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

Phase 2

Completed

• Conditions: Duchenne Muscular Dystrophy
• Interventions: Drug: Eteplirsen

• Registration Number: NCT03218995
• Lead Sponsor: Sarepta Therapeutics, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-07-09
• Study First Submitted QC: 2017-07-12
• Study First Posted: 2017-07-17
• Study Start: 2017-08-16
• Primary Completion: 2021-03-10
• Study Completion: 2021-03-10
• Status Verified: 2021-11
• Results First Submitted: 2021-11-10
• Results First Submitted QC: 2021-11-10
• Last Update Submitted: 2021-11-10
• Results First Posted: 2021-12-09
• Last Update Posted: 2021-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 15

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Eteplirsen	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug	Baseline up to Week 100	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 Markedly Abnormal Vital Sign	Baseline up to Week 100	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.
Number of Participants With at Least 1 Potentially Clinically Significant Clinical Safety Laboratory Abnormality	Baseline up to Week 100	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
Abnormal Changes From Baseline or Worsening of Physical Examination Findings	Baseline up to Week 100	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)	Weeks 8, 12, 24, 36, 48, 60, 72, 84, 96	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

Name	Time	Method
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)
Amount of Drug Eliminated in Urine	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 unchanged drug excreted in urine from time 0 to 4 hours after completion of dosing is reported.
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)
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)

Trial Locations

Locations (4)

Universitair ziekenhuis Gent; 🇧🇪 Gent, Belgium

Armand-Trousseau Hospital; 🇫🇷 Paris, France

Site Fondazione Policlinico Universitario Agostino Gemelli; 🇮🇹 Roma, Italy

UCL Great Ormond Street Institute of Child Health; 🇬🇧 London, United Kingdom