Back to resultsPhase I/II Study of SRP-4053 in DMD Patients
Primary Purpose
Duchenne Muscular Dystrophy
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Placebo
SRP-4053
Sponsored by
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy focused on measuring Duchenne muscular dystrophy, Exon Skipping, DMD, Exon 53, Ambulatory, Pediatric
Eligibility Criteria
Inclusion Criteria:
- Diagnosed with DMD, genotypically confirmed.
- Intact right and left biceps muscles or an alternative upper arm muscle group.
- Stable pulmonary and cardiac function.
- Minimum performance on 6MWT, North Star Ambulatory Assessment, and rise (Gowers) test as specified in the study protocol.
- On a stable dose of corticosteroids for at least 6 months.
Exclusion Criteria:
- Previous treatment with the experimental agents BMN-195 (SMT C1100) or PRO053.
- Current or previous treatment with any other experimental treatments within 12 weeks prior to study entry.
- Major surgery within the last 3 months.
- Presence of other clinically significant illness.
- Major change in physical therapy regime within the last 3 months.
Other inclusion and exclusion criteria may apply.
Sites / Locations
- Boston Children's Hospital
- Institute de Myologie
- Policlinico Universitario A Gemelli
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Newcastle University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Placebo Comparator
Experimental
No Intervention
Arm Label
Part 1: SRP-4053
Part 1: Placebo
Part 2: SRP-4053
Part 2: Untreated Group
Arm Description
Patients will receive SRP-4053 (golodirsen) intravenous (IV) infusions, weekly, at escalating dose levels as follows: Weeks 1-2, 4 mg/kg/week; Weeks 3-4, 10 mg/kg/week; Weeks 5-6, 20 mg/kg/week; Weeks 7-12, 30 mg/kg/week. Dosing will be interrupted or halted if specific predefined stopping criteria are met or if warranted at the discretion of the Sponsor or Investigator.
Patients will receive SRP-4053 placebo-matching IV infusions, weekly, for 12 weeks. Dosing will be interrupted or halted if specific predefined stopping criteria are met or if warranted at the discretion of the Sponsor or Investigator.
All eligible patients from Part 1, as well as new patients, will receive SRP-4053 (golodirsen) 30 mg/kg/week IV infusions, weekly, for up to 168 weeks.
Patients with DMD who have a genotypically confirmed deletion of exon(s) not amenable to treatment by exon 53 skipping, but who otherwise meet the same eligibility criteria as treated patients newly recruited to Part 2, will undergo the same study assessments as treated Patients (except for pharmacokinetic [PK] sampling and muscle biopsies), but at a reduced schedule through Week 144. The untreated patients are not considered as control group.
Outcomes
Primary Outcome Measures
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Discontinuation
Adverse event (AE) was any untoward medical occurrence in a clinical trial participant, which does not necessarily have a causal relationship with the investigational 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. TEAEs were defined as AEs that were reported or worsened on or after the start of study drug dosing through 12 weeks. TEAEs included both Serious TEAEs and non-serious TEAEs.
Part 1: Number of Participants With Potentially Clinically Significant (PCS) Laboratory Abnormalities Reported as TEAEs
Laboratory parameters included hematology, serum chemistry (SC), urinalysis and coagulation. Number of participants with at least one potentially clinically significant abnormal finding were reported as TEAEs. The Investigator determined whether abnormal assessment results were potentially clinically significant or not. Potentially clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs
Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Number of participants with at least one potentially clinically significant abnormal vital signs findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were potentially clinically significant or not. Potential clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Physical Examinations
Physical examinations were performed by the Investigator, or qualified study staff. A full physical examination included a review of general appearance, head, eyes, ears, nose and throat, heart, lungs, abdomen, extremities, skin, lymph nodes, musculoskeletal, and neurological systems. Number of participants with potentially clinically significant abnormalities in physical examinations were reported. Potentially clinically significant abnormalities in physical examinations were based on Investigator's discretion.
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Reported as TEAEs
Twelve-lead ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the participant 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. Number of participants with potentially clinically significant abnormalities in ECG reported as TEAEs presented here. The Investigator determined whether abnormal assessment results were potentially clinically significant or not.
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Echocardiograms (ECHO)
Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. Cardiac function events included cardiomegaly, tachycardia, and dyspnoea. The ECHO was reviewed and interpreted by medically qualified personnel. Number of participants with potentially clinically significant abnormalities in ECHO were reported.
Part 2a: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 144 in Total Golodirsen Group
6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course of 25 meters for 6 minutes (timed), and the distance walked (in meters) was recorded. Change from baseline in 6MWT distance at Week 144 in total golodirsen group was reported.
Part 2b: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 144 in Untreated Group (Non-exon 53 Amenable Participants)
6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course of 25 meters for 6 minutes (timed), and the distance walked (in meters) was recorded. Change from baseline in 6MWT distance at Week 144 in untreated group (non-exon 53 amenable participants) was calculated.
Part 2a: Change From Baseline in Dystrophin Protein Levels Determined by Western Blot at Week 48 in Total Golodirsen Group
Change from baseline in dystrophin protein levels (in muscle biopsy samples) was determined by Western blot in total golodirsen group.
Secondary Outcome Measures
Part 1: Maximum Plasma Concentration (Cmax) of Golodirsen
Maximum Concentration (Cmax) of golodirsen in plasma was evaluated.
Part 1: Time to Reach Maximum Plasma Concentration (Tmax) of Golodirsen
Time to reach maximum plasma concentration (Tmax) of golodirsen was evaluated.
Part 1: Area Under the Concentration-Time Curve From Time Zero Extrapolated to the Infinity (AUCinf) of Golodirsen in Plasma
Area under the concentration-time curve from time zero extrapolated to the infinity was evaluated.
Part 1: Apparent Volume of Distribution at Steady State (Vss) of Golodirsen
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution at steady state of golodirsen was evaluated.
Part 1: Elimination Half-life (T1/2) of Golodirsen
T1/2 is the time measured for the plasma concentration of drug to decrease by one half. T1/2 of golodirsen was evaluated.
Part 1: Total Clearance (CL) of Golodirsen
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Part 1: Mean Residence Time (MRT) of Golodirsen
MRT= AUMCinf/AUCinf, where AUMCinf is the area under the first moment curve from time 0 extrapolated to infinite time, calculated using the linear/log trapezoidal method. Mean residence time of golodirsen was evaluated.
Part 1: Renal Clearance (CLR) of Golodirsen
Renal clearance was calculated using the partial AUC0-24 from the non-compartmental analysis in plasma and AE0-24. AUC0-24 was defined as area under the plasma concentration-time curve, from time 0 to 24 hours after completion of dosing. AE0-24 was defined as total cumulative amount excreted from 0 to 24 hours. Summarized data of all urine collection intervals are reported.
Part 2a: Percent Change From Baseline in Forced Vital Capacity Predicted (FVC%p) at Week144 in Total Golodirsen Group
FVC was the total amount of air exhaled during the forced expiratory volume test that was measured during spirometry and the most important measurement of lung function. This test required participant to breath into a tube connected to a machine that measures the amount of air that can be moved in and out of the lungs after taking an inhaled bronchodilator medicine which was used to dilate participant bronchial (breathing) tubes. Percent of predicted FVC = (observed value)/ (predicted value) * 100%.
Part 2b: Percent Change From Baseline in Forced Vital Capacity Predicted (FVC%p) at Week144 in Untreated Group (Non-exon 53 Amenable Participants)
FVC was the total amount of air exhaled during the forced expiratory volume test that was measured during spirometry and is the most important measurement of lung function. This test requires participant to breath into a tube connected to a machine that measures the amount of air that can be moved in and out of the lungs after taking an inhaled bronchodilator medicine which was used to dilate participant bronchial (breathing) tubes. Percent of predicted FVC = (observed value)/ (predicted value) * 100%.
Part 2a: Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 in Total Golodirsen Group
Change from baseline in dystrophin Intensity levels (in muscle biopsy samples) was determined by Immunohistochemistry in total golodirsen group.
Part 2a: Percent Change From Baseline in Exon 53 Skipping Determined by Reverse Transcription Polymerase Chain Reaction (PCR) at Week 48 in Total Golodirsen Group
Percent change from baseline in Exon 53 skipping (in muscle biopsy samples) was determined by reverse transcription polymerase chain reaction in total golodirsen group.
Part 2a: Percent Change From Baseline in Dystrophin Positive Fibers Determined by Immunohistochemistry (IHC) at Week 48 in Total Golodirsen Group
Percent change from baseline in dystrophin positive fibers (in muscle biopsy samples) were determined by Immunohistochemistry at Week 48 in total golodirsen group.
Full Information
NCT ID
NCT02310906
First Posted
December 3, 2014
Last Updated
October 14, 2020
Sponsor
Sarepta Therapeutics, Inc.
Collaborators
Institut de Myologie, France, Consultants for Research in Imaging and Spectroscopy, Great Ormond Street Hospital for Children NHS Foundation Trust, Catholic University of the Sacred Heart, Royal Holloway University, Sysnav, University College, London, University of Newcastle Upon-Tyne
1. Study Identification
Unique Protocol Identification Number
NCT02310906
Brief Title
Phase I/II Study of SRP-4053 in DMD Patients
Official Title
A 2-Part, Randomized, Double-Blind, Placebo-Controlled, Dose-Titration, Safety, Tolerability, and Pharmacokinetics Study (Part 1) Followed by an Open-Label Efficacy and Safety Evaluation (Part 2) of SRP-4053 in Patients With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
January 13, 2015 (Actual)
Primary Completion Date
March 25, 2019 (Actual)
Study Completion Date
March 25, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sarepta Therapeutics, Inc.
Collaborators
Institut de Myologie, France, Consultants for Research in Imaging and Spectroscopy, Great Ormond Street Hospital for Children NHS Foundation Trust, Catholic University of the Sacred Heart, Royal Holloway University, Sysnav, University College, London, University of Newcastle Upon-Tyne
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a first-in-human, multiple-dose 2-part study to assess the safety, tolerability, efficacy, and pharmacokinetics of SRP-4053 in Duchenne muscular dystrophy (DMD) patients with deletions amenable to exon 53 skipping.
Detailed Description
Part 1: Randomized, placebo-controlled dose-titration to assess safety, tolerability and pharmacokinetics of 4 dose levels of SRP-4053 in genotypically-confirmed DMD patients with deletions amenable to exon 53 skipping.
Part 2: Open-label evaluation of SRP-4053 in patients from Part 1, along with newly enrolled DMD patients with deletions amenable to exon 53 skipping and an untreated group of DMD patients with deletions not amenable to exon 53 skipping.
Safety, including adverse event monitoring and routine laboratory assessments, will be followed on an ongoing basis for all patients.
Clinical efficacy, including functional tests such as the six-minute walk test (6MWT), will be assessed at regularly scheduled study visits. Patients in the treated groups will undergo one baseline and one follow-up muscle biopsy. Patients in the untreated group will not undergo biopsies and will follow an abbreviated schedule of study assessments.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy
Keywords
Duchenne muscular dystrophy, Exon Skipping, DMD, Exon 53, Ambulatory, Pediatric
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Masking Description: Part 1 is double-blind and randomized; Part 2 is open-label.
Allocation
Randomized
Enrollment
39 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1: SRP-4053
Arm Type
Experimental
Arm Description
Patients will receive SRP-4053 (golodirsen) intravenous (IV) infusions, weekly, at escalating dose levels as follows: Weeks 1-2, 4 mg/kg/week; Weeks 3-4, 10 mg/kg/week; Weeks 5-6, 20 mg/kg/week; Weeks 7-12, 30 mg/kg/week. Dosing will be interrupted or halted if specific predefined stopping criteria are met or if warranted at the discretion of the Sponsor or Investigator.
Arm Title
Part 1: Placebo
Arm Type
Placebo Comparator
Arm Description
Patients will receive SRP-4053 placebo-matching IV infusions, weekly, for 12 weeks. Dosing will be interrupted or halted if specific predefined stopping criteria are met or if warranted at the discretion of the Sponsor or Investigator.
Arm Title
Part 2: SRP-4053
Arm Type
Experimental
Arm Description
All eligible patients from Part 1, as well as new patients, will receive SRP-4053 (golodirsen) 30 mg/kg/week IV infusions, weekly, for up to 168 weeks.
Arm Title
Part 2: Untreated Group
Arm Type
No Intervention
Arm Description
Patients with DMD who have a genotypically confirmed deletion of exon(s) not amenable to treatment by exon 53 skipping, but who otherwise meet the same eligibility criteria as treated patients newly recruited to Part 2, will undergo the same study assessments as treated Patients (except for pharmacokinetic [PK] sampling and muscle biopsies), but at a reduced schedule through Week 144. The untreated patients are not considered as control group.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
SRP-4053 placebo-matching solution for IV infusion.
Intervention Type
Drug
Intervention Name(s)
SRP-4053
Intervention Description
SRP-4053 (golodirsen) solution for IV infusion.
Primary Outcome Measure Information:
Title
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Discontinuation
Description
Adverse event (AE) was any untoward medical occurrence in a clinical trial participant, which does not necessarily have a causal relationship with the investigational 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. TEAEs were defined as AEs that were reported or worsened on or after the start of study drug dosing through 12 weeks. TEAEs included both Serious TEAEs and non-serious TEAEs.
Time Frame
Baseline up to Week 12
Title
Part 1: Number of Participants With Potentially Clinically Significant (PCS) Laboratory Abnormalities Reported as TEAEs
Description
Laboratory parameters included hematology, serum chemistry (SC), urinalysis and coagulation. Number of participants with at least one potentially clinically significant abnormal finding were reported as TEAEs. The Investigator determined whether abnormal assessment results were potentially clinically significant or not. Potentially clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Time Frame
Baseline up to Week 12
Title
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs
Description
Vital sign parameters included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and body temperature. Number of participants with at least one potentially clinically significant abnormal vital signs findings were reported as TEAEs. The Investigator determined whether abnormal assessment results were potentially clinically significant or not. Potential clinical significance was defined as any variation in assessment results that had medical relevance resulting in an alteration in medical care.
Time Frame
Baseline up to Week 12
Title
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Physical Examinations
Description
Physical examinations were performed by the Investigator, or qualified study staff. A full physical examination included a review of general appearance, head, eyes, ears, nose and throat, heart, lungs, abdomen, extremities, skin, lymph nodes, musculoskeletal, and neurological systems. Number of participants with potentially clinically significant abnormalities in physical examinations were reported. Potentially clinically significant abnormalities in physical examinations were based on Investigator's discretion.
Time Frame
Baseline up to Week 12
Title
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Reported as TEAEs
Description
Twelve-lead ECGs were performed at a consistent time of day throughout the study. Electrocardiograms were performed only after the participant 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. Number of participants with potentially clinically significant abnormalities in ECG reported as TEAEs presented here. The Investigator determined whether abnormal assessment results were potentially clinically significant or not.
Time Frame
Baseline up to Week 12
Title
Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Echocardiograms (ECHO)
Description
Standard, 2-dimensional ECHOs were performed at a consistent time of day throughout the study. Cardiac function events included cardiomegaly, tachycardia, and dyspnoea. The ECHO was reviewed and interpreted by medically qualified personnel. Number of participants with potentially clinically significant abnormalities in ECHO were reported.
Time Frame
Baseline up to Week 12
Title
Part 2a: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 144 in Total Golodirsen Group
Description
6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course of 25 meters for 6 minutes (timed), and the distance walked (in meters) was recorded. Change from baseline in 6MWT distance at Week 144 in total golodirsen group was reported.
Time Frame
Baseline and Week 144
Title
Part 2b: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 144 in Untreated Group (Non-exon 53 Amenable Participants)
Description
6MWT was performed by standardized procedures for all participants. Participants were asked to walk a set course of 25 meters for 6 minutes (timed), and the distance walked (in meters) was recorded. Change from baseline in 6MWT distance at Week 144 in untreated group (non-exon 53 amenable participants) was calculated.
Time Frame
Baseline and Week 144
Title
Part 2a: Change From Baseline in Dystrophin Protein Levels Determined by Western Blot at Week 48 in Total Golodirsen Group
Description
Change from baseline in dystrophin protein levels (in muscle biopsy samples) was determined by Western blot in total golodirsen group.
Time Frame
Baseline, Week 48
Secondary Outcome Measure Information:
Title
Part 1: Maximum Plasma Concentration (Cmax) of Golodirsen
Description
Maximum Concentration (Cmax) of golodirsen in plasma was evaluated.
Time Frame
Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)
Title
Part 1: Time to Reach Maximum Plasma Concentration (Tmax) of Golodirsen
Description
Time to reach maximum plasma concentration (Tmax) of golodirsen was evaluated.
Time Frame
Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)
Title
Part 1: Area Under the Concentration-Time Curve From Time Zero Extrapolated to the Infinity (AUCinf) of Golodirsen in Plasma
Description
Area under the concentration-time curve from time zero extrapolated to the infinity was evaluated.
Time Frame
Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)
Title
Part 1: Apparent Volume of Distribution at Steady State (Vss) of Golodirsen
Description
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution at steady state of golodirsen was evaluated.
Time Frame
Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)
Title
Part 1: Elimination Half-life (T1/2) of Golodirsen
Description
T1/2 is the time measured for the plasma concentration of drug to decrease by one half. T1/2 of golodirsen was evaluated.
Time Frame
Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)
Title
Part 1: Total Clearance (CL) of Golodirsen
Description
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame
Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)
Title
Part 1: Mean Residence Time (MRT) of Golodirsen
Description
MRT= AUMCinf/AUCinf, where AUMCinf is the area under the first moment curve from time 0 extrapolated to infinite time, calculated using the linear/log trapezoidal method. Mean residence time of golodirsen was evaluated.
Time Frame
Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)
Title
Part 1: Renal Clearance (CLR) of Golodirsen
Description
Renal clearance was calculated using the partial AUC0-24 from the non-compartmental analysis in plasma and AE0-24. AUC0-24 was defined as area under the plasma concentration-time curve, from time 0 to 24 hours after completion of dosing. AE0-24 was defined as total cumulative amount excreted from 0 to 24 hours. Summarized data of all urine collection intervals are reported.
Time Frame
0 to 1440 min after initiation of dosing on Day 1
Title
Part 2a: Percent Change From Baseline in Forced Vital Capacity Predicted (FVC%p) at Week144 in Total Golodirsen Group
Description
FVC was the total amount of air exhaled during the forced expiratory volume test that was measured during spirometry and the most important measurement of lung function. This test required participant to breath into a tube connected to a machine that measures the amount of air that can be moved in and out of the lungs after taking an inhaled bronchodilator medicine which was used to dilate participant bronchial (breathing) tubes. Percent of predicted FVC = (observed value)/ (predicted value) * 100%.
Time Frame
Baseline, Week 144
Title
Part 2b: Percent Change From Baseline in Forced Vital Capacity Predicted (FVC%p) at Week144 in Untreated Group (Non-exon 53 Amenable Participants)
Description
FVC was the total amount of air exhaled during the forced expiratory volume test that was measured during spirometry and is the most important measurement of lung function. This test requires participant to breath into a tube connected to a machine that measures the amount of air that can be moved in and out of the lungs after taking an inhaled bronchodilator medicine which was used to dilate participant bronchial (breathing) tubes. Percent of predicted FVC = (observed value)/ (predicted value) * 100%.
Time Frame
Baseline, Week 144
Title
Part 2a: Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 in Total Golodirsen Group
Description
Change from baseline in dystrophin Intensity levels (in muscle biopsy samples) was determined by Immunohistochemistry in total golodirsen group.
Time Frame
Baseline, Week 48
Title
Part 2a: Percent Change From Baseline in Exon 53 Skipping Determined by Reverse Transcription Polymerase Chain Reaction (PCR) at Week 48 in Total Golodirsen Group
Description
Percent change from baseline in Exon 53 skipping (in muscle biopsy samples) was determined by reverse transcription polymerase chain reaction in total golodirsen group.
Time Frame
Baseline, Week 48
Title
Part 2a: Percent Change From Baseline in Dystrophin Positive Fibers Determined by Immunohistochemistry (IHC) at Week 48 in Total Golodirsen Group
Description
Percent change from baseline in dystrophin positive fibers (in muscle biopsy samples) were determined by Immunohistochemistry at Week 48 in total golodirsen group.
Time Frame
Baseline, Week 48
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosed with DMD, genotypically confirmed.
Intact right and left biceps muscles or an alternative upper arm muscle group.
Stable pulmonary and cardiac function.
Minimum performance on 6MWT, North Star Ambulatory Assessment, and rise (Gowers) test as specified in the study protocol.
On a stable dose of corticosteroids for at least 6 months.
Exclusion Criteria:
Previous treatment with the experimental agents BMN-195 (SMT C1100) or PRO053.
Current or previous treatment with any other experimental treatments within 12 weeks prior to study entry.
Major surgery within the last 3 months.
Presence of other clinically significant illness.
Major change in physical therapy regime within the last 3 months.
Other inclusion and exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sarepta Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02116
Country
United States
Facility Name
Institute de Myologie
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Policlinico Universitario A Gemelli
City
Rome
ZIP/Postal Code
00168
Country
Italy
Facility Name
Great Ormond Street Hospital for Children NHS Foundation Trust
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Name
Newcastle University Hospital
City
Newcastle
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
32139505
Citation
Frank DE, Schnell FJ, Akana C, El-Husayni SH, Desjardins CA, Morgan J, Charleston JS, Sardone V, Domingos J, Dickson G, Straub V, Guglieri M, Mercuri E, Servais L, Muntoni F; SKIP-NMD Study Group. Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology. 2020 May 26;94(21):e2270-e2282. doi: 10.1212/WNL.0000000000009233. Epub 2020 Mar 5. Erratum In: Neurology. 2023 May 9;100(19):936.
Results Reference
background
PubMed Identifier
34788571
Citation
Servais L, Mercuri E, Straub V, Guglieri M, Seferian AM, Scoto M, Leone D, Koenig E, Khan N, Dugar A, Wang X, Han B, Wang D, Muntoni F; SKIP-NMD Study Group. Long-Term Safety and Efficacy Data of Golodirsen in Ambulatory Patients with Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A First-in-human, Multicenter, Two-Part, Open-Label, Phase 1/2 Trial. Nucleic Acid Ther. 2022 Feb;32(1):29-39. doi: 10.1089/nat.2021.0043. Epub 2021 Nov 17.
Results Reference
derived
Learn more about this trial
Phase I/II Study of SRP-4053 in DMD Patients
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