PET Study of Repeated ASN51 in Healthy Volunteers

NCT05725005 | Completed Phase 1 Results

• 1 other identifier: ASN51-103
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (8)

• Mean Protein O-GlcNAcylation in Peripheral Blood Mononuclear Cells (PBMCs)

  Protein O-GlcNAcylation in PBMCs at different time-point is reported.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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

  Up to 4.5 months

• Number of Participants With Clinically Significant Abnormalities in Vital Signs

  Up to 4.5 months

• Number of Participants With Clinically Significant Abnormal 12-lead Safety Electrocardiogram (ECG) Findings

  Up to 4.5 months

• Number of Participants With Clinically Significant Abnormal Physical Examinations

  Up to 4.5 months

• Number of Participants With Clinically Significant Abnormal Neurological Examinations Findings

  Up to 4.5 months

Study Arms (2)

Group 1: ASN51 Low Dose

EXPERIMENTAL

Participants received low dose of ASN51, orally, once-daily (QD) for 14 days in fasted or fed state.

Drug: ASN51

Group 2: ASN51 High Dose

EXPERIMENTAL

Participants received high dose of ASN51, orally, QD for 14 days in fasted or fed state.

Drug: ASN51

Interventions

ASN51 DRUG

Oral capsule

Group 1: ASN51 Low Dose; Group 2: ASN51 High Dose

Eligibility Criteria

• Age: 22 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Asceneuron S.A.: lead
• Hammersmith Medicines Research: collaborator
• Invicro: collaborator

Study Sites (1)

Hammersmith

London, United Kingdom

Location

Results Point of Contact

• Title: Asceneuron Clinical Research
• Organization: Asceneuron SA

clinicaltrials.gov@asceneuron.com

+ 41 21 353 8245

Study Officials

• Adeep Puri, MD

  Hammersmith Medicines Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2022
• First Posted: February 13, 2023
• Study Start: January 26, 2023
• Primary Completion: April 4, 2023
• Study Completion: June 8, 2023
• Last Updated: May 8, 2025
• Results First Posted: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)