Ireland
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Recruiting Phase 2/3

Evaluation of the Efficacy and Safety of THRV-1268 in Participants With Long QT Syndrome Type 2 (LQTS2) and Type 3 (LQTS3)

NCT07277582 · tracked via the Priya Life Science USA tracker
Sponsor
Thryv Therapeutics, Inc
Phase
Phase 2/3
Started
2026-03-07
Last updated
2026-09-21

Condition(s) studied

Long QT Syndrome (LQTS) 2

Investigational drug(s) / intervention(s)

baseline lead-inTHRV-1268THRV-1268

baseline lead-in: Participants will undergo a 3 weeks run-in baseline

THRV-1268: THRV-1268 50 mg bid (total daily 100 mg) for 6 weeks

THRV-1268: THRV-1268 100 mg bid (total daily 200 mg) for 6 weeks

Study summary

The goal of this clinical trial is to learn whether the study drug THRV-1268 can safely and effectively shorten the QT interval in people diagnosed with Long QT Syndrome Type 2 (LQTS 2) and Long QT Syndrome Type 3 (LQTS 3). The study will also learn about the safety and tolerability of THRV-1268 at different doses.

The main questions this study aims to answer are:

Does THRV-1268 reduce the QTc interval (a measure of the heart's electrical recovery time)?

What side effects or medical problems occur when participants take THRV-1268?

Which dose of THRV-1268 works best and is safest?

Participants will:

Complete a 3-week observation period with ECG and Holter monitoring to establish baseline QTc measurements Take THRV-1268 twice daily at two dose levels for 6 weeks (Part A) or be randomly assigned to a dose group for 6 weeks (Part B - cohort 1)

Have clinic visits and tests to monitor safety and changes in their heart rhythm

May continue taking THRV-1268 for up to 1 year for ongoing safety and efficacy evaluation

Researchers will compare changes in QTc over time and evaluate side effects to determine whether THRV-1268 can help reduce the risk of abnormal heart rhythms and sudden cardiac events in people with LQTS 2 and LQTS 3.

Eligibility

Sex
ALL
Min age
15 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria: * Male and female participants over 15 years of age at Screening (at least the first 3 participants enrolled in Part A must be 18 years of age or older). * Part A and Part B Cohort 1 LQTS 2 genotype: Demonstration of KCNH2 mutation by clinical laboratory test result that is autosomal dominant (heterozygous) and considered to be pathologic or likely pathologic can be included after approval from the sponsor medical monitor or qualified delegate. * Part B, Cohort 2 LQTS 3 genotype: Demonstration of SCN5A mutation by clinical laboratory test result that is autosomal dominant (heterozygous) and considered to be pathologic or likely pathologic for LQTS (and not Brugada syndrome) can be included after approval from the sponsor medical monitor or qualified delegate. * QTcF interval \>480 ms and ≤600 ms based on Screening ECG. * Body weight of at least 45 kg with body mass index between 18.0 and 40.0 kg/m2, inclusively at Screening. * Male and female participants of childbearing potential must agree to use highly effective contraception throughout the duration of the study. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. * Participants age 15 to \<18 years capable of providing signed assent. Exclusion Criteria: * Within 1 month prior to Screening, Participant has a history of an aborted cardiac arrest, ICD implantation, or syncopal episode due to a ventricular arrhythmia. * History of structural or functional cardiovascular disease, myocardial infarction or stroke or transient ischemic attack (TIA), persistent atrial fibrillation or atrial flutter, heart failure, bundle branch block, angina pectoris, or hemodynamically significant ventricular tachycardia not due to TdP. (Individuals with history of paroxysmal atrial fibrillation are allowed if in sinus rhythm at time of screening and enrollment.) * Active or known liver disease. * Active or past oncologic disease, except for non-melanoma skin cancer. * Advanced pulmonary disease that requires more than a steroid inhaler. * Pulmonary artery hypertension. * Is pregnant, lactating, or breastfeeding, or planning to become pregnant. * Has a positive result for the urine pregnancy test at the Screening Visit or the serum pregnancy test at the Day -7 Visit. * Clinically significant abnormal findings on the physical examination or medical history during Screening or Day -21 as deemed by the investigator. * Has experienced an acute illness that has resolved in less than 14 days before the first study drug dose or has had a major illness or hospitalization within 1 month before the first study drug dose. * Has a recent history of alcohol or substance abuse that would pose a risk for the participant's safety and compliance with the study protocol, in the opinion of the investigator. * Has a pacemaker or ICD that is actively used for ventricular pacing. * Is currently taking or anticipates the use of any restricted drugs * Is known at the time of screening to be considering or scheduled to undergo any elective surgical procedure during the study. * Current participation or recent within 1 month of participating in another interventional clinical study. * Screening Visit diastolic blood pressure \>95 mm Hg, systolic blood pressure \<90 or \>150 mm Hg. * At Screening, if the 12-lead triplicate ECG demonstrates any of the following: PR \>280 ms; QRS \>120 ms, or QTcF \>600 ms or ≤480 ms; bundle branch block or significant ST-T wave abnormalities or flat T waves that could interfere with QT analysis. HR \<50 bpm, unless receiving a beta-blocker in which case \<40 bpm, or HR \>100 bpm at rest. * Atrial pacing rate set to \>80 bpm in those participants with atrial pacing. * Abnormal renal function with an eGFR of \<70 mL/min/1.73 m2 (with eGFR calculated by the CKD-EPI formula at Screening). One retest of the exclusionary eGFR value is allowed at the discretion of the investigator. * Has abnormal liver function tests: * ALT, AST, GGT, ALP \> 1.5 the ULN. * Total bilirubin \>ULN. * INR \>1.2 ULN (requires measurement of prothrombin time (PT)). * Has clinically significant abnormality in serum chemistry values at Screening for hemoglobin, potassium, magnesium, or calcium levels as determined by the investigator. A single repeat test and/or correction of abnormal values (e.g., electrolyte repletion) is permitted at the investigator's discretion prior to enrollment. * Any participant, who, for any reason, is deemed by the investigator to be inappropriate for this study or has any condition which would confound or interfere with the evaluation of the safety, tolerability, or efficacy of the investigational medicinal product (IMP) or prevent compliance with the study protocol. * Consumes on average more than 21 standard alcoholic drinks per week in men and 14 standard drinks per week in women over the last 2 years.

Primary outcome measure(s)

  • Part A: To evaluate the effect of oral THRV-1268 on QTcF interval by AUC method in participants with LQTS 2 — Day 42 and Day 84
    ΔAUC0-6 hours QTcF values on Day 42 (THRV-1268 50 mg BID) and Day 84 (THRV-1268 100 mg BID) compared to the the baseline (mean of Day -7 and Day -1).
  • Part A: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) — up to 52 weeks
    To assess the safety and tolerability of two oral dose levels of THRV-1268 in participants with LQTS2 by measuring the incidence of treatment-emergent adverse events throughout the study.

Trial sites (9)

FacilityCityRegionStatus
Honor Health Research and Innovation Institute Scottsdale Arizona Recruiting
University of California San Francisco San Francisco California Recruiting
University of Illinois Chicago Chicago Illinois Recruiting
Heart Center Clinical Research Program | MGH Boston Massachusetts Recruiting
University of Michigan Arbor Michigan Not Yet Recruiting
Mayo Clinic Rochester Minnesota Recruiting
NYU Langone Health New York New York Not Yet Recruiting
Wilmington Health Wilmington North Carolina Recruiting
Oregon Health & Science University Portland Oregon Recruiting
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07277582 on ClinicalTrials.gov ↗ ← All trials in the USA