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Safety Study of Eteplirsen to Treat Advanced Stage Duchenne Muscular Dystrophy

Primary Purpose

Muscular Dystrophy, Duchenne

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Eteplirsen
Sponsored by
Sarepta Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Muscular Dystrophy, Duchenne focused on measuring DMD, exon 51, dystrophin, dystrophy, eteplirsen, Duchenne

Eligibility Criteria

7 Years - 21 Years (Child, Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Male 7 - 21 years of age
  • Diagnosis of DMD with a mutation that is amenable to exon 51 skipping, confirmed by a genetic report
  • Stable dose of oral corticosteroids for at least 24 weeks or has not received corticosteroids for at least 24 weeks
  • Non-ambulatory, or incapable of walking ≥300 meters on the 6-Minute Walk Test (6MWT).
  • Score of ≤4 on the Brooke Score for Arms and Shoulders.
  • Stable cardiac and pulmonary function
  • Use of contraceptives for sexually active males throughout the study
  • Willing to provide consent and comply with the study

Exclusion Criteria:

  • Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks that may have an effect on muscle strength or function (e.g., growth hormone, anabolic steroids).
  • Previous treatment with SMT C1100/BMN 195 at any time.
  • Previous treatment with drisapersen (PRO051) within the last 6 months.
  • Participation in any other DMD interventional clinical study within 12 weeks
  • Major change in physiotherapy regimen within the past 3 months
  • Major surgery within 3 months
  • Presence of other clinically significant illness
  • Use of an aminoglycoside antibiotic within 12 weeks or the need for this antibiotic or statin during study
  • Forced vital capacity % predicted [FVC % predicted] <40%, or requiring daytime ventilation.
  • Require antiarrhythmic and/or antidiuretic therapy for heart failure.
  • Have a left ventricular ejection fraction (LVEF) of <40%.
  • Prior or ongoing medical condition that could adversely affect the safety of the patient, make it unlikely that the course of treatment would be completed, or impair the assessment of study results.

Sites / Locations

  • Ronald Reagan UCLA Medical Center
  • University of California, Davis Medical Center
  • University of Iowa Children's Hospital
  • Kennedy Krieger Institute
  • Massachusetts General Hospital
  • St. Louis Children's Hospital
  • University of Rochester Medical Center
  • Nationwide Children's Hospital
  • Seattle Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Eteplirsen 30 mg/kg

Arm Description

Participants will receive eteplirsen 30 mg/kg/week intravenous (IV) infusions, weekly, for up to 96 weeks.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment Emergent Adverse Events
An adverse event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; Life-threatening event; Required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events that developed or worsened during the on-treatment period (defined as time from first dose of study drug and up to 28 days after last dose of study drug (up to 100 weeks) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.

Secondary Outcome Measures

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Laboratory parameters included hematology, clinical chemistry, urinalysis and coagulation. Data is only reported for parameters in which at least 1 participant had potentially clinically significant abnormal findings. Incr=increase; LLN=lower limit of normal; ULN=upper limit of normal; GGT=gamma glutamyl transferase
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Data is only reported for parameters in which at least 1 participant had potentially clinically significant abnormal vital sign findings.
Number of Participants With at Least One Potentially Clinically Significant Abnormalities in Physical Examinations
Physical examinations, full and brief, were performed by the Investigator, a physician Sub-Investigator, or a Nurse Practitioner (if licensed in the state or province to perform physical examinations). Full physical examinations included examination of general appearance; head, ears, eyes, nose, and throat; heart; lungs; chest; abdomen; skin; lymph nodes; and musculoskeletal and neurological systems. Brief physical examinations included examination of general appearance; head, ears, eyes, nose, and throat; heart; lungs; chest; abdomen; and skin.
Number of Participants With Abnormalities in Electrocardiograms (ECGs)
Twelve-lead ECGs and Holter ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the patient was in the supine position, resting, and quiet for a minimum of 15 minutes. The ECG was manually reviewed and interpreted by medically qualified personnel using a central vendor according to prespecified criteria. The Investigator reviewed the results of the centrally read ECG report and determined if the findings were clinically significant. Data is only reported for parameters in which at least 1 participant had potentially clinically significant abnormal ECG findings. msec=milliseconds; QTcF=QT interval corrected with Fridericia's method
Number of Participants With Abnormalities in Echocardiograms (ECHO)
Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. The ECHO was reviewed and interpreted by medically qualified personnel using a central vendor according to prespecified criteria. Ejection fraction was noted. The Investigator reviewed the results of the ECHO report and determined if the findings were clinically significant. LEVF=left ventricular ejection fraction

Full Information

First Posted
October 30, 2014
Last Updated
March 26, 2020
Sponsor
Sarepta Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02286947
Brief Title
Safety Study of Eteplirsen to Treat Advanced Stage Duchenne Muscular Dystrophy
Official Title
An Open-Label, Multi-Center Study to Evaluate the Safety and Tolerability of Eteplirsen in Patients With Advanced Stage Duchenne Muscular Dystrophy
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
November 2014 (Actual)
Primary Completion Date
April 21, 2017 (Actual)
Study Completion Date
March 23, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sarepta Therapeutics, Inc.

4. Oversight

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

5. Study Description

Brief Summary
The primary objective of this study is to explore safety and tolerability of eteplirsen in participants with advanced stage Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping.
Detailed Description
This is an open-label, multi-center study to explore the safety and tolerability of eteplirsen injection in participants with advanced stage DMD with confirmed genetic mutations amenable to treatment by exon 51 skipping. Participants will be evaluated for inclusion during a Screening/Baseline period of up to 4 weeks. Eligible participants will receive once weekly intravenous (IV) infusions of 30 mg/kg eteplirsen for 96 weeks, followed by a safety extension (not to exceed 48 weeks). Safety will be regularly assessed throughout the study via the collection of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Dystrophy, Duchenne
Keywords
DMD, exon 51, dystrophin, dystrophy, eteplirsen, Duchenne

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Eteplirsen 30 mg/kg
Arm Type
Experimental
Arm Description
Participants will receive eteplirsen 30 mg/kg/week intravenous (IV) infusions, weekly, for up to 96 weeks.
Intervention Type
Drug
Intervention Name(s)
Eteplirsen
Other Intervention Name(s)
AVI-4658, EXONDYS 51®
Intervention Description
Eteplirsen solution for IV infusion
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events
Description
An adverse event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. A serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; Life-threatening event; Required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events that developed or worsened during the on-treatment period (defined as time from first dose of study drug and up to 28 days after last dose of study drug (up to 100 weeks) that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.
Time Frame
From first dose of drug up to 100 weeks
Secondary Outcome Measure Information:
Title
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Description
Laboratory parameters included hematology, clinical chemistry, urinalysis and coagulation. Data is only reported for parameters in which at least 1 participant had potentially clinically significant abnormal findings. Incr=increase; LLN=lower limit of normal; ULN=upper limit of normal; GGT=gamma glutamyl transferase
Time Frame
Baseline up to 100 weeks
Title
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Description
Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Data is only reported for parameters in which at least 1 participant had potentially clinically significant abnormal vital sign findings.
Time Frame
Baseline up to 100 weeks
Title
Number of Participants With at Least One Potentially Clinically Significant Abnormalities in Physical Examinations
Description
Physical examinations, full and brief, were performed by the Investigator, a physician Sub-Investigator, or a Nurse Practitioner (if licensed in the state or province to perform physical examinations). Full physical examinations included examination of general appearance; head, ears, eyes, nose, and throat; heart; lungs; chest; abdomen; skin; lymph nodes; and musculoskeletal and neurological systems. Brief physical examinations included examination of general appearance; head, ears, eyes, nose, and throat; heart; lungs; chest; abdomen; and skin.
Time Frame
Baseline up to 100 weeks
Title
Number of Participants With Abnormalities in Electrocardiograms (ECGs)
Description
Twelve-lead ECGs and Holter ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the patient was in the supine position, resting, and quiet for a minimum of 15 minutes. The ECG was manually reviewed and interpreted by medically qualified personnel using a central vendor according to prespecified criteria. The Investigator reviewed the results of the centrally read ECG report and determined if the findings were clinically significant. Data is only reported for parameters in which at least 1 participant had potentially clinically significant abnormal ECG findings. msec=milliseconds; QTcF=QT interval corrected with Fridericia's method
Time Frame
Baseline up to 100 weeks
Title
Number of Participants With Abnormalities in Echocardiograms (ECHO)
Description
Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. The ECHO was reviewed and interpreted by medically qualified personnel using a central vendor according to prespecified criteria. Ejection fraction was noted. The Investigator reviewed the results of the ECHO report and determined if the findings were clinically significant. LEVF=left ventricular ejection fraction
Time Frame
Baseline up to 100 weeks

10. Eligibility

Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male 7 - 21 years of age Diagnosis of DMD with a mutation that is amenable to exon 51 skipping, confirmed by a genetic report Stable dose of oral corticosteroids for at least 24 weeks or has not received corticosteroids for at least 24 weeks Non-ambulatory, or incapable of walking ≥300 meters on the 6-Minute Walk Test (6MWT). Score of ≤4 on the Brooke Score for Arms and Shoulders. Stable cardiac and pulmonary function Use of contraceptives for sexually active males throughout the study Willing to provide consent and comply with the study Exclusion Criteria: Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks that may have an effect on muscle strength or function (e.g., growth hormone, anabolic steroids). Previous treatment with SMT C1100/BMN 195 at any time. Previous treatment with drisapersen (PRO051) within the last 6 months. Participation in any other DMD interventional clinical study within 12 weeks Major change in physiotherapy regimen within the past 3 months Major surgery within 3 months Presence of other clinically significant illness Use of an aminoglycoside antibiotic within 12 weeks or the need for this antibiotic or statin during study Forced vital capacity % predicted [FVC % predicted] <40%, or requiring daytime ventilation. Require antiarrhythmic and/or antidiuretic therapy for heart failure. Have a left ventricular ejection fraction (LVEF) of <40%. Prior or ongoing medical condition that could adversely affect the safety of the patient, make it unlikely that the course of treatment would be completed, or impair the assessment of study results.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sarepta Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Ronald Reagan UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of California, Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of Iowa Children's Hospital
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Kennedy Krieger Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
St. Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
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
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

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Safety Study of Eteplirsen to Treat Advanced Stage Duchenne Muscular Dystrophy

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