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Safety Study of Eteplirsen to Treat Advanced Stage Duchenne Muscular Dystrophy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02286947
Recruitment Status : Completed
First Posted : November 10, 2014
Results First Posted : February 20, 2019
Last Update Posted : May 7, 2019
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Muscular Dystrophy, Duchenne
Intervention Drug: Eteplirsen
Enrollment 24
Recruitment Details  
Pre-assignment Details The study was conducted at 9 sites in the United States from November 2014 to March 2018.
Arm/Group Title Eteplirsen 30 mg/kg
Hide Arm/Group Description Participants received eteplirsen 30 mg/kg intravenous (IV) infusions, once weekly, for 96 weeks.
Period Title: Overall Study
Started 24
Completed 22
Not Completed 2
Reason Not Completed
Withdrawal by Subject             2
Arm/Group Title Eteplirsen 30 mg/kg
Hide Arm/Group Description Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
Overall Number of Baseline Participants 24
Hide Baseline Analysis Population Description
Safety analysis population included all enrolled participants who received at least 1 dose of eteplirsen.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants
12.9  (3.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Female
0
   0.0%
Male
24
 100.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
Hispanic or Latino
3
  12.5%
Not Hispanic or Latino
20
  83.3%
Unknown or Not Reported
1
   4.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants
American Indian or Alaska Native
0
   0.0%
Asian
1
   4.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
21
  87.5%
More than one race
2
   8.3%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 24 participants
24
1.Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen.
Arm/Group Title Eteplirsen 30 mg/kg
Hide Arm/Group Description:
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
24
 100.0%
2.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Hide Description

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

Time Frame Baseline up to 100 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen.
Arm/Group Title Eteplirsen 30 mg/kg
Hide Arm/Group Description:
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
Sodium: Decrease of 8 or more
3
  12.5%
Sodium: Increase of 8 or more
3
  12.5%
Potassium: Decrease of 1.1 or more
2
   8.3%
Potassium: Increase of 1.0 or more
2
   8.3%
Potassium: Value > 5.5 or < 3.0
1
   4.2%
Calcium: Decrease of 0.30 or more
1
   4.2%
Glucose: Decrease of 3.1 or more
1
   4.2%
Glucose: Increase of 3.2 or more
6
  25.0%
Albumin: Value < LLN or > ULN
4
  16.7%
Bilirubin: Incr of 10 or more
1
   4.2%
Bilirubin: Value > 1.5 x ULN
1
   4.2%
Alanine Aminotransferase: Value >= 2 x Baseline
1
   4.2%
GGT: value > 3*Baseline or > ULN
2
   8.3%
Lactate Dehydrogenase: Value >= 2 x Baseline
1
   4.2%
Creatine Kinase: Value >= 2 x Baseline
5
  20.8%
Hemoglobin: Value < LLN
5
  20.8%
Hematocrit: Value < LLN
7
  29.2%
Red Blood Cell: Value < LLN
4
  16.7%
White Blood Cell: Value < LLN or > 1.5 x ULN
5
  20.8%
Platelets: Value < 150 or < 200
1
   4.2%
Neutrophils: Value > 1.5 x ULN or < 1000
7
  29.2%
Lymphocytes: Value < LLN
6
  25.0%
Monocytes: Value < LLN
14
  58.3%
Eosinophils: Value > 1.5 x ULN or < LLN
2
   8.3%
Basophils: Value < LLN or > ULN
2
   8.3%
Urine Protein: Value > 1+
5
  20.8%
3.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
Hide Description 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.
Time Frame Baseline up to 100 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen.
Arm/Group Title Eteplirsen 30 mg/kg
Hide Arm/Group Description:
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
DBP: Less than 40 mmHG
1
   4.2%
DBP: Greater than 90 mmHg
12
  50.0%
SBP: Less than 80 mmHg
4
  16.7%
SBP: Greater than 130 mmHG
17
  70.8%
HR: Less than 50 beats per minute (bpm)
1
   4.2%
HR: Greater than 130 bpm
15
  62.5%
4.Secondary Outcome
Title Number of Participants With at Least One Potentially Clinically Significant Abnormalities in Physical Examinations
Hide 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.
Time Frame Baseline up to 100 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Eteplirsen 30 mg/kg
Hide Arm/Group Description:
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
23
  95.8%
5.Secondary Outcome
Title Number of Participants With Abnormalities in Electrocardiograms (ECGs)
Hide Description

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

Time Frame Baseline up to 100 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen.
Arm/Group Title Eteplirsen 30 mg/kg
Hide Arm/Group Description:
Participants received eteplirsen 30 mg/kg intravenous (IV) infusions, weekly, for 96 weeks.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
Heart Rate: >120 beats/minute
6
  25.0%
QTcF: Increase of 60 or more msec
1
   4.2%
6.Secondary Outcome
Title Number of Participants With Abnormalities in Echocardiograms (ECHO)
Hide 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.

LEVF=left ventricular ejection fraction

Time Frame Baseline up to 100 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen.
Arm/Group Title Eteplirsen 30 mg/kg
Hide Arm/Group Description:
Participants received eteplirsen 30 mg/kg intravenous (IV) infusions, once weekly, for 96 weeks.
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
LEVF: <55%
0
   0.0%
Fractional Shortening: <28%
6
  25.0%
Time Frame Baseline up to Week 100
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Eteplirsen 30 mg/kg
Hide Arm/Group Description Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
All-Cause Mortality
Eteplirsen 30 mg/kg
Affected / at Risk (%)
Total   0/24 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Eteplirsen 30 mg/kg
Affected / at Risk (%)
Total   4/24 (16.67%) 
Cardiac disorders   
Cardiomyopathy * 1  1/24 (4.17%) 
Musculoskeletal and connective tissue disorders   
Extremity contracture * 1  1/24 (4.17%) 
Scoliosis * 1  1/24 (4.17%) 
Renal and urinary disorders   
Nephrolithiasis * 1  1/24 (4.17%) 
1
Term from vocabulary, MedDRA 17.1
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Eteplirsen 30 mg/kg
Affected / at Risk (%)
Total   24/24 (100.00%) 
Gastrointestinal disorders   
Vomiting * 1  7/24 (29.17%) 
Abdominal pain upper * 1  6/24 (25.00%) 
Diarrhoea * 1  6/24 (25.00%) 
Nausea * 1  4/24 (16.67%) 
Abdominal discomfort * 1  3/24 (12.50%) 
Constipation * 1  3/24 (12.50%) 
General disorders   
Catheter site pain * 1  5/24 (20.83%) 
Infusion site bruising * 1  4/24 (16.67%) 
Catheter site bruise * 1  3/24 (12.50%) 
Pyrexia * 1  3/24 (12.50%) 
Chest pain * 1  2/24 (8.33%) 
Infusion site pain * 1  2/24 (8.33%) 
Infections and infestations   
Nasopharyngitis * 1  14/24 (58.33%) 
Upper respiratory tract infection * 1  6/24 (25.00%) 
Ear infection * 1  3/24 (12.50%) 
Gastroenteritis * 1  3/24 (12.50%) 
Pharyngitis streptococcal * 1  3/24 (12.50%) 
Injury, poisoning and procedural complications   
Contusion * 1  6/24 (25.00%) 
Procedural pain * 1  4/24 (16.67%) 
Joint injury * 1  3/24 (12.50%) 
Ligament sprain * 1  3/24 (12.50%) 
Foot fracture * 1  2/24 (8.33%) 
Skin abrasion * 1  2/24 (8.33%) 
Soft tissue injury * 1  2/24 (8.33%) 
Spinal compression fracture * 1  2/24 (8.33%) 
Investigations   
Breath sounds abnormal * 1  3/24 (12.50%) 
Protein urine present * 1  2/24 (8.33%) 
Metabolism and nutrition disorders   
Dehydration * 1  2/24 (8.33%) 
Musculoskeletal and connective tissue disorders   
Back pain * 1  9/24 (37.50%) 
Pain in extremity * 1  4/24 (16.67%) 
Arthralgia * 1  3/24 (12.50%) 
Muscle spasms * 1  2/24 (8.33%) 
Musculoskeletal pain * 1  2/24 (8.33%) 
Osteoporosis * 1  2/24 (8.33%) 
Nervous system disorders   
Headache * 1  8/24 (33.33%) 
Dizziness * 1  2/24 (8.33%) 
Psychiatric disorders   
Depression * 1  2/24 (8.33%) 
Renal and urinary disorders   
Renal pain * 1  2/24 (8.33%) 
Respiratory, thoracic and mediastinal disorders   
Cough * 1  7/24 (29.17%) 
Nasal congestion * 1  5/24 (20.83%) 
Oropharyngeal pain * 1  5/24 (20.83%) 
Rhinorrhoea * 1  5/24 (20.83%) 
Throat irritation * 1  2/24 (8.33%) 
Skin and subcutaneous tissue disorders   
Rash * 1  8/24 (33.33%) 
Acne * 1  2/24 (8.33%) 
Ecchymosis * 1  2/24 (8.33%) 
Rash papular * 1  2/24 (8.33%) 
1
Term from vocabulary, MedDRA 17.1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The most restrictive relevant agreement provides that the PI can only publish the study results with the approval of Sponsor.
Results Point of Contact
Name/Title: Medical Director
Organization: Sarepta Therapeutics, Inc.
Phone: 617 274-4000
Responsible Party: Sarepta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02286947     History of Changes
Other Study ID Numbers: 4658-204
First Submitted: October 30, 2014
First Posted: November 10, 2014
Results First Submitted: January 30, 2019
Results First Posted: February 20, 2019
Last Update Posted: May 7, 2019