Effect of Eleclazine on Shortening of the QT Interval, Safety, and Tolerability in Adults With Long QT Syndrome Type 3

Phase 3

Terminated

Conditions: Long QT Syndrome Type 3

Interventions: Drug: Eleclazine
Drug: Eleclazine placebo

Registration Number: NCT02300558

Lead Sponsor: Gilead Sciences

Brief Summary: The primary objective of this study is to evaluate the effect of oral eleclazine on mean daytime QTcF interval after 24 weeks of treatment with elecalzine in participants with long QT syndrome Type 3. During the single-blind treatment period (24 weeks), participants will receive eleclazine and/or eleclazine placebo. Following the single-blind treatment period, participants who have not permanently discontinued study drug will be eligible, at the discretion of the investigator, to continue receiving eleclazine during an open-label extension (OLE) phase.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 41

Inclusion Criteria

Individuals with an established diagnosis of LQT3 (by genotype testing)
Mean (of triplicate) QTc interval ≥ 480 msec (or ≥ 460 msec, for individuals who are currently taking ranolazine or Class I antiarrhythmic drugs such as mexiletine) at 3 or more time points, determined by standard 12-lead ECG, at screening

Key

Exclusion Criteria

Known mutations associated with type 1 long QT syndrome (LQT1) or type 2 long QT syndrome (LQT2)
Known or suspected history of seizures or epilepsy
History of heart failure defined as New York Heart Association (NYHA) Class IV and/or known left ventricular ejection fraction (EF) ≤ 45%
Body mass index (BMI) ≥ 40 kg/m^2 at screening
Severe renal impairment at screening (defined as an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2, using the 4 Variable Modification of Diet in Renal Disease (MDRD) equation, as determined by the study center)
Abnormal liver function tests at screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN), or total bilirubin > 1.5 x ULN
An aborted cardiac arrest (ACA), implantable cardioverter-defibrillator (ICD) implantation, syncopal episode, or appropriate ICD therapy within 3 months prior to screening
Any other condition or circumstance that in the opinion of the investigator would preclude compliance with the study protocol

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Eleclazine (Single-blind treatment phase)	Eleclazine	Eleclazine and/or eleclazine placebo up to Week 24
Open-label Extension Phase	Eleclazine	Eligible participants will continue to receive open-label eleclazine until this drug is commercially available for the treatment of patients with LQT3, or until Gilead terminates development of eleclazine for the treatment of patients with LQT3, or the investigator deems it no longer in the participant's best interest.
Eleclazine (Single-blind treatment phase)	Eleclazine placebo	Eleclazine and/or eleclazine placebo up to Week 24

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Daytime QT Interval in Lead V5 Corrected for Heart Rate Using the Fridericia Formula (QTcF) Interval to Week 24 (Based on Standard 12-lead ECG Data)	Baseline; Week 24	* Baseline was the Day 1 value. * QTcF is corrected QT interval using Fridericia's formula. QTcF = QT/cube root (RR), where RR is in seconds. * AUC0-6 for QTcF was calculated using the trapezoidal rule, mean of triplicate values, and actual time (latest of triplicate times). * Mean daytime QTcF (AUC0-6/6) was computed by dividing AUC0-6 by the time from dosing to the 6 hour postdose time point.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Daytime QTcF Interval (AUC0-6/6) to Week 12 (Lead V5; Standard 12-lead ECG)	Baseline; Week 12	* Baseline was the Day 1 value. * QTcF is corrected QT interval using Fridericia's formula. QTcF = QT/cube root (RR), where RR is in seconds. * AUC0-6 for QTcF was calculated using the trapezoidal rule, mean of triplicate values, and actual time (latest of triplicate times) . * Mean daytime QTcF (AUC0-6/6) was computed by dividing AUC0-6 by the time from dosing to the 6 hour postdose time point.
Change From Baseline in Mean Daily (Daytime and Nocturnal) QTcF Interval to Week 24 (Lead V5; Holter)	Baseline; Week 24	* Baseline was the Day 1 value. * QTcF is corrected QT interval using Fridericia's formula. QTcF = QT/cube root (RR), where RR is in seconds. * Mean daytime QTcF (AUC0-6/6) was computed by dividing AUC0-6 by the time from the first nonmissing nominal time point to the last nonmissing nominal time point, from predose to 6 hours postdose. Mean nocturnal QTcF (AUC0-6/6) was computed by dividing AUC0-6 by the time from the first nonmissing nominal time point to the last nonmissing nominal time point, from midnight to 6:00 AM. Daily was computed as the average of daytime (AUC0-6/6) and nocturnal (AUC0-6/6), with both values required to compute the average.
Change From Baseline in Mean Nocturnal QTcF Interval to Week 24 (Lead V5; Holter)	Baseline; Week 24	* Baseline was the Day 1 value. * QTcF is corrected QT interval using Fridericia's formula. QTcF = QT/cube root (RR), where RR is in seconds. * Mean nocturnal QTcF (AUC0-6/6) was computed by dividing AUC0-6 by the time from the first nonmissing nominal time point to the last nonmissing nominal time point, from midnight to 6:00 AM.

Trial Locations

Locations (12): Nova Scotia Health Authority
🇨🇦
Halifax, Nova Scotia, Canada
Groupe Hospitalier Bichat Claude Bernard
🇫🇷
Paris, France
CHU Réunion Sud
🇫🇷
Saint-Pierre, France
LMU Klinikum der Universität München
🇩🇪
München, Germany
Tel Aviv Sourasky Medical Center
🇮🇱
Tel-Aviv, Israel
Fondazione Salvatore Maugeri IRCCS
🇮🇹
Pavia, Italy
Academisch Medisch Centrum Amsterdam
🇳🇱
Amsterdam, Netherlands
NYU Langone Medical Center
🇺🇸
New York, New York, United States
L'institut Du Thorax Nantes
🇫🇷
Nantes, France
Mayo Clinic Rochester
🇺🇸
Rochester, Minnesota, United States
University of Rochester Medical Center
🇺🇸
Rochester, New York, United States
Barts and The London School of Medicine and Dentistry
🇬🇧
London, United Kingdom