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

Duchenne Muscular Dystrophy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03218995
• Other study ID #: 4658-102
• Status: Completed
• Phase: Phase 2
• Start date: August 16, 2017
• Est. completion date: March 10, 2021

Study information

• Verified date: November 2021
• Source: Sarepta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: March 10, 2021
• Est. primary completion date: March 10, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Months to 48 Months

Eligibility

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.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Eteplirsen
Infusion for intravenous use.

Locations

Country	Name	City	State
Belgium	Universitair ziekenhuis Gent	Gent
France	Armand-Trousseau Hospital	Paris
Italy	Site Fondazione Policlinico Universitario Agostino Gemelli	Roma
United Kingdom	UCL Great Ormond Street Institute of Child Health	London

Sponsors (1)

Lead Sponsor	Collaborator
Sarepta Therapeutics, Inc.

Countries where clinical trial is conducted

Belgium,  France,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)