Clinical Trial Results:
An Open-Label, Multi-Center Study to Evaluate the Safety and Tolerability of Eteplirsen in Patients With Advanced Stage Duchenne Muscular Dystrophy
Summary
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EudraCT number |
2016-005024-28 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
23 Mar 2018
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Results information
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Results version number |
v2(current) |
This version publication date |
31 Jul 2019
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First version publication date |
28 Mar 2019
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
4658-204
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02286947 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
4658-204: Study Number | ||
Sponsors
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Sponsor organisation name |
Sarepta Therapeutics, Inc.
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Sponsor organisation address |
215 First Street, Cambridge, United States, 02142
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Public contact |
Medical Director, Sarepta Therapeutics, Inc., +1 888-727-3782, clinicaltrials@sarepta.com
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Scientific contact |
Medical Director, Sarepta Therapeutics, Inc., +1 888-727-3782, clinicaltrials@sarepta.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-001722-PIP01-14 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Oct 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Mar 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To explore safety and tolerability of eteplirsen in patients with advanced stage Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping.
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Protection of trial subjects |
Written informed consent from each patient or patient’s parent(s) or legal guardian(s), if applicable, and written assent from each patient, if applicable, were obtained before any study-specific screening or baseline period evaluations were performed. The anonymity of participating patients will be maintained to the extent required by applicable laws and in accordance with current HIPAA standards. This study was designed and monitored in accordance with Sponsor procedures, which complied with the ethical principles of Good Clinical Practice (GCP) as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Nov 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 24
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Worldwide total number of subjects |
24
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
9
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Adolescents (12-17 years) |
12
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Adults (18-64 years) |
3
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
Pre-assignment
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Screening details |
The study was conducted at 9 sites in the United States from November 2014 to March 2018. | ||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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Eteplirsen 30 mg/kg | ||||||||||
Arm description |
Subjects received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusion, once weekly, for 96 weeks. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Eteplirsen
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received eteplirsen 30 mg/kg IV infusion once weekly.
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Baseline characteristics reporting groups
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Reporting group title |
Eteplirsen 30 mg/kg
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Reporting group description |
Subjects received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusion, once weekly, for 96 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Eteplirsen 30 mg/kg
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Reporting group description |
Subjects received eteplirsen 30 milligram per kilogram (mg/kg) intravenous (IV) infusion, once weekly, for 96 weeks. |
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End point title |
Number of Subjects With Treatment Emergent Adverse Events [1] | ||||||
End point description |
An AE was any untoward medical occurrence in a subject that did not necessarily have a causal relationship with the study drug. An 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. Analysis was performed on safety population which included all subjects who received at least 1 dose of eteplirsen.
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End point type |
Primary
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End point timeframe |
From first dose of drug up to 100 weeks
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis not applicable for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Potentially Clinically Significant Laboratory Abnormalities | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Laboratory parameters included hematology, clinical chemistry, urinalysis and coagulation. Data is only reported for parameters in which at least 1 subject had potentially clinically significant abnormal
findings. Analysis was performed on safety population which included all subjects who received at least 1 dose of eteplirsen.
Incr=increase; LLN=lower limit of normal; ULN=upper limit of normal; GGT=gamma glutamyl transferase
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End point type |
Secondary
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End point timeframe |
Baseline up to 100 weeks
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Potentially Clinically Significant Abnormalities in Vital Signs | ||||||||||||||||||
End point description |
Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP) in millimeters of mercury (mmHg), heart rate (HR), and body temperature. Data is only reported for parameters in which at least 1 subject had potentially clinically significant abnormal vital sign findings. Analysis was performed on safety population which included all subjects who received at least 1 dose of eteplirsen.
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End point type |
Secondary
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End point timeframe |
Baseline up to 100 weeks
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No statistical analyses for this end point |
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End point title |
Number of Subjects With at Least One Abnormal Physical Examination Finding | ||||||
End point description |
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. Analysis was performed on safety population which included all subjects who received at least 1 dose of eteplirsen.
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End point type |
Secondary
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End point timeframe |
Baseline up to 100 weeks
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Abnormalities in Electrocardiograms (ECGs) | ||||||||||
End point description |
Twelve-lead ECGs and Holter ECGs were performed at a consistent time of day throughout the study. ECGs were performed only after the subject 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 subject had potentially clinically significant abnormal ECG findings. Analysis was performed on safety population which included all subjects who received at least 1 dose of eteplirsen.
msec=milliseconds; QTcF=QT interval corrected with Fridericia’s method
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End point type |
Secondary
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End point timeframe |
Baseline up to 100 weeks
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Abnormalities in Echocardiograms (ECHO) | ||||||||||
End point description |
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. Analysis was performed on safety population included which all subjects who received at least 1 dose of eteplirsen.
LEVF=left ventricular ejection fraction
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End point type |
Secondary
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End point timeframe |
Baseline up to 100 weeks
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to Week 100
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Adverse event reporting additional description |
Safety population included all subjects who received at least 1 dose of eteplirsen.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Eteplirsen 30 mg/kg
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Reporting group description |
Subjects received eteplirsen 30 mg/kg, IV infusions, once weekly, for 96 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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30 Jun 2014 |
The overall reason for the amendment was to add a safety extension period to allow continued treatment with eteplirsen for an additional 48 weeks. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |