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)
Overview
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.
Information coming soon.
Sex: ALL
Minimum Age: 15 Years
Healthy Volunteers: No
Age Groups: CHILD, ADULT, OLDER_ADULT
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 95 mm Hg, systolic blood pressure 150 mm Hg.
* At Screening, if the 12-lead triplicate ECG demonstrates any of the following: PR >280 ms; QRS >110 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 100 bpm at rest.
* Atrial pacing rate set to >80 bpm in those participants with atrial pacing.
* Abnormal renal function with an eGFR of 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.