Thryv Therapeutics has initiated Wave II, a pivotal Phase 2/3 clinical study evaluating THRV-1268, its oral SGK1 inhibitor, in adults with Long QT Syndrome Type 2 (LQTS2).
This marks a major step toward a first-in-class, disease-modifying therapy for a rare, life-threatening cardiac condition with no approved targeted treatments.
Why Wave II Matters?
Patients with LQTS2 live with persistent arrhythmia risk and limited options.
Key gaps today:
- No FDA-approved therapies that directly reduce QT prolongation
- Treatments largely manage symptoms, not disease drivers
Wave II aims to change that.
Strong Clinical Rationale Behind Wave II
The study builds on two prior programs:
Wave I (LQT-1213)
- Clinically meaningful QTc reductions
- Effective in LQTS Types 2 and 3
- Worked on top of standard-of-care
- Favorable safety profile
Phase 1 Study (THRV-1268)
- Reinforced QTcF reductions
- Supported SGK1 inhibition as a viable mechanism
Together, these studies validated SGK1 inhibition as a way to address the electrophysiologic root cause of QT prolongation.
Wave II Study Design at a Glance
Wave II is a two-part study in adults with genetically confirmed LQTS2.
Part A
- 12-week dose-escalation phase
Part B
- 6-week fixed-dose phase with selected dose
Primary endpoint
- Mean change from baseline in QTc AUC
- Patients with baseline QTc >480 ms
THRV-1268 is administered orally, designed for long-term use.
What Is THRV-1268?
THRV-1268 is a best-in-class SGK1 inhibitor, optimized from earlier compounds.
Key attributes:
- Oral administration
- Designed for chronic therapy
- Targets QT prolongation directly
- Built on extensive non-clinical and clinical validation
U.S. Enrollment and Site Network
- Wave II will recruit across multiple U.S. sites
- First site activated at Wilmington Health, North Carolina
- Lead investigator: Dr. Craig McCotter
Additional sites will open as recruitment expands.
Study details:
- ClinicalTrials.gov: NCT07277582
- Study hub: wavestudies.com/wave-2
Parallel Natural History Study Continues
Thryv is also enrolling patients in myQTwave, a non-interventional study.
Purpose:
- Advance understanding of LQTS2 and LQTS3
- Capture real-world patient experience
The Big Picture
Wave II positions THRV-1268 as:
- A late-stage clinical asset
- A potential first approved therapy targeting QT prolongation
- A meaningful advance for families living with Long QT Syndrome
If successful, this program could redefine how inherited arrhythmias are treated.
