Long QT Syndrome (LQTS) 2Phase 2/3Wave IINCT07277582
Evaluation of the Efficacy and Safety of THRV-1268 in Participants With Long QT Syndrome Type 2 (LQTS2) and Type 3 (LQTS3)
A Phase 2/3 study testing baseline lead-in and THRV-1268 in people with Long QT Syndrome (LQTS) 2, run by Thryv Therapeutics, Inc. at 9 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Long QT Syndrome (LQTS) 2
- What is being tested?
- baseline lead-in and THRV-1268
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 9 sitesUnited States
- Study dates
- 7 Mar 2026to 30 Jun 2027
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 26Show fewer
- 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.
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
United States9 sites, 9 recruiting
- Not yet recruiting
University of Michigan
Arbor, Michigan, 48109
- Recruiting
Heart Center Clinical Research Program | MGH
Boston, Massachusetts, 02114
- Recruiting
University of Illinois Chicago
Chicago, Illinois, 60612
- Not yet recruiting
NYU Langone Health
New York, New York, 10016
- Recruiting
Oregon Health & Science University
Portland, Oregon, 97239
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
- Recruiting
University of California San Francisco
San Francisco, California, 94143
- Recruiting
Honor Health Research and Innovation Institute
Scottsdale, Arizona, 85258
- Recruiting
Wilmington Health
Wilmington, North Carolina, 28401
About this study
Official title: 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) and Type 3 (LQTS 3)
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:
Read more
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.
- Conditions
- Long QT Syndrome (LQTS) 2
- Being tested
- baseline lead-in, THRV-1268
- Medical subject headings
- Long QT Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
baseline lead-inOther
Participants will undergo a 3 weeks run-in baseline
THRV-1268Drug
THRV-1268 50 mg bid (total daily 100 mg) for 6 weeks
THRV-1268Drug
THRV-1268 100 mg bid (total daily 200 mg) for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Other: baseline lead-in; Drug: THRV-1268 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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
QTcF values at each timepoint on Days 42 and 84 will be compared to the time-matched QTcF values on Baseline (mean of Day -7 and Day -1).
Measured: 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
ΔAUC0-12/12 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).
Measured: 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
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) in patients with mean baseline AUC(0-6)/6 QTcF >500 ms.
Measured: Day 42 and Day 84
Part A: To evaluate the maximal shortening in QTcF from pre-dose to post-dose
Measure the maximum delta between pre-dose QTcF (mean baseline values at Day-7 and Day-1) and lowest QTcF values reported on Day 42 and Day 84.
Measured: Day 42 and Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2025
- Study start7 Mar 2026
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Long QT Syndrome (LQTS) 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Thryv Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07277582
- Sponsor's protocol ID
- THRV-1268-0392
- Acronym
- Wave II
- Status last verified
- Jun 2026
- First submitted
- 2 Dec 2025
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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) and Type 3 (LQTS 3)
- ClinicalTrials.gov ID
- NCT07277582
- Acronym / sponsor ID
- Wave II / THRV-1268-0392
- Conditions
- Long QT Syndrome (LQTS) 2
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- Thryv Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 7 Mar 2026 (actual)
- Primary completion
- 30 Jun 2027 (estimated)
- Study completion
- 30 Jun 2027 (estimated)
- First posted
- 11 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| THRV-1268 | Experimental | Other: baseline lead-in, Drug: THRV-12683 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) |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| baseline lead-inParticipants will undergo a 3 weeks run-in baseline | Other | THRV-1268 |
| THRV-1268THRV-1268 50 mg bid (total daily 100 mg) for 6 weeks | Drug | THRV-1268 |
| THRV-1268THRV-1268 100 mg bid (total daily 200 mg) for 6 weeks | Drug | THRV-1268 |
Primary outcome
Part A: To evaluate the effect of oral THRV-1268 on QTcF interval by AUC method in participants with LQTS 2
Time frame: 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])
Time frame: 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.
4 secondary outcomes
Part A: To evaluate the effects of oral THRV-1268 on QTcF interval by various methods in participants with LQTS 2
Time frame: 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
Time frame: 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
Time frame: Day 42 and Day 84
Part A: To evaluate the maximal shortening in QTcF from pre-dose to post-dose
Time frame: Day 42 and Day 84
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
Related trials for Long QT Syndrome (LQTS) 2
Active, not recruitingObservational study
Observational Study to Describe Health-Related Quality of Life and Measure Disease Burden Among Patients With Long QT Syndrome Types (LQTS) 2 and 3
Long QT Syndrome Type 3, Long QT Syndrome 2
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing baseline lead-in and THRV-1268 in people with Long QT Syndrome (LQTS) 2, run by Thryv Therapeutics, Inc. at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Director (1-855-958-WAVE (9283), waveiistudyteam@thryvtrx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: To evaluate the effect of oral THRV-1268 on QTcF interval by AUC method in participants with LQTS 2 (time frame: Day 42 and Day 84). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.