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

NCT07277582 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: THRV-1268-0392
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Long QT Syndrome (LQTS) 2

Outcome Measures

Primary Outcomes (2)

• Part A: To evaluate the effect of oral THRV-1268 on QTcF interval by AUC method in participants with LQTS 2

  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).

  Day 42 and Day 84

• Part A: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability])

  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.

  up to 52 weeks

Secondary Outcomes (4)

• Part A: To evaluate the effects of oral THRV-1268 on QTcF interval by various methods in participants with LQTS 2

  from 0 to 12 hours on Day 42 and 84

• 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

• 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

• Part A: To evaluate the maximal shortening in QTcF from pre-dose to post-dose

  Day 42 and Day 84

Study Arms (1)

THRV-1268

EXPERIMENTAL

3 weeks lead-in baseline followed by 50 mg BID for 6 weeks with scheduled up-titration to 100 mg BID for another 6 weeks (12 weeks total treatment)

Other: baseline lead-in; Drug: THRV-1268

Interventions

baseline lead-in OTHER

Participants will undergo a 3 weeks run-in baseline

THRV-1268

THRV-1268 DRUG

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

THRV-1268

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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 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.

Sponsors & Collaborators

• Thryv Therapeutics, Inc.: lead

Study Sites (6)

Honor Health Research and Innovation Institute

Scottsdale, Arizona, 85258, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

University of Illinois Chicago

Chicago, Illinois, 60612, United States

RECRUITING

Heart Center Clinical Research Program | MGH

Boston, Massachusetts, 02114, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Wilmington Health

Wilmington, North Carolina, 28401, United States

RECRUITING

MeSH Terms

Conditions

Long QT Syndrome

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Study Director

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2025
• First Posted: December 11, 2025
• Study Start: March 31, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

US (6)