Safety Study of Eteplirsen to Treat Early Stage Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) Clinical Trial

Official title:

An Open-Label, Multi-Center Study to Evaluate the Safety, Efficacy and Tolerability of Eteplirsen in Early Stage Duchenne Muscular Dystrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02420379
• Other study ID #: 4658-203
• Status: Completed
• Phase: Phase 2
• Start date: June 30, 2015
• Est. completion date: December 17, 2018

Study information

• Verified date: December 2020
• Source: Sarepta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Safety, including adverse event monitoring and routine laboratory assessments, will be followed on an ongoing basis for all patients. Clinical efficacy, including functional tests and MRI, will be assessed at regularly scheduled study visits. Patients will undergo one baseline and one follow-up muscle biopsy. Population and serial PK will be collected.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: December 17, 2018
• Est. primary completion date: December 17, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 6 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy (DMD)
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

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

Locations

Country	Name	City	State
United States	Children's Hospital of Atlanta	Atlanta	Georgia
United States	Rare Disease Research Center	Atlanta	Georgia
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Florida, Shands Hospital	Gainesville	Florida
United States	University of Iowa Children's Hospital	Iowa City	Iowa
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Neuromuscular Research Center of Arizona	Phoenix	Arizona
United States	Shriners Hospital for Children	Portland	Oregon
United States	University of California, Davis Medical Center	Sacramento	California
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Seattle Children's Hospital	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Sarepta Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Change From Baseline in Dystrophin Protein Levels Quantified by Western Blot at Week 48 and 96	Change from baseline in dystrophin protein levels (in muscle biopsy samples) were determined by Western blot at Week 48 and 96 was reported. For each time point, 2 blocks of tissues were analyzed by Western blot, each with 2 replicates of gels to determine the dystrophin level as compared to a healthy individual (Percent Normal). The block average value from 2 replicate gels was computed. The overall average was calculated as the mean of the block average values. The overall average values were used for all analyses. In case only 1 gel was available for a block, then that value was used as the block average value.	Baseline, Week 48 and 96
Secondary	Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 and 96	Change from baseline in dystrophin intensity levels (in muscle biopsy samples) was determined by Immunohistochemistry at Week 48 and 96 was reported.	Baseline, Week 48 and 96