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

An Open-Label Safety, Tolerability, and Pharmacokinetics Study of Eteplirsen in Young Patients With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping

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.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Eteplirsen

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
• France
  • Paris, France, 75012
    • Armand-Trousseau Hospital
• Italy
  • Roma, Italy
    • Site Fondazione Policlinico Universitario Agostino Gemelli
• United Kingdom
  • London, United Kingdom, WC1N 1EH
    • UCL Great Ormond Street Institute of Child Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Eteplirsen; 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.	Drug: Eteplirsen; Infusion for intravenous use.; Other Names: AVI-4658; EXONDYS 51®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to Week 100
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	Baseline up to Week 100
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.	Baseline up to Week 100
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.	Baseline up to Week 100
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.	Weeks 8, 12, 24, 36, 48, 60, 72, 84, 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax) of Eteplirsen		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)
Time to Reach Maximum Plasma Concentration (Tmax) of Eteplirsen		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)
Area Under Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast) of Eteplirsen in Plasma		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)
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.	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)

Collaborators and Investigators

• Sponsor: Sarepta Therapeutics, Inc.
• Investigators: Study Chair: Medical Director, Sarepta Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2017
• Primary Completion (Actual): March 10, 2021
• Study Completion (Actual): March 10, 2021

Study Registration Dates

• First Submitted: July 9, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 17, 2017

Study Record Updates

• Last Update Posted (Actual): December 9, 2021
• Last Update Submitted That Met QC Criteria: November 10, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: DMD; Duchenne; exon 51; dystrophin; dystrophy; Eteplirsen
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: 4658-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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