Clinical trial NCT04004065: Two-Part Study for Dose Determination of Vesleteplirsen (SRP-5051) (Part A), Then Dose Expansion (Part B) in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment
Official title: A Phase 2, Two-Part, Multiple-Ascending-Dose Study of SRP-5051 for Dose Determination, Then Dose Expansion, in Patients With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Keywords: DMD
Duchenne
Dystrophy
Dystrophin
Exon Skipping
Ambulatory
Duchenne Muscular Dystrophy
Exon 51
Nonambulatory
Pediatric
Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO)
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-01
Enrollment: 62
Sex: MALE
Minimum age (years): 7
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will be comprised of 2 parts: 1) Part A (Multiple Ascending Dose \[MAD\]) will be conducted to evaluate the safety and tolerability of vesleteplirsen at MAD levels to determine the maximum tolerated dose (MTD), and 2) Part B will be conducted to further evaluate the vesleteplirsen doses selected in Part A. Participants enrolling in Part B will be those who completed Part A or Study 5051-102 (NCT03675126) and meet applicable eligibility criteria for Part B, as well as additional participants who meet applicable eligibility criteria for enrollment at the beginning of Part B.


Eligibility criteria: Inclusion Criteria for participants previously treated with Vesleteplirsen:

- Has received prior Vesleteplirsen treatment in Part A of this study or in Study 5051-102.

Exclusion Criteria for participants previously treated with Vesleteplirsen and new participants enrolling into Part B:

- Presence of other clinically significant illness, including cardiac, pulmonary, hepatic, renal, hematologic, immunologic, or behavioral disease, or infection or malignancy or any other condition that, in the Investigator's opinion, could interfere with participation in the trial.

Inclusion Criteria for treatment-naïve participants enrolling into Part B:

* Has a genetic diagnosis of Duchenne muscular dystrophy (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 and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight), or has not received corticosteroids for at least 12 weeks prior to study drug administration.
* Has stable pulmonary function (forced vital capacity \[FVC\] ≥40% of predicted and no requirement for nocturnal ventilation).

Exclusion Criteria for treatment-naive participants enrolling into Part B:

* History of hypomagnesemia within 12 weeks prior to Screening.
* Initiation or change of dosing (except for modifications to accommodate changes in weight or changes in standard of care) within 12 weeks prior to Screening for any of the following: angiotensin-converting enzyme inhibitors, angiotensin receptor-blocking agents, β-blockers, or potassium.
* Initiation or change of dosing within 12 weeks prior to Screening for over-the-counter preparations, such as herbal/nonherbal supplements, vitamins, minerals, and homeopathic preparations.
* Has a left ventricular ejection fraction (LVEF) \<40.0% based on an echocardiogram (ECHO) performed within 12 weeks prior to Screening or at the Screening Visit.
* Treatment with any exon 51-skipping therapy within 4 weeks prior to Screening, or with any experimental gene therapy for the treatment of DMD at any time.

Other inclusion/exclusion criteria apply.

Primary outcomes:
measure: Part A: Incidence of Adverse Events (AEs)
timeFrame: Part A: Baseline up to 75 weeks
measure: Part B: Change From Baseline in Dystrophin Protein Level at Week 28
timeFrame: Part B: Baseline, Week 28
Secondary outcomes:
measure: Part A: Pharmacokinetics (PK): Plasma Concentration of Vesleteplirsen
timeFrame: Pre-dose and at multiple time points (up to 32 hours) after end of infusion
measure: Part A: PK: Urine Concentration of Vesleteplirsen
timeFrame: Pre-dose and at multiple time periods (up to 48 hours) after end of infusion
measure: Part B: Change From Baseline in Exon-Skipping Levels at Week 28
timeFrame: Part B: Baseline, Week 28
measure: Part B: Incidence of Adverse Events (AEs)
timeFrame: Part B: Baseline up to Week 304
measure: Part B: PK: Plasma Concentration of Vesleteplirsen
timeFrame: Part B predose and at multiple timepoints (up to 48 hours) after end of infusion
measure: Part B: PK: Urine Concentration of Vesleteplirsen
timeFrame: Part B predose and at multiple timepoints (up to 48 hours) after end of infusion
measure: Part B: Change from Baseline in Percent Dystrophin-Positive Fibers (PDPF) and Mean Intensity, as Measured by Immunofluorescence Assay at Week 28
timeFrame: Part B: Baseline, Week 28
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Health
state: California
city: Farmington
country: United States
facility: Connecticut Children's
state: Connecticut
city: Gulf Breeze
country: United States
facility: Northwest Florida Clinical Research Group, LLC
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research, LLC
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Inst.
state: Kansas
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Austin
country: United States
facility: Austin Neuromuscular Center
state: Texas
city: Dallas
country: United States
facility: Children's Health Ambulatory Pavilion
state: Texas
city: Seattle
country: United States
facility: Seattle Children's
state: Washington
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: London
country: Canada
facility: Children's Hospital - London Health Sciences Centre (LHSC)
state: Ontario
city: Essen
country: Germany
facility: University of Essen - Children's Hospital
city: Munich
country: Germany
facility: Klinikum der Universität München
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
city: Torino
country: Italy
facility: A.O.U. Citta della Salute e della Scienza di Torino - SS Malattie Neuromuscolari, Department of Neurosciences
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu. U.B.
city: Valencia
country: Spain
facility: Hospital Universitari I Politecnic La Fe de Valencia
city: Liverpool
country: United Kingdom
facility: Alder Hey Children's NHS Foundation Trust
state: Lancashire
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children (Glasgow)
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: Oxford University Hospial NHS Foundation Trust, John Radcliffe Hospital
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: