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Study of Eteplirsen in Young Participants With Duchenne Muscular Dystrophy (DMD) Amenable to Exon 51 Skipping

Primary Purpose

Duchenne Muscular Dystrophy

Status
Completed
Phase
Phase 2
Locations
International
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 focused on measuring DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51

Eligibility Criteria

6 Months - 48 Months (Child)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Male between 6 months to 48 months of age (inclusive)
  • Diagnosis of DMD with a deletion mutation amenable to exon 51 skipping
  • Parent(s) or legal guardian(s) who is willing to provide written informed consent

Exclusion Criteria:

  • Received treatment that might have an effect on muscle strength or function within 12 weeks prior to dosing
  • Received previous or current treatment with any experimental treatment
  • Clinically significant illness other than DMD
  • Clinically significant laboratory abnormality
  • Any other condition that could interfere with the participation in the study.

Sites / Locations

  • Universitair ziekenhuis Gent
  • Armand-Trousseau Hospital
  • Site Fondazione Policlinico Universitario Agostino Gemelli
  • UCL Great Ormond Street Institute of Child Health

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Eteplirsen

Arm Description

Eteplirsen will be administered once every 7 days by intravenous (IV) infusion starting on Day 1 for up to 96 weeks. The starting dose will be 2 milligrams/kilogram (mg/kg) eteplirsen, with escalation to 4, 10, 20, and 30 mg/kg for 10 weeks, and then participants will continue to receive eteplirsen at 30 mg/kg for the duration of the study.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug
TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the study drug. Abnormalities presented at Baseline were considered AEs if they reoccurred after resolution or worsen during the AE collection period. An SAE was defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Number of Participants With at Least 1 Potentially Clinically Significant Clinical Safety Laboratory Abnormality
Clinical laboratory parameters that were evaluated included Any Grade ≥2 (moderate) or serious event without an alternative etiology that the Investigator deemed was related to study drug Two consecutive drug-related serum creatinine levels ≥2*upper limit of normal (ULN) without an alternative etiology Creatine kinase (CK) levels >50,000 units/liter (U/L) A confirmed, unexplained, increase in gamma glutamyl transferase (GGT) >3*ULN and either an increase in bilirubin >2*ULN or nascent prothrombin time >2*ULN concurrently, without an alternative etiology
Number of Participants With at Least 1 Markedly Abnormal Vital Sign
The vital sign parameters that were evaluated included blood pressure, heart rate, respiration, and temperature. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Abnormal Changes From Baseline or Worsening of Physical Examination Findings
Data not collected during the study for this Outcome Measure. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Number of Participants With at Least 1 Markedly Abnormal Electrocardiogram (ECG) and Echocardiogram (ECHO)
The ECG was manually reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the centrally read ECG report were clinically significant. Clinical significance was defined as any variation in ECG findings that had medical relevance resulting in an alteration in medical care. The ECHO was reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the ECHO report were clinically significant. Clinical significance was defined as any variation in ECHO findings that had medical relevance resulting in an alteration in medical care. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.

Secondary Outcome Measures

Maximum Plasma Concentration (Cmax) of Eteplirsen
Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen
Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma
Amount of Drug Eliminated in Urine
Amount of unchanged drug excreted in urine from time 0 to 4 hours after completion of dosing is reported.

Full Information

First Posted
July 9, 2017
Last Updated
November 10, 2021
Sponsor
Sarepta Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03218995
Brief Title
Study of Eteplirsen in Young Participants With Duchenne Muscular Dystrophy (DMD) Amenable to Exon 51 Skipping
Official Title
An Open-Label Safety, Tolerability, and Pharmacokinetics Study of Eteplirsen in Young Patients With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
August 16, 2017 (Actual)
Primary Completion Date
March 10, 2021 (Actual)
Study Completion Date
March 10, 2021 (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
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, and PK of once-weekly IV infusions of eteplirsen in approximately 12 male participants, ages 6 months to 48 months (inclusive), who have genotypically confirmed DMD with a deletion mutation amenable to exon 51 skipping.

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Eteplirsen
Arm Type
Experimental
Arm Description
Eteplirsen will be administered once every 7 days by intravenous (IV) infusion starting on Day 1 for up to 96 weeks. The starting dose will be 2 milligrams/kilogram (mg/kg) eteplirsen, with escalation to 4, 10, 20, and 30 mg/kg for 10 weeks, and then participants will continue to receive eteplirsen at 30 mg/kg for the duration of the study.
Intervention Type
Drug
Intervention Name(s)
Eteplirsen
Other Intervention Name(s)
AVI-4658, EXONDYS 51®
Intervention Description
Infusion for intravenous use.
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug
Description
TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the study drug. Abnormalities presented at Baseline were considered AEs if they reoccurred after resolution or worsen during the AE collection period. An SAE was defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Time Frame
Baseline up to Week 100
Title
Number of Participants With at Least 1 Potentially Clinically Significant Clinical Safety Laboratory Abnormality
Description
Clinical laboratory parameters that were evaluated included Any Grade ≥2 (moderate) or serious event without an alternative etiology that the Investigator deemed was related to study drug Two consecutive drug-related serum creatinine levels ≥2*upper limit of normal (ULN) without an alternative etiology Creatine kinase (CK) levels >50,000 units/liter (U/L) A confirmed, unexplained, increase in gamma glutamyl transferase (GGT) >3*ULN and either an increase in bilirubin >2*ULN or nascent prothrombin time >2*ULN concurrently, without an alternative etiology
Time Frame
Baseline up to Week 100
Title
Number of Participants With at Least 1 Markedly Abnormal Vital Sign
Description
The vital sign parameters that were evaluated included blood pressure, heart rate, respiration, and temperature. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Time Frame
Baseline up to Week 100
Title
Abnormal Changes From Baseline or Worsening of Physical Examination Findings
Description
Data not collected during the study for this Outcome Measure. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Time Frame
Baseline up to Week 100
Title
Number of Participants With at Least 1 Markedly Abnormal Electrocardiogram (ECG) and Echocardiogram (ECHO)
Description
The ECG was manually reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the centrally read ECG report were clinically significant. Clinical significance was defined as any variation in ECG findings that had medical relevance resulting in an alteration in medical care. The ECHO was reviewed and interpreted by medically qualified personnel using a central vendor according to pre-specified criteria. The Investigator determined if the findings in the ECHO report were clinically significant. Clinical significance was defined as any variation in ECHO findings that had medical relevance resulting in an alteration in medical care. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in the 'Adverse Events' Section.
Time Frame
Weeks 8, 12, 24, 36, 48, 60, 72, 84, 96
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) of Eteplirsen
Time Frame
Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Title
Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen
Time Frame
Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Title
Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma
Time Frame
Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)
Title
Amount of Drug Eliminated in Urine
Description
Amount of unchanged drug excreted in urine from time 0 to 4 hours after completion of dosing is reported.
Time Frame
Pre-infusion, immediately prior to end of infusion, and approximately 1-3 hours and 6-8 hours after completion of infusion during Weeks 2 (2 mg/kg dose level), 6 (10 mg/kg dose level), 8 (20 mg/kg dose level), and 10 and 24 (30 mg/kg dose level)

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
48 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male between 6 months to 48 months of age (inclusive) Diagnosis of DMD with a deletion mutation amenable to exon 51 skipping Parent(s) or legal guardian(s) who is willing to provide written informed consent Exclusion Criteria: Received treatment that might have an effect on muscle strength or function within 12 weeks prior to dosing Received previous or current treatment with any experimental treatment Clinically significant illness other than DMD Clinically significant laboratory abnormality Any other condition that could interfere with the participation in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sarepta Therapeutics, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Universitair ziekenhuis Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Armand-Trousseau Hospital
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Site Fondazione Policlinico Universitario Agostino Gemelli
City
Roma
Country
Italy
Facility Name
UCL Great Ormond Street Institute of Child Health
City
London
ZIP/Postal Code
WC1N 1EH
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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Study of Eteplirsen in Young Participants With Duchenne Muscular Dystrophy (DMD) Amenable to Exon 51 Skipping

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