Evaluation of Efficacy and Safety of THRV-1268 in Long QT Syndrome Type 2 (LQTS 2)

A Phase 2/3, Two-part, Dose-ranging, Adaptive Study to Evaluate Efficacy and Safety of THRV-1268 in Participants Diagnosed With Long QT Syndrome Type 2 (LQTS 2)

NCT07277582•Thryv Therapeutics, Inc.

View on ClinicalTrials.gov

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). 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 tablets twice daily at two dose levels for 6 weeks (Part A) or be randomly assigned to a dose group for 6 weeks (Part B) 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.

Eligibility

Age

15 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Male and female participants over 15 years of age at Screening (at least the first 5 participants enrolled in Part A must be 18 years of age or older).
•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.
•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 2 months prior to Screening, Participant has a history of an aborted cardiac arrest, ICD implantation, or syncopal episode due to a ventricular arrhythmia. Participants can be enrolled after the 2-month period has lapsed.
•History of structural or functional cardiovascular disease, myocardial infarction or stroke or transient ischemic attack (TIA), atrial fibrillation or atrial flutter, heart failure, bundle branch block, angina pectoris, or hemodynamically significant ventricular tachycardia not due to TdP
•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.
+16 more criteria

Locations (6)

Honor Health Research and Innovation Institute

Scottsdale, Arizona, United States

University of California San Francisco

San Francisco, California, United States

University of Illinois Chicago

Chicago, Illinois, United States

Heart Center Clinical Research Program | MGH

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Wilmington Health

Wilmington, North Carolina, United States

Key Dates

Start Date

March 31, 2026

Primary Completion Date

June 30, 2027

Completion Date

June 30, 2027

Last Updated

March 19, 2026

Enrollment

ESTIMATED participants

Conditions

Long QT Syndrome (LQTS) 2

Interventions

baseline lead-in

OTHER

THRV-1268

DRUG

THRV-1268

DRUG

Contacts

Study Director

CONTACT

1-855-958-WAVE waveiistudyteam@thryvtrx.com