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Mutation-specific Therapy for the Long QT Syndrome

NCT04581408 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 16

Last updated 2025-04-25

No results posted yet for this study

Summary

Novel therapy for the Long QT Syndrome based on the mechanism of action of the disease-causing mutations

Long QT syndrome type 2 (LQT2) accounts for \~ 35% of all LQTS cases and is difficult to manage, as beta-blockers frequently fail to provide full protection. Most LQT2 patients (pts) have a Class 2 mutation, which implies defective "trafficking".

Lumacaftor (LUM) is a drug developed and currently indicated for the treatment of cystic fibrosis (CF) in patients homozygous for the F508del mutation in the CFTR gene. LUM corrects protein folding and trafficking defects of mutant and misfolded CFTR channels, restoring their cell surface expression. The investigators recently demonstrated that LUM can rescue in vitro the LQTS phenotype observed in human induced pluripotent stem cell- derived cardiomyocytes (hiPSC-CMs) from pts with LQT2 Class 2 mutations (PMID: 29020304) and in these same two patients Orkambi administrated for 7 days at the same dosage approved for cystic fibrosis showed to reduce their QTc (PMID: 30753398).

With the present phase II clinical trial (MAST2) the investigators will enroll 20 LQT2 patients (see inclusion and exclusion criteria) and they will test in vivo the efficacy of Orkambi in shortening their QTc. Patients will be admitted to hospital for a maximum of 7 days (minimum in-hospital stay based on evidence of QTc shortening). Orkambi will be administered at the dose approved for cystic fibrosis and during the entire period continuous ECG monitoring through both telemetry and 12-lead 24-hr Holter monitoring will be performed and QTc length and morphology will be analyzed.

Conditions

  • Long QT Syndrome

Interventions

DRUG

Lumacaftor / Ivacaftor, Orkambi® Oral Tablet

Total daily dose: 800 mg of Lumacaftor and 500 mg of Ivacaftor. Duration of treatment: according to the clinical conditions of the patient and based on the response to the drugs: up to a maximum of 7 days

Sponsors & Collaborators

  • Istituto Auxologico Italiano

    lead OTHER

Principal Investigators

  • Lia Crotti, MD · Istituto Auxologico Italiano

  • Peter J Schwartz, MD · Istituto Auxologico Italiano

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
65 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2021-06-15
Primary Completion
2025-04-15
Completion
2025-04-15

Countries

  • Italy

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04581408 on ClinicalTrials.gov