jun 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 22 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Normotensive male volunteer (PET participants).
- Male or female volunteer of non-childbearing potential (PBMC-only participants).
- Deemed healthy on the basis of a clinical history, physical and neurological examination, electrocardiogram (ECG), vital signs, and laboratory tests of blood and urine.
- Agree to follow the contraception requirements of the trial.
- Able to give fully informed written consent.
Who cannot join
- Significant (> 10%) recent weight change.
- Positive tests for hepatitis B and hepatitis C, human immunodeficiency virus (HIV).
- Severe adverse reaction to any drug.
- Sensitivity to trial medication.
- Drug or alcohol abuse.
- Regular consumption of xanthine-containing products.
Show all 23Show fewer
- Frequent use of nicotine-containing products.
- Severe adverse reaction to any drug.
- Sensitivity to trial medication (all participants) or PET imaging radioligand (PET participants).
- Use of over-the-counter medication (with the exception of paracetamol [acetaminophen]) during the 7 days before the first dose of radioligand (PET participants) or trial medication (PBMC participants) (or longer if the medicine is a potential enzyme inducer), or prescribed medication during the 28 days before first dose of radioligand (PET participants) or trial medication (PBMC participants).
- Received vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 2 weeks of screening.
- Participation in other clinical trials of unlicensed medicines.
- Loss of more than 400 milliliters (mL) blood, within the 3 months before the first dose of tracer (PET participants) or trial medication (PBMC participants).
- Clinically relevant abnormal findings at the screening assessment, including ECG abnormalities (all participants) or those identified by MRI scan (PET participants only).
- Acute or chronic illness.
- Clinically relevant abnormal history of or concurrent medical (including neurological or psychiatric) condition.
- Positive columbia-suicide severity rating scale (C-SSRS) result.
- Vegan.
- Possibility that volunteer will not cooperate.
- Unsatisfactory venous access.
- Objection by general practitioner (GP).
- PET participants only: significant exposure to research related radiation (more than 10 millisievert [mSv]) within the previous 12 months.
- Contraindications to arterial cannulation (e.g., allen's test indicates risk) or magnetic resonance imaging (MRI) scanning (e.g., presence of a cardiac pacemaker or other implanted electronic device or a history of claustrophobia).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-label, Positron Emission Tomography Study in Healthy Subjects to Determine the Relationship Between Plasma Concentration and Target Occupancy of ASN51 Following Repeated Oral Doses
This is a phase 1, open-label, dose escalation, positron emission tomography (PET) study to investigate the brain occupancy of O-GlcNAcase, and the pharmacodynamics (PD) response in peripheral blood mononuclear cells (PBMCs), after repeated doses of ASN51 in healthy participants.
Read the detailed description
The clinical data from the first-in-human single- and multiple-ascending dose study of ASN51 (ASN51-101), and the adaptive-design PET study of O-GlcNAcase brain ASN51 occupancy after single oral doses (ASN51-102), showed acceptable safety, tolerability and pharmacokinetics (PK). However, to date, no assessment of receptor occupancy (RO) after multiple doses of ASN51 and at plasma concentrations below the EC50 have been done. Hence, the purpose of this study is to assess brain O-GlcNAcase RO using PET following repeated doses of ASN51. The study will also characterise the PBMC response (including the effect of food), and further assess the safety, tolerability, PK, and PK/RO relationship, after repeated ASN51 doses.
The results of this study will be used to select doses for subsequent studies in participants.
- Conditions
- Healthy
- Being tested
- ASN51
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASN51Drug
Oral capsule
| Study group | Role | What they receive |
|---|---|---|
| Group 1: ASN51 Low Dose | Experimental | Participants received low dose of ASN51, orally, once-daily (QD) for 14 days in fasted or fed state. Receives: Drug: ASN51 |
| Group 2: ASN51 High Dose | Experimental | Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state. Receives: Drug: ASN51 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
Protein O-GlcNAcylation in PBMCs at different time-point is reported.
Measured: Pre-dose on Days 1, 2, 11, and 14; 8 hours post-dose on Day 1, 11 and 14; 12 hours post-dose on Day 1 and 14, 24 hours post-dose on Day 15; 72 hours post-dose on Day 17; 144 hours post-dose on Day 20
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan
Regional VT of [18F]-IMA601 in frontal lobe at each brain scan was measured with a PET scan. Participants received an intravenous (IV) dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
Measured: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Regional VT of [18F]-IMA601 in anterior cingulate at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
Measured: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Regional VT of [18F]-IMA601 in Caudate at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
Measured: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Regional VT of [18F]-IMA601 in Putamen at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan.
Participant wise data was reported for this outcome measure.
Measured: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Regional VT of [18F]-IMA601 in Accumbens at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
Measured: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Regional VT of [18F]-IMA601 in Amygdala at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
Measured: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Regional VT of [18F]-IMA601 in cerebral white matter at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
Measured: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Secondary outcomes (27)
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with that treatment. A TEAE is defined as an AE that emerges during treatment (having been absent before treatment) or that worsens after treatment. Serious TEAE is defined as any adverse event that is fatal, is life-threatening, requires or prolongs in-patient treatment, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect.
Measured: Up to 4.5 months
Number of Participants With Clinically Significant Abnormalities in Vital Signs
Vital signs including blood pressure, pulse rate, tympanic temperature, and respiratory rate were assessed. Number of participants with clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator.
Measured: Up to 4.5 months
Number of Participants With Clinically Significant Abnormal 12-lead Safety Electrocardiogram (ECG) Findings
ECG parameters including Ventricular rate, QRS complex of the ECG reflects the rapid depolarization of the right and left ventricles (QRS) interval, portion of the ECG between consecutive R waves, representing the ventricular rate (PR) interval, and QTc interval with Fridericia's correction method (QTcF) was measured. Number of participants with clinically significant abnormal ECG findings were reported. Clinical significance was determined by the investigator.
Measured: Up to 4.5 months
Number of Participants With Clinically Significant Abnormal Physical Examinations
Complete physical examination including general appearance; head, ears, eyes, nose and throat; thyroid; lymph nodes; back and neck; heart; chest; lungs; abdomen; skin; and extremities were performed. Number of participants with clinically significant abnormal physical examinations were reported. Clinical significance was determined by the investigator.
Measured: Up to 4.5 months
Number of Participants With Clinically Significant Abnormal Neurological Examinations Findings
Complete neurological examinations including motor system, romberg test, coordination, and direct pupillary reflexes were performed. Number of participants with clinically significant abnormal neurological examinations findings were reported. Clinical significance was determined by the investigator.
Measured: Up to 4.5 months
Number of Participants With Clinically Significant Changes in Laboratory Parameters
Laboratory tests including hematology, clinical chemistry, coagulation, serology, follicle stimulating hormone (FSH) test (only for females), and urinalysis were performed. Number of participants with clinically significant changes in laboratory parameters were reported. Clinical significance was determined by the investigator.
Measured: Up to 4.5 months
Number of Participants With Suicidal Ideation According to Columbia - Suicide Severity Rating Scale (C-SSRS) Ideation
The C-SSRS is a valid and reliable suicidal scale that includes a seven-item subscale that asks participants to self-report on actual attempts, interrupted attempts, aborted attempts, and preparatory acts or behaviors. The suicidal ideation section is rated on a scale from 1 to 5, with higher score indicating a greater severity of suicidal ideation or risk of suicidal behavior. Participants who respond "yes" to any question related to suicidal ideation are reported in this outcome measure.
Measured: Up to 4.5 months
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Measured: Day 1: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours; Day 11: 8 hours; Day 14: 0.25, 0.5, 1, 2, 4, 6, 12 hours; Day 15, Day 16, Day 17, Day 18, Day 20, and Day 23
Maximum Observed Plasma Concentration (Cmax) of ASN51
Cmax was obtained directly from the concentration-time data.
Measured: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1; Pre-dose, and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Dose-normalised Cmax (Cmax/Dose) of ASN51
Calculated as Cmax /Dose administered.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1; Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Time to Reach Maximum Observed Plasma Concentration (Tmax) of ASN51
The tmax was obtained directly from the concentration-time data.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1; Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of ASN51
AUCinf was calculated using the trapezoidal method for the interval 0 to tlast (time tlast is the time at which the last non-zero level was recorded), plus the area under the exponential curve from tlast to infinity.
Measured: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Dose-normalised AUC Infinity (AUCinf /D) of ASN51
Calculated as AUCinf /Dose administered. Here, the unit of measure is represented as hours*nanograms per milliliters per milligram (h*ng/mL/mg).
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1, Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of ASN51
AUClast was calculated using the trapezoidal method.
Measured: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of ASN51
AUCtau was calculated using the trapezoidal method.
Measured: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1, Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Terminal Half-life (t1/2) of ASN51
The t1/2 was calculated from the terminal slope of the log concentration-time curve as follows: t1/2 = loge 2 / lambda(λ)z.
Measured: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Terminal Rate Constant (λz) of ASN51
Terminal rate constant was estimated by linear regression of logarithmically transformed concentration versus time data.
Measured: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Apparent Total Clearance From Plasma After Oral Administration (CLss/F) of ASN51 at Steady State
Calculated using the formula as follows: CLss/F = Dose/ AUCtau.
Measured: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Apparent Volume of Distribution After Oral Administration (VZ/F) of ASN51
Calculated using the formula as follows: VZ/F = Dose/λz *AUCtau.
Measured: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Trough Plasma Concentration (Ctrough) of ASN51
Trough plasma concentration i.e., measured concentration at the end of a dosing interval at steady state (taken directly before next administration, and at 1 dosing interval after the final dose) was obtained directly from the concentration-time data.
Measured: Pre-dose on Days 2, 4, 7, 11 and 14; and 8 hours post-dose on Day 11; 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14, and on Day 15
Accumulation Ratio for AUC (Rac[AUC]) of ASN51
Accumulation ratio was calculated from area under the plasma concentration-time curve during a dosing interval at steady state, and after single dose of ASN51.
Measured: Pre-dose up to Day 14
Accumulation Ratio for Cmax (Rac[Cmax]) of ASN51
Rac(Cmax) was calculated from Cmax at steady state and Cmax after single dose.
Measured: Pre-dose up to Day 14
Effect of Food on PBMC Protein O-GlcNAcylation Levels During Repeated Dosing of ASN51
The analysis of the PD response of PBMCs during repeated ASN51 dosing was conducted using ANOVA. Assessments were conducted at pre-dose and 8 hours post-dose on Day 11 (fed state) and Day 14 (fasted state). The ratio of fed to fasted has been reported.
Measured: Predose and 8 hours post-dose on Days 11 and 14
Group 1: Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and Time
Occupancy estimates were plotted against plasma concentrations of ASN51, corresponding to the start of each post-dose PET scan. Participant wise data was reported for this outcome measure.
Row titles include participant number, PET scan session, post-dose time, and plasma concentration.
Measured: At 5.1, 75.9 hours post-dose on Day 1 (Participant 1); 6.0, 196.9 hours post-dose on Day 1 (Participant 2); 5.2, 79.3 hours post-dose on Day 1 (Participant 3) and 5.5 and 77.0 hours post-dose on Day 1 (Participant 4)
Group 2: Estimated O-GlcNAcase RO by Plasma Concentration of ASN51 and Time
Occupancy estimates were plotted against plasma concentrations of ASN51, corresponding to the start of each post-dose PET scan. Participant wise data was reported for this outcome measure.
Row titles include participant number, PET scan session, post-dose time, and plasma concentration.
Measured: At 5.5, 75.6 hours post-dose on Day 1 (Participant 5); 5.3, 75.4 hours post-dose on Day 1 (Participant 6); 4.9, 75.9 hours post-dose on Day 1 (Participant 7) and 5.0 and 220.5 hours post-dose on Day 1 (Participant 8)
Trough of [18F]-IMA601
Measured: Day 1 up to Day 10
Receptor Occupancy as Assessed by Plasma Concentration That Corresponds to 50% Occupancy (EC50)
Change in VT from baseline to post-dose scans were interpreted as an effect of O-GlcNAcase occupancy by ASN51. Occupancy estimates were plotted against plasma concentrations of ASN51, corresponding to the start of each post-dose PET scan. The following model was fitted to the occupancy data set: Occ=100*Cp/Cp+EC50. Where Occ was the target occupancy (%), Cp was measured plasma concentration of ASN51 (ng/ml) and EC50 was the plasma concentration of ASN51 that corresponds to 50% occupancy. Summarized data was reported for all participants.
Measured: Up to 220.5 hours post-dose on Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2023
- Study start26 Jan 2023
- Primary completion4 Apr 2023
- Study completion8 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HealthyStudies 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asceneuron S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hammersmith Medicines Research, Invicro
- Responsible party
- Sponsor
- Investigators
- Adeep Puri, MD, Principal investigator, Hammersmith Medicines Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05725005
- Sponsor's protocol ID
- ASN51-103
- Status last verified
- May 2025
- First submitted
- 30 Dec 2022
- Last updated
- 8 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Positron Emission Tomography Study in Healthy Subjects to Determine the Relationship Between Plasma Concentration and Target Occupancy of ASN51 Following Repeated Oral Doses
- ClinicalTrials.gov ID
- NCT05725005
- Acronym / sponsor ID
- ASN51-103
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Asceneuron S.A.Industry (pharma, biotech, devices)
- Collaborators
- Hammersmith Medicines Research, Invicro
- Study start
- 26 Jan 2023 (actual)
- Primary completion
- 4 Apr 2023 (actual)
- Study completion
- 8 Jun 2023 (actual)
- First posted
- 13 Feb 2023 (actual)
- Results
- Posted 8 May 2025
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, open-label, dose escalation, positron emission tomography (PET) study to investigate the brain occupancy of O-GlcNAcase, and the pharmacodynamics (PD) response in peripheral blood mononuclear cells (PBMCs), after repeated doses of ASN51 in healthy participants.
Detailed description
The clinical data from the first-in-human single- and multiple-ascending dose study of ASN51 (ASN51-101), and the adaptive-design PET study of O-GlcNAcase brain ASN51 occupancy after single oral doses (ASN51-102), showed acceptable safety, tolerability and pharmacokinetics (PK). However, to date, no assessment of receptor occupancy (RO) after multiple doses of ASN51 and at plasma concentrations below the EC50 have been done. Hence, the purpose of this study is to assess brain O-GlcNAcase RO using PET following repeated doses of ASN51. The study will also characterise the PBMC response (including the effect of food), and further assess the safety, tolerability, PK, and PK/RO relationship, after repeated ASN51 doses.
The results of this study will be used to select doses for subsequent studies in participants.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: ASN51 Low Dose | Experimental | Drug: ASN51Participants received low dose of ASN51, orally, once-daily (QD) for 14 days in fasted or fed state. |
| Group 2: ASN51 High Dose | Experimental | Drug: ASN51Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state. |
Who may qualify
- Ages
- 22 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Normotensive male volunteer (PET participants).
- Male or female volunteer of non-childbearing potential (PBMC-only participants).
- Deemed healthy on the basis of a clinical history, physical and neurological examination, electrocardiogram (ECG), vital signs, and laboratory tests of blood and urine.
- Agree to follow the contraception requirements of the trial.
- Able to give fully informed written consent.
Key exclusion criteria (23 listed)
- Significant (> 10%) recent weight change.
- Positive tests for hepatitis B and hepatitis C, human immunodeficiency virus (HIV).
- Severe adverse reaction to any drug.
- Sensitivity to trial medication.
- Drug or alcohol abuse.
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 |
|---|---|---|
| ASN51Oral capsule | Drug | Group 1: ASN51 Low Dose, Group 2: ASN51 High Dose |
Primary outcome
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)
Time frame: Pre-dose on Days 1, 2, 11, and 14; 8 hours post-dose on Day 1, 11 and 14; 12 hours post-dose on Day 1 and 14, 24 hours post-dose on Day 15; 72 hours post-dose on Day 17; 144 hours post-dose on Day 20
Protein O-GlcNAcylation in PBMCs at different time-point is reported.
Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan
Time frame: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in frontal lobe at each brain scan was measured with a PET scan. Participants received an intravenous (IV) dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan
Time frame: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in anterior cingulate at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan
Time frame: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in Caudate at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan
Time frame: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in Putamen at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan
Time frame: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in Accumbens at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan
Time frame: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in Amygdala at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan
Time frame: PET Scan 1 (Baseline), PET Scan 2 (post-dose on Day 1), PET Scan 3 (Day 4 [for participants 1, 2 (Group 2 only) 3, and 4 (Group 1 only)] and Day 9 [for participant 2 in Group 1 only] and Day 10 [for participant 4 in Group 2 only]) after final ASN51 dose
Regional VT of [18F]-IMA601 in cerebral white matter at each brain scan was measured with a PET scan. Participants received an IV dose of the radiolabelled tracer, [18F]-IMA601, at the start of each PET scan. Participant wise data was reported for this outcome measure.
27 secondary outcomes
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Time frame: Up to 4.5 months
Number of Participants With Clinically Significant Abnormalities in Vital Signs
Time frame: Up to 4.5 months
Number of Participants With Clinically Significant Abnormal 12-lead Safety Electrocardiogram (ECG) Findings
Time frame: Up to 4.5 months
Number of Participants With Clinically Significant Abnormal Physical Examinations
Time frame: Up to 4.5 months
Number of Participants With Clinically Significant Abnormal Neurological Examinations Findings
Time frame: Up to 4.5 months
Number of Participants With Clinically Significant Changes in Laboratory Parameters
Time frame: Up to 4.5 months
Number of Participants With Suicidal Ideation According to Columbia - Suicide Severity Rating Scale (C-SSRS) Ideation
Time frame: Up to 4.5 months
Plasma Concentration of ASN51 at Each Post-dose PET Scan
Time frame: Day 1: 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours; Day 11: 8 hours; Day 14: 0.25, 0.5, 1, 2, 4, 6, 12 hours; Day 15, Day 16, Day 17, Day 18, Day 20, and Day 23
Maximum Observed Plasma Concentration (Cmax) of ASN51
Time frame: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1; Pre-dose, and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Dose-normalised Cmax (Cmax/Dose) of ASN51
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1; Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Time to Reach Maximum Observed Plasma Concentration (Tmax) of ASN51
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1; Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of ASN51
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Dose-normalised AUC Infinity (AUCinf /D) of ASN51
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1, Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of ASN51
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of ASN51
Time frame: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 16 hours post-dose on Day 1, Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Terminal Half-life (t1/2) of ASN51
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Terminal Rate Constant (λz) of ASN51
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Apparent Total Clearance From Plasma After Oral Administration (CLss/F) of ASN51 at Steady State
Time frame: Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Apparent Volume of Distribution After Oral Administration (VZ/F) of ASN51
Time frame: Pre-dose, 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14
Trough Plasma Concentration (Ctrough) of ASN51
Time frame: Pre-dose on Days 2, 4, 7, 11 and 14; and 8 hours post-dose on Day 11; 0.25, 0.5, 1, 2, 4, 6, and 12 hours post-dose on Day 14, and on Day 15
Accumulation Ratio for AUC (Rac[AUC]) of ASN51
Time frame: Pre-dose up to Day 14
Accumulation Ratio for Cmax (Rac[Cmax]) of ASN51
Time frame: Pre-dose up to Day 14
Effect of Food on PBMC Protein O-GlcNAcylation Levels During Repeated Dosing of ASN51
Time frame: Predose and 8 hours post-dose on Days 11 and 14
Group 1: Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and Time
Time frame: At 5.1, 75.9 hours post-dose on Day 1 (Participant 1); 6.0, 196.9 hours post-dose on Day 1 (Participant 2); 5.2, 79.3 hours post-dose on Day 1 (Participant 3) and 5.5 and 77.0 hours post-dose on Day 1 (Participant 4)
Group 2: Estimated O-GlcNAcase RO by Plasma Concentration of ASN51 and Time
Time frame: At 5.5, 75.6 hours post-dose on Day 1 (Participant 5); 5.3, 75.4 hours post-dose on Day 1 (Participant 6); 4.9, 75.9 hours post-dose on Day 1 (Participant 7) and 5.0 and 220.5 hours post-dose on Day 1 (Participant 8)
Trough of [18F]-IMA601
Time frame: Day 1 up to Day 10
Receptor Occupancy as Assessed by Plasma Concentration That Corresponds to 50% Occupancy (EC50)
Time frame: Up to 220.5 hours post-dose on Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
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.
Adeep Puri, MD principal investigator
Hammersmith Medicines Research
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 ASN51 in people with Healthy, run by Asceneuron S.A. at 1 site in United Kingdom.
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 5 inclusion and 23 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 8 May 2025. 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 United Kingdom. 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. 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?
Yes. Results are posted in the registry (first posted 8 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs) (time frame: Pre-dose on Days 1, 2, 11, and 14; 8 hours post-dose on Day 1, 11 and 14; 12 hours post-dose on Day 1 and 14, 24 hours post-dose on Day 15; 72 hours post-dose on Day 17; 144 hours post-dose on Day 20). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 May 2025.