Clinical trial NCT03375255: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Dose of SRP-5051 (Vesleteplirsen) in Patients With Duchenne Muscular Dystrophy (DMD)
Official title: A Phase 1 Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of a Single Dose of SRP-5051 in Patients With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Muscular Dystrophy, Duchenne
Keywords: Duchenne Muscular Dystrophy
Exon Skipping
DMD
Exon 51
Ambulatory
Pediatric
Nonambulatory
Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO)
Duchenne
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-12-18
Enrollment: 15
Sex: MALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of 5 escalating doses of SRP-5051 (vesleteplirsen) administered as a single dose to patients with DMD amenable to exon 51 skipping treatment.


Eligibility criteria: Inclusion Criteria:

* Has a genetic diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51 skipping treatment
* Has been on a stable dose of oral corticosteroids for at least 12 weeks prior to study drug administration with continued dosing of oral corticosteroids while participating in the study\*, or has not received corticosteroids for at least 12 weeks prior to study drug administration and will not initiate dosing of oral corticosteroids while participating in the study

Exclusion Criteria:

* Has a left ventricular ejection fraction (LVEF) less than (\<) 40 percent (%) based on an echocardiogram (ECHO) performed within 3 months prior to Screening or at the Screening visit
* Has a QT interval corrected with Fridericia's method (QTcF) \>= 450 millisecond (msec) on the Screening electrocardiogram (ECG)
* Initiation or change of dosing (except for modifications to accommodate changes in weight) within 12 weeks prior to Screening and while participating in the study for any of the following: angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blocking agents (ARBs), beta-blockers, or potassium
* Requires antiarrhythmic and/or diuretic therapy for heart failure
* Forced vital capacity (FVC) \<40% of predicted value within 3 months of Screening or at the Screening visit
* Known kidney disease or had an acute kidney injury within 6 months prior to Screening
* Treatment with eteplirsen or drisapersen within 6 months prior to Screening, or any experimental gene therapy for the treatment of DMD at any time
* Use of any herbal medication/supplement containing aristolochic acid

Other inclusion/exclusion criteria apply.

\*The dose of steroids must remain constant except for modifications to accommodate changes in weight.

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs)
timeFrame: From signing of informed consent to 12 weeks after the last infusion of SRP-5051 (Up to 14 weeks)
Secondary outcomes:
measure: Maximum Plasma concentration (Cmax) of SRP-5051
timeFrame: Pre-dose, mid-infusion, end of infusion, post-dose (0.25, 0.5, 1, 2, 4, 8, 12 hours)
measure: Area under the plasma concentration versus time curve (AUC) of SRP-5051
timeFrame: Pre-dose, mid-infusion, end of infusion, post-dose (0.25, 0.5, 1, 2, 4, 8, 12 hours)
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Neuromuscular Research Center
state: California
city: Gulf Breeze
country: United States
facility: NW FL Clinical Research Group, LLC
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research, LLC
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: