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Trial record 1 of 20 for:    exon 51 | DMD
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Study of Eteplirsen in Young Participants With Duchenne Muscular Dystrophy (DMD) Amenable to Exon 51 Skipping

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03218995
Recruitment Status : Completed
First Posted : July 17, 2017
Results First Posted : December 9, 2021
Last Update Posted : December 9, 2021
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: Eteplirsen Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Safety, Tolerability, and Pharmacokinetics Study of Eteplirsen in Young Patients With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping
Actual Study Start Date : August 16, 2017
Actual Primary Completion Date : March 10, 2021
Actual Study Completion Date : March 10, 2021


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®




Primary Outcome Measures :
  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation From Study Drug [ Time Frame: 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.

  2. Number of Participants With at Least 1 Potentially Clinically Significant Clinical Safety Laboratory Abnormality [ Time Frame: 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

  3. Number of Participants With at Least 1 Markedly Abnormal Vital Sign [ Time Frame: 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.

  4. Abnormal Changes From Baseline or Worsening of Physical Examination Findings [ Time Frame: 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.

  5. Number of Participants With at Least 1 Markedly Abnormal Electrocardiogram (ECG) and Echocardiogram (ECHO) [ Time Frame: 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 :
  1. 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) ]
  2. 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) ]
  3. 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) ]
  4. Amount of Drug Eliminated in Urine [ 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 unchanged drug excreted in urine from time 0 to 4 hours after completion of dosing is reported.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 48 Months   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03218995


Locations
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Belgium
Universitair ziekenhuis Gent
Gent, Belgium, 9000
France
Armand-Trousseau Hospital
Paris, France, 75012
Italy
Site Fondazione Policlinico Universitario Agostino Gemelli
Roma, Italy
United Kingdom
UCL Great Ormond Street Institute of Child Health
London, United Kingdom, WC1N 1EH
Sponsors and Collaborators
Sarepta Therapeutics, Inc.
Investigators
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Study Chair: Medical Director Sarepta Therapeutics, Inc.
  Study Documents (Full-Text)

Documents provided by Sarepta Therapeutics, Inc.:
Study Protocol  [PDF] February 7, 2020
Statistical Analysis Plan  [PDF] April 14, 2021

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Responsible Party: Sarepta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03218995    
Other Study ID Numbers: 4658-102
First Posted: July 17, 2017    Key Record Dates
Results First Posted: December 9, 2021
Last Update Posted: December 9, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Sarepta Therapeutics, Inc.:
DMD
Duchenne
Eteplirsen
dystrophy
dystrophin
exon 51
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked