Phase 1
Completed N=12
PET Study of Repeated ASN51 in Healthy Volunteers
Healthy
Source: ClinicalTrials.gov NCT05725005 ↗
Enrolled (actual)
12
Serious AEs
0.0%
Results posted
May 2025
Primary outcomePrimary: Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs) — 100.0; 100.0; 219.33; 232.79 percentage of protein O-GlcNAcylation
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs) |
100.0; 100.0; 219.33; 232.79; 291.02; 190.48 | — |
| PRIMARY Regional Total Volume of Distribution (VT) of [18F]-IMA601 in Frontal Lobe at Each Brain Scan |
11.47; 15.91; 1.97; 1.60; 2.68; 3.67 | — |
| PRIMARY Regional VT of [18F]-IMA601 in Anterior Cingulate at Each Brain Scan |
13.57; 18.51; 1.97; 1.60; 2.85; 3.98 | — |
| PRIMARY Regional VT of [18F]-IMA601 in Caudate at Each Brain Scan |
8.25; 13.28; 1.21; 1.23; 1.76; 2.97 | — |
| PRIMARY Regional VT of [18F]-IMA601 in Putamen at Each Brain Scan |
12.74; 17.00; 2.03; 1.63; 2.86; 3.89 | — |
| PRIMARY Regional VT of [18F]-IMA601 in Accumbens at Each Brain Scan |
13.16; 19.29; 1.73; 1.51; 2.51; 3.91 | — |
| PRIMARY Regional VT of [18F]-IMA601 in Amygdala at Each Brain Scan |
15.00; 18.91; 2.13; 1.54; 3.13; 4.42 | — |
| PRIMARY Regional VT of [18F]-IMA601 in Cerebral White Matter at Each Brain Scan |
8.39; 10.72; 1.67; 1.32; 2.30; 2.96 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs |
4; 3; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Abnormalities in Vital Signs |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Abnormal 12-lead Safety Electrocardiogram (ECG) Findings |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Abnormal Physical Examinations |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Abnormal Neurological Examinations Findings |
0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Changes in Laboratory Parameters |
0; 0 | — |
| SECONDARY Number of Participants With Suicidal Ideation According to Columbia - Suicide Severity Rating Scale (C-SSRS) Ideation |
0; 0 | — |
| SECONDARY Plasma Concentration of ASN51 at Each Post-dose PET Scan |
4.833; 20.18; 132.9; 232.7; 173.8; 355.3 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of ASN51 |
183; 386; 462; 624 | — |
| SECONDARY Dose-normalised Cmax (Cmax/Dose) of ASN51 |
18.3; 19.3; 46.2; 31.2 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of ASN51 |
1.00; 1.00; 0.767; 2.00 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf) of ASN51 |
20428; 40365 | — |
| SECONDARY Dose-normalised AUC Infinity (AUCinf /D) of ASN51 |
2043; 2018 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of ASN51 |
19655; 36574 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve During a Dosing Interval (AUCtau) of ASN51 |
2527; 4888; 7067; 11237 | — |
| SECONDARY Terminal Half-life (t1/2) of ASN51 |
45.1; 66.0 | — |
| SECONDARY Terminal Rate Constant (λz) of ASN51 |
0.0163; 0.0119 | — |
| SECONDARY Apparent Total Clearance From Plasma After Oral Administration (CLss/F) of ASN51 at Steady State |
1.42; 2.25 | — |
| SECONDARY Apparent Volume of Distribution After Oral Administration (VZ/F) of ASN51 |
92.1; 254 | — |
| SECONDARY Trough Plasma Concentration (Ctrough) of ASN51 |
82.4; 149; 173; 316; 227; 444 | — |
| SECONDARY Accumulation Ratio for AUC (Rac[AUC]) of ASN51 |
2.81; 2.52 | — |
| SECONDARY Accumulation Ratio for Cmax (Rac[Cmax]) of ASN51 |
2.55; 1.74 | — |
| SECONDARY Effect of Food on PBMC Protein O-GlcNAcylation Levels During Repeated Dosing of ASN51 |
0.87; 1.05; 0.94; 0.86 | — |
| SECONDARY Group 1: Estimated O-GlcNAcase Receptor Occupancy (RO) by Plasma Concentration of ASN51 and Time |
92.0; 84.6; 94.3; -16.0; 95.6; 91.3 | — |
| SECONDARY Group 2: Estimated O-GlcNAcase RO by Plasma Concentration of ASN51 and Time |
98.5; 83.4; 98.1; 93.3; 98.1; 91.4 | — |
| SECONDARY Trough of [18F]-IMA601 |
— | — |
| SECONDARY Receptor Occupancy as Assessed by Plasma Concentration That Corresponds to 50% Occupancy (EC50) |
17.6 | — |
Eligibility Criteria
Inclusion Criteria
- 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.
Exclusion Criteria
- 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.
- 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).
Data sourced from ClinicalTrials.gov (NCT05725005). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.