Clinical trial NCT06855264: A Cardiac Liability Study of Varegacestat in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: thorough-QT
Lead sponsor: Immunome, Inc.
Sponsor class: INDUSTRY
First posted: 2025-03-03
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Placebo-corrected change from baseline QTc and varegacestat and its metabolite, AL102 MTB, plasma concentrations
timeFrame: 24 hours
Secondary outcomes:
measure: Change from baseline, placebo-corrected, and categorical outliers of the ECG parameter HR from a single oral dose of varegacestat.
timeFrame: 24 hours
measure: Change from baseline and placebo-corrected ECG parameter QT from a single oral dose of varegacestat.
timeFrame: 24 hours
measure: Change from baseline, placebo-corrected, and categorical outliers of the ECG parameter QTcF from a single oral dose of varegacestat.
timeFrame: 24 hours
measure: 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).
timeFrame: 7 days
measure: Maximum observed concentration (Cmax) of varegacesatat and AL102-MTB (varegacestat metabolite).
timeFrame: 7 days
measure: Apparent first-order terminal elimination half-life (t1/2) will be calculated as 0.693/Kel of varegacesatat and AL102-MTB (varegacestat metabolite).
timeFrame: 7 days
measure: Safety and tolerability of a single oral dose of varegacestat by incidences of treatment-emergent adverse events.
timeFrame: Approximately 56 days
measure: Assay sensitivity of the study to detect a small QTc effect using moxifloxacin as a positive control.
timeFrame: 24 hours
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
References: