Safety Study of Eteplirsen to Treat Early Stage Duchenne Muscular Dystrophy

NCT02420379 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 4658-203
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 13

Brief Summary

This is an open-label study to assess the safety, tolerability, efficacy and pharmacokinetics of eteplirsen in patients with early stage Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping.

Conditions

Duchenne Muscular Dystrophy (DMD)

Keywords

DMD; Duchenne muscular dystrophy; eteplirsen; Dystrophin; exon 51

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation

  Adverse Event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death; Life-threatening event; required or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly. Treatment emergent adverse events were events that developed or worsened during the on-treatment period (defined as time from first dose of study drug and up to 28 days after last dose of study drug \[up to 100 weeks\]) that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.

  Baseline up to 100 weeks

• Number of Participants With Potentially Clinically Significant Laboratory Abnormalities Reported as TEAEs

  Laboratory parameters included hematology, serum chemistry (SC), urinalysis and coagulation. Number of participants with at least one potentially clinically significant abnormal findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.

  Baseline up to 100 weeks

• Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs

  Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Number of participants with at least one potentially clinically significant abnormal vital signs findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were clinically significant or not clinically significant. Clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.

  Baseline up to 100 weeks

• Number of Participants With at Least One Abnormal Physical Examination Finding

  Physical examinations, full and brief, were performed by the Investigator, a physician Sub-Investigator, or a Nurse Practitioner (if licensed in the state or province to perform physical examinations). Full physical examinations included examination of general appearance; head, ears, eyes, nose, and throat; heart; lungs; chest; abdomen; skin; lymph nodes; and musculoskeletal and neurological systems. Number of participants with at least one abnormal physical examination findings were reported. Abnormality in physical examinations was based on Investigator's discretion.

  Baseline up to 100 weeks

• Number of Participants With Abnormalities in Electrocardiograms (ECGs) Reported as TEAEs

  Twelve-lead ECGs and Holter ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the participant was in the supine position, resting, and quiet for a minimum of 15 minutes. The ECG was manually reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECGs were reported as TEAEs.

  Baseline up to 96 weeks

• Number of Participants With Abnormalities in Echocardiograms (ECHO) Reported as TEAEs

  Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. Cardiac function events included cardiomegaly, tachycardia, and dyspnoea. The ECHO was reviewed and interpreted by medically qualified personnel. Number of participants with at least one abnormalities in ECHO were reported as TEAEs.

  Baseline up to 96 weeks

Secondary Outcomes (2)

• Change From Baseline in Dystrophin Protein Levels Quantified by Western Blot at Week 48 and 96

  Baseline, Week 48 and 96

• Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 and 96

  Baseline, Week 48 and 96

Study Arms (2)

Open-Label

EXPERIMENTAL

Approximately 20 patients will receive weekly infusions of eteplirsen 30 mg/kg .

Drug: eteplirsen

Control Group

NO INTERVENTION

Approximately 20 patients with DMD not amenable to exon 51 skipping will be observed for 96 weeks.

Interventions

eteplirsen DRUG

Eteplirsen 30 mg/kg will be administered as an IV infusion once a week for 96 weeks.

Also known as: AVI-4658, EXONDYS 51®

Open-Label

Eligibility Criteria

• Age: 4 Years - 6 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male 4-6 years of age.
• Diagnosis of DMD, genotypically confirmed.
• Stable dose of oral corticosteroids for at least 12 weeks or has not received corticosteroids for at least 12 weeks.
• Intact right and left biceps muscles or two alternative upper arm muscle groups.
• Parent that is willing to provide consent and comply with study procedures.

You may not qualify if:

• Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks that may have an effect on muscle strength or function (e.g., growth hormone, anabolic steroids).
• Previous or current treatment with any other experimental treatments within 12 weeks or participation in any other clinical trial within 6 months.
• Major surgery within 3 months prior to the first dose of study drug, or planned surgery during this study which would interfere with the ability to perform study activities.
• Presence of other clinically significant illness.

Sponsors & Collaborators

• Sarepta Therapeutics, Inc.: lead

Study Sites (13)

Neuromuscular Research Center of Arizona

Phoenix, Arizona, 85028, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

University of Florida, Shands Hospital

Gainesville, Florida, 32610, United States

Location

Rare Disease Research Center

Atlanta, Georgia, 30318, United States

Location

Children's Hospital of Atlanta

Atlanta, Georgia, 30324, United States

Location

University of Iowa Children's Hospital

Iowa City, Iowa, 52242, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Shriners Hospital for Children

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

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

+1-888-727-3782

Study Officials

• Medical Director

  Sarepta Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2015
• First Posted: April 17, 2015
• Study Start: June 30, 2015
• Primary Completion: December 17, 2018
• Study Completion: December 17, 2018
• Last Updated: January 25, 2021
• Results First Posted: July 22, 2020

Record last verified: 2020-12

Locations

US (13)