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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eteplirsen 30 mg/kg | Experimental | Participants will receive eteplirsen 30 mg/kg/week intravenous (IV) infusions, weekly, for up to 96 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eteplirsen | Drug | Eteplirsen solution for IV infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From first dose of drug up to 100 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Potentially Clinically Significant Laboratory Abnormalities | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Sarepta Therapeutics, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ronald Reagan UCLA Medical Center | Los Angeles | California | 90095 | United States | ||
| University of California, Davis Medical Center |
The study was conducted at 9 sites in the United States from November 2014 to March 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | Eteplirsen 30 mg/kg | Participants received eteplirsen 30 mg/kg intravenous (IV) infusions, once weekly, for 96 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety analysis population included all enrolled participants who received at least 1 dose of eteplirsen.
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| ID | Title | Description |
|---|---|---|
| BG000 | Eteplirsen 30 mg/kg | Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen. | Posted | Count of Participants | Participants | From first dose of drug up to 100 weeks |
|
Baseline up to Week 100
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Eteplirsen 30 mg/kg | Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Extremity contracture | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA 17.1 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Sarepta Therapeutics, Inc. | +1-888-727-3782 | clinicaltrials@sarepta.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 5, 2016 | Jan 30, 2019 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 20, 2017 | Jan 30, 2019 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D020388 | Muscular Dystrophy, Duchenne |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| C000611335 | eteplirsen |
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| Baseline up to 100 weeks |
| Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs | 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. | Baseline up to 100 weeks |
| Number of Participants With at Least One Potentially Clinically Significant Abnormalities in Physical Examinations | 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. | Baseline up to 100 weeks |
| Number of Participants With Abnormalities in Electrocardiograms (ECGs) | 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 | Baseline up to 100 weeks |
| 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 | Baseline up to 100 weeks |
| Sacramento |
| California |
| 95817 |
| United States |
| University of Iowa Children's Hospital | Iowa City | Iowa | 52242 | United States |
| Kennedy Krieger Institute | Baltimore | Maryland | 21205 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| St. Louis Children's Hospital | St Louis | Missouri | 63110 | United States |
| University of Rochester Medical Center | Rochester | New York | 14642 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205 | United States |
| Seattle Children's Hospital | Seattle | Washington | 98105 | United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Eteplirsen 30 mg/kg |
Participants received eteplirsen 30 mg/kg IV infusions, weekly, for 96 weeks. |
|
|
| Secondary | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities | 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 | Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen. | Posted | Count of Participants | Participants | Baseline up to 100 weeks |
|
|
|
| Secondary | Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs | 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. | Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen. | Posted | Count of Participants | Participants | Baseline up to 100 weeks |
|
|
|
| Secondary | Number of Participants With at Least One Potentially Clinically Significant Abnormalities in Physical Examinations | 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. | Posted | Count of Participants | Participants | Baseline up to 100 weeks |
|
|
|
| Secondary | Number of Participants With Abnormalities in Electrocardiograms (ECGs) | 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 | Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen. | Posted | Count of Participants | Participants | Baseline up to 100 weeks |
|
|
|
| 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 | Analysis was performed on safety population included all participants who received at least 1 dose of eteplirsen. | Posted | Count of Participants | Participants | Baseline up to 100 weeks |
|
|
|
| 0 |
| 24 |
| 4 |
| 24 |
| 24 |
| 24 |
| Scoliosis | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Cardiomyopathy | Cardiac disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 17.1 | Non-systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA 17.1 | Non-systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 17.1 | Non-systematic Assessment |
|
| Pharyngitis streptococcal | Infections and infestations | MedDRA 17.1 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
|
| Joint injury | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
|
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
|
| Foot fracture | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
|
| Soft tissue injury | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
|
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 17.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Infusion site bruising | General disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Catheter site bruise | General disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Infusion site pain | General disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Breath sounds abnormal | Investigations | MedDRA 17.1 | Non-systematic Assessment |
|
| Protein urine present | Investigations | MedDRA 17.1 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 17.1 | Non-systematic Assessment |
|
| Renal pain | Renal and urinary disorders | MedDRA 17.1 | Non-systematic Assessment |
|
The most restrictive relevant agreement provides that the PI can only publish the study results with the approval of Sponsor.
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| Title | Measurements |
|---|---|
|
| Potassium: Increase of 1.0 or more |
|
| Potassium: Value > 5.5 or < 3.0 |
|
| Calcium: Decrease of 0.30 or more |
|
| Glucose: Decrease of 3.1 or more |
|
| Glucose: Increase of 3.2 or more |
|
| Albumin: Value < LLN or > ULN |
|
| Bilirubin: Incr of 10 or more |
|
| Bilirubin: Value > 1.5 x ULN |
|
| Alanine Aminotransferase: Value >= 2 x Baseline |
|
| GGT: value > 3*Baseline or > ULN |
|
| Lactate Dehydrogenase: Value >= 2 x Baseline |
|
| Creatine Kinase: Value >= 2 x Baseline |
|
| Hemoglobin: Value < LLN |
|
| Hematocrit: Value < LLN |
|
| Red Blood Cell: Value < LLN |
|
| White Blood Cell: Value < LLN or > 1.5 x ULN |
|
| Platelets: Value < 150 or < 200 |
|
| Neutrophils: Value > 1.5 x ULN or < 1000 |
|
| Lymphocytes: Value < LLN |
|
| Monocytes: Value < LLN |
|
| Eosinophils: Value > 1.5 x ULN or < LLN |
|
| Basophils: Value < LLN or > ULN |
|
| Urine Protein: Value > 1+ |
|
| Title | Measurements |
|---|---|
|
| SBP: Greater than 130 mmHG |
|
| HR: Less than 50 beats per minute (bpm) |
|
| HR: Greater than 130 bpm |
|