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

Gilead Sciences

Status and phase: Terminated; Phase 3

Conditions: Long QT Syndrome Type 3

Treatments: Drug: Eleclazine; Drug: Eleclazine placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02300558

2014-000042-30 (EudraCT Number)

GS-US-372-1234

Details and patient eligibility

About

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.

Enrollment: 41 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: Single Blind

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41 participants in 2 patient groups

Eleclazine (Single-blind treatment phase)

Experimental group

Description:

Eleclazine and/or eleclazine placebo up to Week 24

Treatment:

Drug: Eleclazine placebo

Drug: Eleclazine

Open-label Extension Phase

Experimental group

Description:

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.

Treatment:

Drug: Eleclazine