A Cardiac Liability Study of Varegacestat in Healthy Participants

A Phase 1, Randomized, Single-Dose, Positive- and Placebo-Controlled, 3-Way Crossover Study to Evaluate the Effects of Varegacestat on Cardiac Repolarization in Healthy Participants

This clinical study is designed to study the effect of a single dose of varegacestat on cardiac repolarization in healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: Placebo; Drug: varegacestat; Drug: Moxifloxacin 400 mg

Detailed Description

This is a double-blind (with respect to varegacestat and placebo only), single-dose, randomized, placebo- and positive- controlled, 3-way crossover study.

On Day 1 of each period, participants will receive one of 3 treatments: a single dose of varegacestat (Treatment A), a single dose of varegacestat matching placebo (Treatment B), or a single dose of moxifloxacin (Treatment C). In each period, cardiodynamic ECGs will be collected predose and for 24 hours postdose. PK samples will be collected predose and up to 168 hours post-dose for assessments of varegacestat and AL102 MTB, and up to 24 hours post-dose for assessment of moxifloxacin.

There will be a washout of at least 14 days between doses. Safety will be monitored throughout the study by repeated clinical and laboratory evaluations.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85289
      • Celerion

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy, adult, male or female (of non childbearing potential), 18 to 55 years of age, inclusive, at the screening visit.
• Medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, and vital signs, as deemed by the PI or designee

Exclusion Criteria:

• 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.
• Have taken an investigational drug or participated in a clinical trial evaluating an investigational drug or device within 30 days (or 5 half-lives) prior to the study drug dose, whichever is longer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Single oral dose of placebo
Active Comparator: Moxifloxacin	Drug: Moxifloxacin 400 mg; Single oral dose of moxifloxacin
Experimental: Varegacestat	Drug: varegacestat; Single oral dose of varegacestat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Placebo-corrected change from baseline QTc and varegacestat and its metabolite, AL102 MTB, plasma concentrations	24 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline, placebo-corrected, and categorical outliers of the ECG parameter HR from a single oral dose of varegacestat.	24 hours
Change from baseline and placebo-corrected ECG parameter QT from a single oral dose of varegacestat.	24 hours
Change from baseline, placebo-corrected, and categorical outliers of the ECG parameter QTcF from a single oral dose of varegacestat.	24 hours
The AUC from time 0 extrapolated to infinity, calculated as the sum of AUC0-t plus the ratio of the last measurable plasma concentration to the elimination rate constant of varegacesatat and AL102-MTB (varegacestat metabolite).	7 days
Maximum observed concentration (Cmax) of varegacesatat and AL102-MTB (varegacestat metabolite).	7 days
Apparent first-order terminal elimination half-life (t1/2) will be calculated as 0.693/Kel of varegacesatat and AL102-MTB (varegacestat metabolite).	7 days
Safety and tolerability of a single oral dose of varegacestat by incidences of treatment-emergent adverse events.	Approximately 56 days
Assay sensitivity of the study to detect a small QTc effect using moxifloxacin as a positive control.	24 hours

Collaborators and Investigators

• Sponsor: Immunome, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2025
• Primary Completion (Actual): April 8, 2025
• Study Completion (Actual): May 6, 2025

Study Registration Dates

• First Submitted: February 25, 2025
• First Submitted That Met QC Criteria: February 25, 2025
• First Posted (Actual): March 3, 2025

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 19, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: thorough-QT
• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Moxifloxacin
• Other Study ID Numbers: AL102-502

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