Safety Study of Eteplirsen to Treat Advanced Stage Duchenne Muscular Dystrophy

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02286947

Enrollment

Registered

2014-11-10

Start date

2014-11-30

Completion date

2018-03-23

Last updated

2020-03-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Muscular Dystrophy, Duchenne

Keywords

DMD, exon 51, dystrophin, dystrophy, eteplirsen, Duchenne

Brief summary

The primary objective of this study is to explore safety and tolerability of eteplirsen in participants with advanced stage Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping.

Detailed description

This is an open-label, multi-center study to explore the safety and tolerability of eteplirsen injection in participants with advanced stage DMD with confirmed genetic mutations amenable to treatment by exon 51 skipping. Participants will be evaluated for inclusion during a Screening/Baseline period of up to 4 weeks. Eligible participants will receive once weekly intravenous (IV) infusions of 30 mg/kg eteplirsen for 96 weeks, followed by a safety extension (not to exceed 48 weeks). Safety will be regularly assessed throughout the study via the collection of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations.

Interventions

DRUGEteplirsen

Eteplirsen solution for IV infusion

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

7 Years to 21 Years

Healthy volunteers

Inclusion criteria

* Male 7 - 21 years of age * Diagnosis of DMD with a mutation that is amenable to exon 51 skipping, confirmed by a genetic report * Stable dose of oral corticosteroids for at least 24 weeks or has not received corticosteroids for at least 24 weeks * Non-ambulatory, or incapable of walking ≥300 meters on the 6-Minute Walk Test (6MWT). * Score of ≤4 on the Brooke Score for Arms and Shoulders. * Stable cardiac and pulmonary function * Use of contraceptives for sexually active males throughout the study * Willing to provide consent and comply with the study

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 treatment with SMT C1100/BMN 195 at any time. * Previous treatment with drisapersen (PRO051) within the last 6 months. * Participation in any other DMD interventional clinical study within 12 weeks * Major change in physiotherapy regimen within the past 3 months * Major surgery within 3 months * Presence of other clinically significant illness * Use of an aminoglycoside antibiotic within 12 weeks or the need for this antibiotic or statin during study * Forced vital capacity % predicted \[FVC % predicted\] \<40%, or requiring daytime ventilation. * Require antiarrhythmic and/or antidiuretic therapy for heart failure. * Have a left ventricular ejection fraction (LVEF) of \<40%. * Prior or ongoing medical condition that could adversely affect the safety of the patient, make it unlikely that the course of treatment would be completed, or impair the assessment of study results.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment Emergent Adverse Events	From first dose of drug up to 100 weeks	An adverse event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. A 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 AEs 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 pretreatment state. AEs included both serious and non-serious adverse events.

Secondary

Measure	Time frame	Description
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities	Baseline up to 100 weeks	Laboratory parameters included hematology, clinical chemistry, urinalysis and coagulation. Data is only reported for parameters in which at least 1 participant had potentially clinically significant abnormal findings. Incr=increase; LLN=lower limit of normal; ULN=upper limit of normal; GGT=gamma glutamyl transferase
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Baseline up to 100 weeks	Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Data is only reported for parameters in which at least 1 participant had potentially clinically significant abnormal vital sign findings.
Number of Participants With at Least One Potentially Clinically Significant Abnormalities in Physical Examinations	Baseline up to 100 weeks	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. Brief physical examinations included examination of general appearance; head, ears, eyes, nose, and throat; heart; lungs; chest; abdomen; and skin.
Number of Participants With Abnormalities in Electrocardiograms (ECGs)	Baseline up to 100 weeks	Twelve-lead ECGs and Holter ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the patient 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 using a central vendor according to prespecified criteria. The Investigator reviewed the results of the centrally read ECG report and determined if the findings were clinically significant. Data is only reported for parameters in which at least 1 participant had potentially clinically significant abnormal ECG findings. msec=milliseconds; QTcF=QT interval corrected with Fridericia's method
Number of Participants With Abnormalities in Echocardiograms (ECHO)	Baseline up to 100 weeks	Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. The ECHO was reviewed and interpreted by medically qualified personnel using a central vendor according to prespecified criteria. Ejection fraction was noted. The Investigator reviewed the results of the ECHO report and determined if the findings were clinically significant. LEVF=left ventricular ejection fraction

Countries

United States

Participant flow

Pre-assignment details

The study was conducted at 9 sites in the United States from November 2014 to March 2018.

Participants by arm

Arm	Count
Eteplirsen 30 mg/kg Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.	24
Total	24

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal by Subject	2

Baseline characteristics

Characteristic	Eteplirsen 30 mg/kg
Age, Continuous	12.9 years STANDARD_DEVIATION 3.3
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	1 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	21 Participants
Region of Enrollment United States	24 participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	24 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 24
other Total, other adverse events	24 / 24
serious Total, serious adverse events	4 / 24

Outcome results

Primary

Number of Participants With Treatment Emergent Adverse Events

An adverse event (AE) was any untoward medical occurrence in a participant that did not necessarily have a causal relationship with the study drug. A 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 AEs 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 pretreatment state. AEs included both serious and non-serious adverse events.

Time frame: From first dose of drug up to 100 weeks

Population: Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Eteplirsen 30 mg/kg	Number of Participants With Treatment Emergent Adverse Events	24 Participants

Secondary

Number of Participants With Abnormalities in Echocardiograms (ECHO)

Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. The ECHO was reviewed and interpreted by medically qualified personnel using a central vendor according to prespecified criteria. Ejection fraction was noted. The Investigator reviewed the results of the ECHO report and determined if the findings were clinically significant. LEVF=left ventricular ejection fraction