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Safety Study of Eteplirsen to Treat Early Stage Duchenne Muscular Dystrophy

Primary Purpose

Duchenne Muscular Dystrophy (DMD)

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 Duchenne Muscular Dystrophy (DMD) focused on measuring DMD, Duchenne muscular dystrophy, eteplirsen, Dystrophin, exon 51

Eligibility Criteria

4 Years - 6 Years (Child)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Male 4-6 years of age.
  • Diagnosis of DMD, genotypically confirmed.
  • Stable dose of oral corticosteroids for at least 12 weeks or has not received corticosteroids for at least 12 weeks.
  • Intact right and left biceps muscles or two alternative upper arm muscle groups.
  • Parent that is willing to provide consent and comply with study procedures.

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 or current treatment with any other experimental treatments within 12 weeks or participation in any other clinical trial within 6 months.
  • Major surgery within 3 months prior to the first dose of study drug, or planned surgery during this study which would interfere with the ability to perform study activities.
  • Presence of other clinically significant illness.

Sites / Locations

  • Neuromuscular Research Center of Arizona
  • Ronald Reagan UCLA Medical Center
  • University of California, Davis Medical Center
  • Stanford University Medical Center
  • University of Florida, Shands Hospital
  • Rare Disease Research Center
  • Children's Hospital of Atlanta
  • University of Iowa Children's Hospital
  • St. Louis Children's Hospital
  • Nationwide Children's Hospital
  • Shriners Hospital for Children
  • Children's Hospital of Philadelphia
  • Seattle Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Open-Label

Control Group

Arm Description

Approximately 20 patients will receive weekly infusions of eteplirsen 30 mg/kg .

Approximately 20 patients with DMD not amenable to exon 51 skipping will be observed for 96 weeks.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
Adverse Event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. 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 adverse events 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 pre-treatment state. AEs included both serious and non-serious adverse events.
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Reported as TEAEs
Laboratory parameters included hematology, serum chemistry (SC), urinalysis and coagulation. Number of participants with at least one potentially clinically significant abnormal findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs
Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Number of participants with at least one potentially clinically significant abnormal vital signs findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Number of Participants With at Least One Abnormal Physical Examination Finding
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. Number of participants with at least one abnormal physical examination findings were reported. Abnormality in physical examinations was based on Investigator's discretion.
Number of Participants With Abnormalities in Electrocardiograms (ECGs) Reported as TEAEs
Twelve-lead ECGs and Holter ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the participant 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. Number of participants with at least one abnormalities in ECGs were reported as TEAEs.
Number of Participants With Abnormalities in Echocardiograms (ECHO) Reported as TEAEs
Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. Cardiac function events included cardiomegaly, tachycardia, and dyspnoea. The ECHO was reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECHO were reported as TEAEs.

Secondary Outcome Measures

Change From Baseline in Dystrophin Protein Levels Quantified by Western Blot at Week 48 and 96
Change from baseline in dystrophin protein levels (in muscle biopsy samples) were determined by Western blot at Week 48 and 96 was reported. For each time point, 2 blocks of tissues were analyzed by Western blot, each with 2 replicates of gels to determine the dystrophin level as compared to a healthy individual (Percent Normal). The block average value from 2 replicate gels was computed. The overall average was calculated as the mean of the block average values. The overall average values were used for all analyses. In case only 1 gel was available for a block, then that value was used as the block average value.
Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 and 96
Change from baseline in dystrophin intensity levels (in muscle biopsy samples) was determined by Immunohistochemistry at Week 48 and 96 was reported.

Full Information

First Posted
April 10, 2015
Last Updated
December 31, 2020
Sponsor
Sarepta Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02420379
Brief Title
Safety Study of Eteplirsen to Treat Early Stage Duchenne Muscular Dystrophy
Official Title
An Open-Label, Multi-Center Study to Evaluate the Safety, Efficacy and Tolerability of Eteplirsen in Early Stage Duchenne Muscular Dystrophy
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
June 30, 2015 (Actual)
Primary Completion Date
December 17, 2018 (Actual)
Study Completion Date
December 17, 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
This is an open-label study to assess the safety, tolerability, efficacy and pharmacokinetics of eteplirsen in patients with early stage Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping.
Detailed Description
Safety, including adverse event monitoring and routine laboratory assessments, will be followed on an ongoing basis for all patients. Clinical efficacy, including functional tests and MRI, will be assessed at regularly scheduled study visits. Patients will undergo one baseline and one follow-up muscle biopsy. Population and serial PK will be collected.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Open-Label
Arm Type
Experimental
Arm Description
Approximately 20 patients will receive weekly infusions of eteplirsen 30 mg/kg .
Arm Title
Control Group
Arm Type
No Intervention
Arm Description
Approximately 20 patients with DMD not amenable to exon 51 skipping will be observed for 96 weeks.
Intervention Type
Drug
Intervention Name(s)
eteplirsen
Other Intervention Name(s)
AVI-4658, EXONDYS 51®
Intervention Description
Eteplirsen 30 mg/kg will be administered as an IV infusion once a week for 96 weeks.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
Description
Adverse Event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. 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 adverse events 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 pre-treatment state. AEs included both serious and non-serious adverse events.
Time Frame
Baseline up to 100 weeks
Title
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Reported as TEAEs
Description
Laboratory parameters included hematology, serum chemistry (SC), urinalysis and coagulation. Number of participants with at least one potentially clinically significant abnormal findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Time Frame
Baseline up to 100 weeks
Title
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs
Description
Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Number of participants with at least one potentially clinically significant abnormal vital signs findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Time Frame
Baseline up to 100 weeks
Title
Number of Participants With at Least One Abnormal Physical Examination Finding
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. Number of participants with at least one abnormal physical examination findings were reported. Abnormality in physical examinations was based on Investigator's discretion.
Time Frame
Baseline up to 100 weeks
Title
Number of Participants With Abnormalities in Electrocardiograms (ECGs) Reported as TEAEs
Description
Twelve-lead ECGs and Holter ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the participant 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. Number of participants with at least one abnormalities in ECGs were reported as TEAEs.
Time Frame
Baseline up to 96 weeks
Title
Number of Participants With Abnormalities in Echocardiograms (ECHO) Reported as TEAEs
Description
Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. Cardiac function events included cardiomegaly, tachycardia, and dyspnoea. The ECHO was reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECHO were reported as TEAEs.
Time Frame
Baseline up to 96 weeks
Secondary Outcome Measure Information:
Title
Change From Baseline in Dystrophin Protein Levels Quantified by Western Blot at Week 48 and 96
Description
Change from baseline in dystrophin protein levels (in muscle biopsy samples) were determined by Western blot at Week 48 and 96 was reported. For each time point, 2 blocks of tissues were analyzed by Western blot, each with 2 replicates of gels to determine the dystrophin level as compared to a healthy individual (Percent Normal). The block average value from 2 replicate gels was computed. The overall average was calculated as the mean of the block average values. The overall average values were used for all analyses. In case only 1 gel was available for a block, then that value was used as the block average value.
Time Frame
Baseline, Week 48 and 96
Title
Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 and 96
Description
Change from baseline in dystrophin intensity levels (in muscle biopsy samples) was determined by Immunohistochemistry at Week 48 and 96 was reported.
Time Frame
Baseline, Week 48 and 96

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
6 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male 4-6 years of age. Diagnosis of DMD, genotypically confirmed. Stable dose of oral corticosteroids for at least 12 weeks or has not received corticosteroids for at least 12 weeks. Intact right and left biceps muscles or two alternative upper arm muscle groups. Parent that is willing to provide consent and comply with study procedures. 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 or current treatment with any other experimental treatments within 12 weeks or participation in any other clinical trial within 6 months. Major surgery within 3 months prior to the first dose of study drug, or planned surgery during this study which would interfere with the ability to perform study activities. Presence of other clinically significant illness.
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
Neuromuscular Research Center of Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85028
Country
United States
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
Stanford University Medical Center
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Florida, Shands Hospital
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Rare Disease Research Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
Children's Hospital of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30324
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
St. Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Shriners Hospital for Children
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
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 Early Stage Duchenne Muscular Dystrophy

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