A Varegacestat Hepatic Impairment Study

A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Varegacestat in Participants With or Without Hepatic Impairment

This clinical trial is designed to determine the pharmacokinetics, safety and tolerability of varegacestat in people with impaired liver function compared to people with normal liver function.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer; Hepatic Impairment (HI)
• Intervention / Treatment: Drug: varegacestat

Detailed Description

This is an open-label, single-dose, parallel study to evaluate the effects of varying degrees of impaired hepatic function on the PK, safety, and tolerability of varegacestat in adult participants.

The study will be conducted sequentially. The study will enroll participants with mild (Group 2) and moderate (Group 3) hepatic impairment (HI) and healthy participants with normal hepatic function (Group 1) at a 1:1 ratio. Matched healthy participants may match to more than one participant in the HI groups. Subsequently, if appropriate, the study will enroll participants with severe (Group 4) HI and healthy participants with normal hepatic function (Group 1), as needed, to provide 1:1 matches for Group 4. The decision to conduct Group 4 enrollment will be contingent upon the assessment of the feasibility, PK, and safety data from Groups 1-3.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Texas
    • San Antonio, Texas, United States, 78215
      • The Texas Liver Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria (Healthy Participants):

• Healthy, adult, male or female (of nonchildbearing potential only), 18 to 84 years of age, inclusive, at the screening visit. Participant will be matched by age (± 10 years) and sex to a participant with hepatic impairment (HI). Each healthy participant may be matched to more than 1 participant with HI, but cannot be matched to more than 1 participant within the same HI group.
• Medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, and ECGs as deemed by the PI or designee

Inclusion Criteria (Hepatic Impairment):

• Healthy, apart from HI, adult male or female (of nonchildbearing potential only), 18 to 84 years of age, inclusive, at the screening visit.
• Considered to have HI (of any etiology) that has been clinically stable (no acute episodes of illness due to deterioration in hepatic function) for at least 1 month prior to dosing per the PI and Sponsor and is likely to remain stable throughout the study. To be classified as having hepatic impairment with known medical history of liver disease (with or without a known history of alcohol abuse).
• Has a score on the Child-Pugh scale at screening visit and confirmed at check-in as follows:

Mild: ≥5 and ≤6 [Category A]; or

Moderate: ≥7 and ≤9 [Category B]; or

Severe: ≥10 and ≤15 [Category C].

- Medically healthy, apart from HI, with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, and ECGs as deemed by the PI or designee

Exclusion Criteria (Healthy Volunteers):

• Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
• History of any illness that, in the opinion of the PI or designee, might confound the results of the study or pose an additional risk to the participant by their participation in the study.

Exclusion Criteria (Hepatic Impairment):

Participants must not be enrolled in the study, if they meet any of the following criteria:

• Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
• History or presence of clinically significant medical (except for HI) or psychiatric condition or disease in the opinion of the PI or designee.
• History of any illness that, in the opinion of the PI or designee, might confound the results of the study or pose an additional risk to the participant by their participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; Single oral dose of varegacestat administered on study day 1	Drug: varegacestat; experimental intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK of varegacestat and metabolite from a single oral dose of varegacestat in hepatic impaired adult participants to matched healthy adult participants.	AUC0-t varegacestat and metabolite	Up to 4 weeks
PK of varegacestat and metabolite from a single oral dose of varegacestat in hepatic impaired adult participants to matched healthy adult participants.	AUC0-inf for varegacestat and metabolite	Up to 4 weeks
PK of varegacestat and metabolite from a single oral dose of varegacestat in hepatic impaired adult participants to matched healthy adult participants.	Cmax for varegacestat and metabolite	Up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the safety and tolerability of a single oral dose of varegacestat in hepatic impaired adult participants and in matched healthy adult participants.	Number of subjects who experience treatment emergent adverse events (TEAEs)	Up to 4 weeks
Assess the safety and tolerability of a single oral dose of varegacestat in hepatic impaired adult participants and in matched healthy adult participants.	Number of subjects who experience abnormalities in vital signs and in clinical laboratory tests such as serum chemistry and hematology	Up to 4 weeks
Assess the safety and tolerability of a single oral dose of varegacestat in hepatic impaired adult participants and in matched healthy adult participants.	Number of subjects who experience 12-lead ECG abnormalities	Up to 4 weeks

Collaborators and Investigators

• Sponsor: Immunome, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2025
• Primary Completion (Actual): November 5, 2025
• Study Completion (Actual): March 6, 2026

Study Registration Dates

• First Submitted: January 24, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): February 24, 2025

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: AL102-503

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No