Trial Outcomes & Findings for Safety Study of Eteplirsen to Treat Advanced Stage Duchenne Muscular Dystrophy (NCT NCT02286947)
NCT ID: NCT02286947
Last Updated: 2020-03-30
Results Overview
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.
COMPLETED
PHASE2
24 participants
From first dose of drug up to 100 weeks
2020-03-30
Participant Flow
The study was conducted at 9 sites in the United States from November 2014 to March 2018.
Participant milestones
| Measure |
Eteplirsen 30 mg/kg
Participants received eteplirsen 30 mg/kg intravenous (IV) infusions, once weekly, for 96 weeks.
|
|---|---|
|
Overall Study
STARTED
|
24
|
|
Overall Study
COMPLETED
|
22
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Eteplirsen 30 mg/kg
Participants received eteplirsen 30 mg/kg intravenous (IV) infusions, once weekly, for 96 weeks.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
Baseline Characteristics
Safety Study of Eteplirsen to Treat Advanced Stage Duchenne Muscular Dystrophy
Baseline characteristics by cohort
| Measure |
Eteplirsen 30 mg/kg
n=24 Participants
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
|
|---|---|
|
Age, Continuous
|
12.9 years
STANDARD_DEVIATION 3.30 • n=99 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
20 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
21 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: From first dose of drug up to 100 weeksPopulation: Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen.
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.
Outcome measures
| Measure |
Eteplirsen 30 mg/kg
n=24 Participants
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
|
|---|---|
|
Number of Participants With Treatment Emergent Adverse Events
|
24 Participants
|
SECONDARY outcome
Timeframe: Baseline up to 100 weeksPopulation: Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen.
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
Outcome measures
| Measure |
Eteplirsen 30 mg/kg
n=24 Participants
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
|
|---|---|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Sodium: Decrease of 8 or more
|
3 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Sodium: Increase of 8 or more
|
3 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Potassium: Decrease of 1.1 or more
|
2 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Potassium: Increase of 1.0 or more
|
2 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Potassium: Value > 5.5 or < 3.0
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Calcium: Decrease of 0.30 or more
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Glucose: Decrease of 3.1 or more
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Glucose: Increase of 3.2 or more
|
6 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Albumin: Value < LLN or > ULN
|
4 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Bilirubin: Incr of 10 or more
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Bilirubin: Value > 1.5 x ULN
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Alanine Aminotransferase: Value >= 2 x Baseline
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
GGT: value > 3*Baseline or > ULN
|
2 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Lactate Dehydrogenase: Value >= 2 x Baseline
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Creatine Kinase: Value >= 2 x Baseline
|
5 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Hemoglobin: Value < LLN
|
5 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Hematocrit: Value < LLN
|
7 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Red Blood Cell: Value < LLN
|
4 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
White Blood Cell: Value < LLN or > 1.5 x ULN
|
5 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Platelets: Value < 150 or < 200
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Neutrophils: Value > 1.5 x ULN or < 1000
|
7 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Lymphocytes: Value < LLN
|
6 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Monocytes: Value < LLN
|
14 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Eosinophils: Value > 1.5 x ULN or < LLN
|
2 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Basophils: Value < LLN or > ULN
|
2 Participants
|
|
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
Urine Protein: Value > 1+
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline up to 100 weeksPopulation: Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen.
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.
Outcome measures
| Measure |
Eteplirsen 30 mg/kg
n=24 Participants
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
|
|---|---|
|
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
DBP: Less than 40 mmHG
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
DBP: Greater than 90 mmHg
|
12 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
SBP: Less than 80 mmHg
|
4 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
SBP: Greater than 130 mmHG
|
17 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
HR: Less than 50 beats per minute (bpm)
|
1 Participants
|
|
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs
HR: Greater than 130 bpm
|
15 Participants
|
SECONDARY outcome
Timeframe: Baseline up to 100 weeksPhysical 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.
Outcome measures
| Measure |
Eteplirsen 30 mg/kg
n=24 Participants
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
|
|---|---|
|
Number of Participants With at Least One Potentially Clinically Significant Abnormalities in Physical Examinations
|
23 Participants
|
SECONDARY outcome
Timeframe: Baseline up to 100 weeksPopulation: Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen.
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
Outcome measures
| Measure |
Eteplirsen 30 mg/kg
n=24 Participants
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
|
|---|---|
|
Number of Participants With Abnormalities in Electrocardiograms (ECGs)
Heart Rate: >120 beats/minute
|
6 Participants
|
|
Number of Participants With Abnormalities in Electrocardiograms (ECGs)
QTcF: Increase of 60 or more msec
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline up to 100 weeksPopulation: Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen.
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
Outcome measures
| Measure |
Eteplirsen 30 mg/kg
n=24 Participants
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
|
|---|---|
|
Number of Participants With Abnormalities in Echocardiograms (ECHO)
LEVF: <55%
|
0 Participants
|
|
Number of Participants With Abnormalities in Echocardiograms (ECHO)
Fractional Shortening: <28%
|
6 Participants
|
Adverse Events
Eteplirsen 30 mg/kg
Serious adverse events
| Measure |
Eteplirsen 30 mg/kg
n=24 participants at risk
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Extremity contracture
|
4.2%
1/24 • Baseline up to Week 100
|
|
Musculoskeletal and connective tissue disorders
Scoliosis
|
4.2%
1/24 • Baseline up to Week 100
|
|
Cardiac disorders
Cardiomyopathy
|
4.2%
1/24 • Baseline up to Week 100
|
|
Renal and urinary disorders
Nephrolithiasis
|
4.2%
1/24 • Baseline up to Week 100
|
Other adverse events
| Measure |
Eteplirsen 30 mg/kg
n=24 participants at risk
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks.
|
|---|---|
|
Infections and infestations
Nasopharyngitis
|
58.3%
14/24 • Baseline up to Week 100
|
|
Infections and infestations
Upper respiratory tract infection
|
25.0%
6/24 • Baseline up to Week 100
|
|
Infections and infestations
Ear infection
|
12.5%
3/24 • Baseline up to Week 100
|
|
Infections and infestations
Gastroenteritis
|
12.5%
3/24 • Baseline up to Week 100
|
|
Infections and infestations
Pharyngitis streptococcal
|
12.5%
3/24 • Baseline up to Week 100
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
29.2%
7/24 • Baseline up to Week 100
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
20.8%
5/24 • Baseline up to Week 100
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
20.8%
5/24 • Baseline up to Week 100
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
20.8%
5/24 • Baseline up to Week 100
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
8.3%
2/24 • Baseline up to Week 100
|
|
Injury, poisoning and procedural complications
Contusion
|
25.0%
6/24 • Baseline up to Week 100
|
|
Injury, poisoning and procedural complications
Procedural pain
|
16.7%
4/24 • Baseline up to Week 100
|
|
Injury, poisoning and procedural complications
Joint injury
|
12.5%
3/24 • Baseline up to Week 100
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
12.5%
3/24 • Baseline up to Week 100
|
|
Injury, poisoning and procedural complications
Foot fracture
|
8.3%
2/24 • Baseline up to Week 100
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
8.3%
2/24 • Baseline up to Week 100
|
|
Injury, poisoning and procedural complications
Soft tissue injury
|
8.3%
2/24 • Baseline up to Week 100
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
8.3%
2/24 • Baseline up to Week 100
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
37.5%
9/24 • Baseline up to Week 100
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
16.7%
4/24 • Baseline up to Week 100
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.5%
3/24 • Baseline up to Week 100
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
8.3%
2/24 • Baseline up to Week 100
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
8.3%
2/24 • Baseline up to Week 100
|
|
Musculoskeletal and connective tissue disorders
Osteoporosis
|
8.3%
2/24 • Baseline up to Week 100
|
|
Gastrointestinal disorders
Vomiting
|
29.2%
7/24 • Baseline up to Week 100
|
|
Gastrointestinal disorders
Abdominal pain upper
|
25.0%
6/24 • Baseline up to Week 100
|
|
Gastrointestinal disorders
Diarrhoea
|
25.0%
6/24 • Baseline up to Week 100
|
|
Gastrointestinal disorders
Nausea
|
16.7%
4/24 • Baseline up to Week 100
|
|
Gastrointestinal disorders
Abdominal discomfort
|
12.5%
3/24 • Baseline up to Week 100
|
|
Gastrointestinal disorders
Constipation
|
12.5%
3/24 • Baseline up to Week 100
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
8/24 • Baseline up to Week 100
|
|
Skin and subcutaneous tissue disorders
Acne
|
8.3%
2/24 • Baseline up to Week 100
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
8.3%
2/24 • Baseline up to Week 100
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
8.3%
2/24 • Baseline up to Week 100
|
|
General disorders
Catheter site pain
|
20.8%
5/24 • Baseline up to Week 100
|
|
General disorders
Infusion site bruising
|
16.7%
4/24 • Baseline up to Week 100
|
|
General disorders
Catheter site bruise
|
12.5%
3/24 • Baseline up to Week 100
|
|
General disorders
Pyrexia
|
12.5%
3/24 • Baseline up to Week 100
|
|
General disorders
Chest pain
|
8.3%
2/24 • Baseline up to Week 100
|
|
General disorders
Infusion site pain
|
8.3%
2/24 • Baseline up to Week 100
|
|
Nervous system disorders
Headache
|
33.3%
8/24 • Baseline up to Week 100
|
|
Nervous system disorders
Dizziness
|
8.3%
2/24 • Baseline up to Week 100
|
|
Investigations
Breath sounds abnormal
|
12.5%
3/24 • Baseline up to Week 100
|
|
Investigations
Protein urine present
|
8.3%
2/24 • Baseline up to Week 100
|
|
Metabolism and nutrition disorders
Dehydration
|
8.3%
2/24 • Baseline up to Week 100
|
|
Psychiatric disorders
Depression
|
8.3%
2/24 • Baseline up to Week 100
|
|
Renal and urinary disorders
Renal pain
|
8.3%
2/24 • Baseline up to Week 100
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The most restrictive relevant agreement provides that the PI can only publish the study results with the approval of Sponsor.
- Publication restrictions are in place
Restriction type: OTHER