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

NCT03218995 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 4658-102
• Study Type: interventional
• Target: 15
• Locations: 4 countries
• Sites: 4

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.

Conditions

Duchenne Muscular Dystrophy

Keywords

DMD; Duchenne; Eteplirsen; dystrophy; dystrophin; exon 51

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (4)

• 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

  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)

Study Arms (1)

Eteplirsen

EXPERIMENTAL

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

Interventions

Eteplirsen DRUG

Infusion for intravenous use.

Also known as: AVI-4658, EXONDYS 51®

Eteplirsen

Eligibility Criteria

• Age: 6 Months - 48 Months
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sarepta Therapeutics, Inc.: lead

Study Sites (4)

Universitair ziekenhuis Gent

Ghent, 9000, Belgium

Location

Armand-Trousseau Hospital

Paris, 75012, France

Location

Site Fondazione Policlinico Universitario Agostino Gemelli

Roma, Italy

Location

UCL Great Ormond Street Institute of Child Health

London, WC1N 1EH, United Kingdom

Location

Related Publications (1)

• Mercuri E, Seferian AM, Servais L, Deconinck N, Stevenson H, Ni X, Zhang W, East L, Yonren S, Muntoni F; 4658-102 Study Group. Safety, tolerability and pharmacokinetics of eteplirsen in young boys aged 6-48 months with Duchenne muscular dystrophy amenable to exon 51 skipping. Neuromuscul Disord. 2023 Jun;33(6):476-483. doi: 10.1016/j.nmd.2023.03.008. Epub 2023 Mar 24.

  PMID: 37207382 DERIVED

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

eteplirsen

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Medical Director
• Organization: Sarepta Therapeutics, Inc.

clinicaltrials@sarepta.com

800-690-2003

Study Officials

• Medical Director

  Sarepta Therapeutics, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2017
• First Posted: July 17, 2017
• Study Start: August 16, 2017
• Primary Completion: March 10, 2021
• Study Completion: March 10, 2021
• Last Updated: December 9, 2021
• Results First Posted: December 9, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); FR (1); BE (1); IT (1)