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

Primary Purpose

Long QT Syndrome Type 3

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Eleclazine
Eleclazine placebo
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Long QT Syndrome Type 3 focused on measuring Type 3 long QT syndrome (LQT3), Long QT syndrome, Congenital long QT, Sudden cardiac death

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Mayo Clinic Rochester
  • NYU Langone Medical Center
  • University of Rochester Medical Center
  • Nova Scotia Health Authority
  • L'institut Du Thorax Nantes
  • Groupe Hospitalier Bichat Claude Bernard
  • CHU Réunion Sud
  • LMU Klinikum der Universität München
  • Tel Aviv Sourasky Medical Center
  • Fondazione Salvatore Maugeri IRCCS
  • Academisch Medisch Centrum Amsterdam
  • Barts and The London School of Medicine and Dentistry

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Eleclazine (Single-blind treatment phase)

Open-label Extension Phase

Arm Description

Eleclazine and/or eleclazine placebo up to Week 24

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
November 21, 2014
Last Updated
December 12, 2017
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT02300558
Brief Title
Effect of Eleclazine on Shortening of the QT Interval, Safety, and Tolerability in Adults With Long QT Syndrome Type 3
Official Title
A Phase 3, Single-Blind Study to Evaluate the Effect of Eleclazine (GS-6615) on Shortening of the QT Interval, Safety, and Tolerability in Subjects With Long QT Syndrome Type 3
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Study Start Date
December 17, 2014 (Actual)
Primary Completion Date
December 12, 2016 (Actual)
Study Completion Date
February 15, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Long QT Syndrome Type 3
Keywords
Type 3 long QT syndrome (LQT3), Long QT syndrome, Congenital long QT, Sudden cardiac death

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
Participant
Allocation
Non-Randomized
Enrollment
41 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eleclazine (Single-blind treatment phase)
Arm Type
Experimental
Arm Description
Eleclazine and/or eleclazine placebo up to Week 24
Arm Title
Open-label Extension Phase
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Eleclazine
Other Intervention Name(s)
GS-6615
Intervention Description
Tablets administered orally
Intervention Type
Drug
Intervention Name(s)
Eleclazine placebo
Intervention Description
Tablets administered orally
Primary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
Baseline; Week 24
Secondary Outcome Measure Information:
Title
Change From Baseline in Mean Daytime QTcF Interval (AUC0-6/6) to Week 12 (Lead V5; Standard 12-lead ECG)
Description
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.
Time Frame
Baseline; Week 12
Title
Change From Baseline in Mean Daily (Daytime and Nocturnal) QTcF Interval to Week 24 (Lead V5; Holter)
Description
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.
Time Frame
Baseline; Week 24
Title
Change From Baseline in Mean Nocturnal QTcF Interval to Week 24 (Lead V5; Holter)
Description
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.
Time Frame
Baseline; Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
NYU Langone Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Nova Scotia Health Authority
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 3A7
Country
Canada
Facility Name
L'institut Du Thorax Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Facility Name
Groupe Hospitalier Bichat Claude Bernard
City
Paris
ZIP/Postal Code
75877
Country
France
Facility Name
CHU Réunion Sud
City
Saint-Pierre
ZIP/Postal Code
97410
Country
France
Facility Name
LMU Klinikum der Universität München
City
München
ZIP/Postal Code
80336
Country
Germany
Facility Name
Tel Aviv Sourasky Medical Center
City
Tel-Aviv
Country
Israel
Facility Name
Fondazione Salvatore Maugeri IRCCS
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Academisch Medisch Centrum Amsterdam
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Barts and The London School of Medicine and Dentistry
City
London
ZIP/Postal Code
EC1M 6BQ
Country
United Kingdom

12. IPD Sharing Statement

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

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