PET Study of Repeated ASN51 in Healthy Volunteers

Sponsor

Asceneuron S.A. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05725005

Collaborator

Hammersmith Medicines Research (Other), Invicro (Other)

Enrollment

Location

Arms

3.9

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 1, open-label, dose escalation, PET study to investigate the brain occupancy of O-GlcNAcase, and the PD response in PBMCs, after repeated doses of ASN51 in healthy subjects.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: ASN51	Phase 1

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 PK. However, to date, no assessment of 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 patients.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

This is a phase 1, open-label, dose escalation, PET study to investigate the brain occupancy of O-GlcNAcase, and the PD response in PBMCs, after repeated doses of ASN51 in healthy subjects. Enrolment of up to 12 healthy subjects is planned, in up to 2 groups (Groups 1 and 2). Each group will consist of up to 6 subjects.This is a phase 1, open-label, dose escalation, PET study to investigate the brain occupancy of O-GlcNAcase, and the PD response in PBMCs, after repeated doses of ASN51 in healthy subjects. Enrolment of up to 12 healthy subjects is planned, in up to 2 groups (Groups 1 and 2). Each group will consist of up to 6 subjects.

Masking:

None (Open Label)

Primary Purpose:

Other

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.

Anticipated Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Group 1 will receive 10 mg once-daily (QD) doses of ASN51, by mouth, for 14 days.	Drug: ASN51 ASN51 formulation for oral capsule
Experimental: Group 2 Group 2 will receive 20 mg once-daily (QD) doses of ASN51, by mouth, for 14 days.	Drug: ASN51 ASN51 formulation for oral capsule

Arm

Intervention/Treatment

Experimental: Group 1

Group 1 will receive 10 mg once-daily (QD) doses of ASN51, by mouth, for 14 days.

Drug: ASN51

ASN51 formulation for oral capsule

Experimental: Group 2

Group 2 will receive 20 mg once-daily (QD) doses of ASN51, by mouth, for 14 days.

Drug: ASN51

ASN51 formulation for oral capsule

Outcome Measures

Primary Outcome Measures

Pharmacodynamic (PD) change in peripheral blood mononuclear cell (PBMC) O-GlcNAcylation [Baseline up to Day 20]
PD change in percentage of O-GlcNAcase (OGA) enzyme occupancy [Baseline up to Day 20]

Secondary Outcome Measures

Number of participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Up to 45 days]
Pharmacokinetic (PK) parameter: Cmax [Up to Day 20]
Maximum observed concentration of ASN51 at steady state in plasma
Pharmacokinetic (PK) parameter: Cmax/Dose [Up to Day 20]
Data contains Dose normalized Cmax (normalized to total body dose) (Cmax/Dose) of ASN51
Pharmacokinetic (PK) parameter: Tmax [Up to Day 20]
Data indicates Time to Cmax (Tmax) of ASN51
Pharmacokinetic (PK) parameter: t1/2 [Up to Day 20]
Data contains Terminal half-life (t1/2) of ASN51
Pharmacokinetic (PK) Parameter: λz [Up to Day 20]
Data contains Terminal elimination rate constant (λz) of ASN51
Pharmacokinetic (PK) Parameter: AUC tau [Up to Day 20]
Area under the plasma concentration-time curve during a dosing interval (tau)
Pharmacokinetic (PK) Parameters: AUC0-inf and AUC0-last [Up to Day 20]
Data contain Area under the serum concentration-time curve (AUC) from time zero to infinity (AUC0-inf) and Area under the serum concentration-time curve from time zero to the last quantifiable concentration (AUC0-last) of ASN51
Pharmacokinetic (PK) Parameters: AUC0-inf/Dose [Up to Day 20]
Data contain Dose normalized AUC0-inf (AUC0-inf/Dose)
Pharmacokinetic (PK) Parameter: %AUCextrap [Up to Day 20]
Data contains Percentage of AUC0-inf obtained by extrapolation (%AUCext) of ASN51
Pharmacokinetic (PK) Parameter: CLss/F [Up to Day 20]
Data contains apparent total clearance from plasma after non-intravenous administration calculated at steady state
Pharmacokinetic (PK) Parameter: VZ/F [Up to Day 20]
Data contains apparent volume of distribution after non-intravenous administration calculated at steady state
Pharmacokinetic (PK) Parameter: Ctrough [Up to Day 20]
Trough plasma concentration (measured concentration at the end of a dosing interval at a steady state [taken directly before next administration]) obtained direction from the concentration-time data.
Pharmacokinetic (PK) Parameter: Rac(Cmax) [Up to Day 20]
Accumulation ratio for Cmax calculated from Cmax at steady state and Cmax after a single dose
Pharmacokinetic (PK) Parameter: Rac(AUC) [Up to Day 20]
Accumulation ratio for AUC calculated from AUCtau at steady state and AUCtau after a single dose
Pharmacodynamic (PD) Parameter: Trough [18F]-IMA601 VT [Up to 23 days]
Lowest concentration of [18F]-IMA601 based on the regional total volume of distribution at each brain scan

Eligibility Criteria

Criteria

Ages Eligible for Study:

22 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Normotensive male volunteer (PET subjects)
Male or female volunteer of non-childbearing potential (PBMC-only subjects)
Deemed healthy on the basis of a clinical history, physical and neurological examination, 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 & C, 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 subjects) or PET imaging radioligand (PET subjects)
Use of over-the-counter medication (with the exception of paracetamol [acetaminophen]) during the 7 days before the first dose of radioligand (PET subjects) or trial medication (PBMC subjects) (or longer if the medicine is a potential enzyme inducer), or prescribed medication during the 28 days before first dose of radioligand (PET subjects) or trial medication (PBMC subjects)
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 mL blood, within the 3 months before the first dose of tracer (PET subjects) or trial medication (PBMC subjects)
Clinically relevant abnormal findings at the screening assessment, including ECG abnormalities (all subjects) or those identified by MRI scan (PET subjects only)
Acute or chronic illness
Clinically relevant abnormal history of or concurrent medical (including neurological or psychiatric) condition
Positive C-SSRS result
Vegan
Possibility that volunteer will not cooperate
Unsatisfactory venous access
Objection by General Practitioner (GP)
PET subjects only: significant exposure to research related radiation (more than 10 mSv) within the previous 12 months
Contraindications to arterial cannulation (eg Allen's test indicates risk) or MRI scanning (eg presence of a cardiac pacemaker or other implanted electronic device or a history of claustrophobia)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hammersmith	London		United Kingdom

Sponsors and Collaborators

Asceneuron S.A.
Hammersmith Medicines Research
Invicro

Investigators

Principal Investigator: Adeep Puri, MD, Hammersmith Medicines Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Asceneuron S.A.

ClinicalTrials.gov Identifier:

NCT05725005

Other Study ID Numbers:

ASN51-103

First Posted:

Feb 13, 2023

Last Update Posted:

Feb 16, 2023

Last Verified:

Feb 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Study Results

No Results Posted as of Feb 16, 2023