CompletedPhase 2

Mutation-specific Therapy for the Long QT Syndrome

Italy16 participantsStarted 2021-06-15

Plain-language 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.

Who can participate

Age range

18 Years – 65 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Informed consent: it is requested that the partipants understand the nature of the study and can give their voluntary conset after being fully informed, after having received satisfying replies to their questions regarding the study, and all the authorizations according to local requirements. The informed consent form was previously approved by the local Ethics Committee and will have to be dated and signed before enrollment in the study. * Age and gender: participants of both the male and female sex aged between 18 and 65 years will be included * Mutations: the study will enrol patients with LQT2, i.e., with pathogenic mutations on the KCNH2 gene, that present such functional characterization that classifies them as class II mutations, namely mutations that cause a trafficking defect. This characterization includes, but is not limited to, patch clamp data in single cells, immunofluorescence data, positive reactions to drugs that correct the trafficking defect in vitro. * Consent of the patient to not participate in any other clinical study during the entire period of participation in the present study * Women with child-bearing potential (pre-menopausal women, less than two years after start of menopause and women who are not surgically sterile) must use a highly effective contraceptive method from 30 days before enrollment in the study until 28 days after the last administration of study drug. It is specified that the sole use of hormonal contraceptio…

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

QT interval

Timeframe: 3 to 7 days after start of treatment

Trial details

NCT IDNCT04581408

SponsorIstituto Auxologico Italiano

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2025-04-15

View on ClinicalTrials.gov More Long QT Syndrome trials