Muscular Dystrophy, Duchenne
Conditions
Keywords
Duchenne muscular dystrophy, Exon Skipping, DMD, Exon 51, Ambulatory, Pediatric, Nonambulatory, Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO), Duchenne
Brief summary
The purpose of this extension study is to evaluate the safety, tolerability, and pharmacokinetics of repeat administrations of SRP-5051 (vesleteplirsen) in participants with Duchenne muscular dystrophy (DMD) who participated in studies of SRP-5051.
Interventions
DRUGSRP-5051
SRP-5051 administered as an IV infusion.
Sponsors
Sarepta Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
4 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Has completed a study of SRP-5051 and continues to meet the Eligibility Criteria of Study 5051-102.
Exclusion criteria
* Initiation or change of dosing (except for modifications to accommodate changes in weight or changes in standard of care) since completing a study administering SRP-5051 and while participating in this study for any of the following: angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blocking agents (ARBs), beta-blockers, potassium and steroids\*. * Requires antiarrhythmic and/or diuretic therapy for heart failure. * Use of any herbal medication/supplement containing aristolochic acid. * Treatment with any experimental therapy since entering original study or any experimental gene therapy for the treatment of DMD at any time. * Participation in an interventional clinical trial since completing original study. Other inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | Up to approximately 135 weeks | A TEAE was any untoward medical occurrence in a clinical study participant that did not necessarily have a causal relationship with the study drug. A TEAE could, therefore, be any unfavorable and unintended symptom, sign, disease, condition, or test abnormality that occurred during or after administration of the study drug, whether or not considered related to the study drug. A summary of serious and all other non-serious TEAEs regardless of causality is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Concentration of SRP-5051 | Day 1, Day 84, every 84 days after Day 84 (up to a maximum of approximately 135 weeks) (pre-dose, immediately prior to end of infusion, up to 4-6 hours post-dose) | For pharmacokinetic (PK) analysis, plasma samples were collected pre-dose (approximately 30 minutes prior to the start of infusion), immediately prior to the end of infusion (prior to flush), and approximately 4 to 6 hours after the end of dosing. Results are reported in micrograms/liter (ug/L) and are presented as an average across the days specified in the time frame. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SRP-5051 Participants received SRP-5051 via IV infusion Q4W. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 2 |
| Overall Study | Study Terminated by Sponsor | 9 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | SRP-5051 |
|---|---|
| Age, Continuous | 16.5 years STANDARD_DEVIATION 2.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 15 |
| other Total, other adverse events | 14 / 15 |
| serious Total, serious adverse events | 6 / 15 |
Outcome results
Primary
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
A TEAE was any untoward medical occurrence in a clinical study participant that did not necessarily have a causal relationship with the study drug. A TEAE could, therefore, be any unfavorable and unintended symptom, sign, disease, condition, or test abnormality that occurred during or after administration of the study drug, whether or not considered related to the study drug. A summary of serious and all other non-serious TEAEs regardless of causality is located in the Reported Adverse Events module.
Time frame: Up to approximately 135 weeks
Population: Safety Set: all participants who started the study drug infusion.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SRP-5051 | Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | 14 Participants |
Secondary
Plasma Concentration of SRP-5051
For pharmacokinetic (PK) analysis, plasma samples were collected pre-dose (approximately 30 minutes prior to the start of infusion), immediately prior to the end of infusion (prior to flush), and approximately 4 to 6 hours after the end of dosing. Results are reported in micrograms/liter (ug/L) and are presented as an average across the days specified in the time frame.
Time frame: Day 1, Day 84, every 84 days after Day 84 (up to a maximum of approximately 135 weeks) (pre-dose, immediately prior to end of infusion, up to 4-6 hours post-dose)
Population: Pharmacokinetic Set: all participants who started the study drug infusion and had at least 1 PK concentration data collection.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SRP-5051 | Plasma Concentration of SRP-5051 | Pre-dose | 486.25 ug/L | Standard Deviation 7717.595 |
| SRP-5051 | Plasma Concentration of SRP-5051 | End of Infusion | 45244.93 ug/L | Standard Deviation 42639.411 |
| SRP-5051 | Plasma Concentration of SRP-5051 | 4-6 Hours Post-dose | 2790.32 ug/L | Standard Deviation 10941.464 |