Clinical trial NCT02255552: Study of Eteplirsen in DMD Patients
Official title: An Open-Label, Multi-Center, Study With a Concurrent Untreated Control Arm to Evaluate the Efficacy and Safety of Eteplirsen in Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Duchenne Muscular Dystrophy (DMD)
Keywords: DMD, Duchenne, Eteplirsen, dystrophy, dystrophin, exon 51
Lead sponsor: Sarepta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2014-10-02
Enrollment: 109
Sex: MALE
Minimum age (years): 7
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main objective of this study is to provide evidence of efficacy of eteplirsen (AVI-4658) in Duchenne muscular dystrophy (DMD) patients that are amenable to skipping exon 51. Additional objectives include evaluation of safety, biomarkers and the long-term effects of eteplirsen up to 96 weeks, followed by a safety extension (not to exceed 48 weeks).

Detailed description: This is an open-label, multi-center study to evaluate the efficacy and safety of eteplirsen in patients with genotypically confirmed Duchenne muscular dystrophy (DMD) with genetic deletions amenable to exon 51 skipping (treated group), with a concurrent control arm of DMD patients not amenable to exon 51 skipping (untreated group). Following primary efficacy endpoints, dosing will continue to week 144 to evaluate the long term effects of eteplirsen.

Patients in the treated group 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). Patients in the untreated group will not receive treatment.

Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests such as the six minute walk test. Patients in the treated group will undergo a muscle biopsy at Baseline and a second muscle biopsy over the course of the study. Patients in the untreated group will not undergo muscle biopsy.

Safety, including adverse event monitoring and routine laboratory assessments, will be continuously monitored for all patients.

Eligibility criteria: Inclusion Criteria:

* Male 7-16 years old
* Diagnosed with DMD, genotypically confirmed
* Stable dose of corticosteroids for at least 24 weeks
* Have intact right and left alternative upper muscle groups
* Mean 6MWT greater than 300m (primary analysis on 300 to 450 meters)
* Stable pulmonary and cardiac function: predicted FVC equal to or greater than 50% and LVEF of greater than 50%

Exclusion Criteria:

* Previous treatment with drisapersen or any other RNA antisense agent or any gene therapy within the last 6 months
* Participation in any other DMD interventional clinical study within 12 weeks
* Major surgery within 3 months
* Presence of other clinically significant illness
* Major change in the physical therapy regime within 3 months

Other inclusion/exclusion criteria apply.

Primary outcomes:
measure: Change From Baseline in the 6 Minute Walk Test (6MWT) Distance at Week 96
timeFrame: Baseline, Week 96
Secondary outcomes:
measure: Change From Baseline in Dystrophin Protein Levels Determined by Western Blot at Week 96
timeFrame: Baseline, Week 96
measure: Number of Participants Having Ability to Rise Independently From the Floor Determined Based on North Star Ambulatory Assessment (NSAA) at Week 96
timeFrame: Week 96
measure: Number of Participants Who Lost Ambulation (LOA) by Week 96
timeFrame: Up to Week 96
measure: Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Weeks 96
timeFrame: Baseline, Week 96
measure: Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Scores at Week 96
timeFrame: Baseline, Week 96
measure: Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 96
timeFrame: Baseline, Week 96
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Neuromuscular Research Center
state: Arizona
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital, U.C. San Diego
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine/Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Washington
country: United States
facility: Children's National Health System
state: District of Columbia
city: Gainesville
country: United States
facility: The University of Florida, Powell Gene Therapy Center
state: Florida
city: Gulf Breeze
country: United States
facility: NW FL Clinical Research Group, LLC
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research Center
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Children's Hospital
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Clinical Research Center
state: New York
city: Charlotte
country: United States
facility: Levine Childrens Hospital, Carolinas Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center (CCHMC)
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Shriners Hospital for Children
state: Oregon
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Sarepta Therapeutics, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Brogna C, Coratti G, Pane M, Ricotti V, Messina S, D'Amico A, Bruno C, Vita G, Berardinelli A, Mazzone E, Magri F, Ricci F, Mongini T, Battini R, Bello L, Pegoraro E, Baranello G, Previtali SC, Politano L, Comi GP, Sansone VA, Donati A, Bertini E, Muntoni F, Goemans N, Mercuri E; on behalf on the International DMD group. Long-term natural history data in Duchenne muscular dystrophy ambulant patients with mutations amenable to skip exons 44, 45, 51 and 53. PLoS One. 2019 Jun 25;14(6):e0218683. doi: 10.1371/journal.pone.0218683. eCollection 2019.