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

NCT02300558 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-372-12342014-000042-30
• Study Type: interventional
• Target: 41
• Locations: 8 countries
• Sites: 12

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.

Conditions

Long QT Syndrome Type 3

Keywords

Type 3 long QT syndrome (LQT3); Long QT syndrome; Congenital long QT; Sudden cardiac death

Outcome Measures

Primary Outcomes (1)

• 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 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.

  Baseline; Week 24

Secondary Outcomes (3)

• Change From Baseline in Mean Daytime QTcF Interval (AUC0-6/6) to Week 12 (Lead V5; Standard 12-lead ECG)

  Baseline; Week 12

• Change From Baseline in Mean Daily (Daytime and Nocturnal) QTcF Interval to Week 24 (Lead V5; Holter)

  Baseline; Week 24

• Change From Baseline in Mean Nocturnal QTcF Interval to Week 24 (Lead V5; Holter)

  Baseline; Week 24

Study Arms (2)

Eleclazine (Single-blind treatment phase)

EXPERIMENTAL

Eleclazine and/or eleclazine placebo up to Week 24

Drug: Eleclazine; Drug: Eleclazine placebo

Open-label Extension Phase

EXPERIMENTAL

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.

Drug: Eleclazine

Interventions

Eleclazine DRUG

Tablets administered orally

Also known as: GS-6615

Eleclazine (Single-blind treatment phase); Open-label Extension Phase

Eleclazine placebo DRUG

Tablets administered orally

Eleclazine (Single-blind treatment phase)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (12)

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Nova Scotia Health Authority

Halifax, Nova Scotia, B3H 3A7, Canada

Location

L'institut Du Thorax Nantes

Nantes, 44093, France

Location

Groupe Hospitalier Bichat Claude Bernard

Paris, 75877, France

Location

CHU Réunion Sud

Saint-Pierre, 97410, France

Location

LMU Klinikum der Universität München

München, 80336, Germany

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

Fondazione Salvatore Maugeri IRCCS

Pavia, 27100, Italy

Location

Academisch Medisch Centrum Amsterdam

Amsterdam, 1105 AZ, Netherlands

Location

Barts and The London School of Medicine and Dentistry

London, EC1M 6BQ, United Kingdom

Location

MeSH Terms

Conditions

Long QT syndrome type 3; Long QT Syndrome; Death, Sudden, Cardiac

Interventions

eleclazine

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Heart Arrest; Death, Sudden; Death

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences

ClinicalTrialDisclosures@gilead.com

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2014
• First Posted: November 25, 2014
• Study Start: December 17, 2014
• Primary Completion: December 12, 2016
• Study Completion: February 15, 2017
• Last Updated: January 12, 2018
• Results First Posted: January 12, 2018

Record last verified: 2017-12

Locations

US (3); IL (1); GB (1); DE (1); NL (1); FR (3); IT (1); CA (1)