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 Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Infusion for intravenous use.
Universitair ziekenhuis Gent
Ghent, 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
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.
Time frame: 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
Time frame: 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.
Time frame: Baseline up to Week 100
Abnormal Changes From Baseline or Worsening of Physical Examination Findings
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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
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.
Time frame: Weeks 8, 12, 24, 36, 48, 60, 72, 84, 96
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)
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)
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)
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.
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)