Clinical trial NCT03703882: Phase III Study of Edasalonexent in Boys With Duchenne Muscular Dystrophy
Official title: A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients With Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Muscular Dystrophy, Duchenne
Keywords: Muscular Dystrophies
Musculoskeletal Diseases
Neuromuscular Diseases
Duchenne muscular dystrophy
DMD
dystrophin
dystrophy
Duchenne
Lead sponsor: Catabasis Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-10-12
Enrollment: 131
Sex: MALE
Minimum age (years): 4
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The PolarisDMD study is a Phase 3, global study to evaluate the efficacy and safety of edasalonexent in pediatric patients with a genetically confirmed diagnosis of DMD. Male patients from 4-7 years of age (up to 8th birthday) will be enrolled.

Edasalonexent is an orally administered small molecule that inhibits NF-kB, which is the key link between loss of dystrophin and disease pathology and plays a fundamental role in the initiation and progression of skeletal and cardiac muscle disease in DMD.

Detailed description: The study includes a 52-week, randomized, double-blind, placebo-controlled period, followed by a 2-week follow- up. Approximately 125 boys with DMD will be enrolled in this trial, with 2 boys receiving edasalonexent for every 1 boy receiving placebo.

Following completion of the treatment period, patients may elect to continue in a separate open-label extension study.

Eligibility criteria: Inclusion Criteria:

* Written consent/assent by patient and/or legal guardian as per regional and/or Institutional Review Board (IRB)/Independent Ethics Committee (IEC) requirements
* Diagnosis of DMD based on a clinical phenotype with increased serum creatine kinase (CK) and documentation of mutation(s) in the dystrophin gene known to be associated with a DMD phenotype
* Able to perform stand from supine without assistance in ≤ 10 seconds
* Able to perform the 10MWT and 4-stair climb
* Followed by a doctor or medical professional who coordinates Duchenne care on a regular basis and willingness to disclose patient's study participation with medical professionals

Exclusion Criteria:

* Use of corticosteroids within 24 weeks prior to Day 1; use of inhaled, intranasal, and topical corticosteroids is permitted
* Use of another investigational drug, idebenone, or dystrophin-focused therapy within 4 weeks. Exception: Patients who have received at least 24 weeks of a stable dose of eteplirsen prior to Day 1, and expected to continue treatment, will be eligible
* Use of the following within 4 weeks prior to Day 1: immunosuppressive therapy, warfarin, phenytoin, S mephenytoin, cyclosporine, dihydroergotamine, ergotamine, fentanyl, alfentanil, pimozide, quinidine, sirolimus, tacrolimus, or paclitaxel
* Use of human growth hormone within 3 months prior to Day 1
* Other prior or ongoing significant medical conditions

Primary outcomes:
measure: Change From Baseline in North Star Ambulatory Assessment (NSAA)
timeFrame: Baseline (Day 1) to Week 52
Secondary outcomes:
measure: Change From Baseline in 10-meter Walk/Run Test
timeFrame: Baseline (Day 1) to Week 52
measure: Change From Baseline in Time to Stand From Supine
timeFrame: Baseline (Day 1) to Week 52
measure: Change From Baseline in 4-stair Climb
timeFrame: Baseline (Day 1) to Week 52
measure: Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to Week 52
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Sacramento
country: United States
facility: UC Davis
state: California
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research, LLC
state: Georgia
city: Chicago
country: United States
facility: Rush University Children's Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Children's Hospital
state: Iowa
city: Fairway
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins School of Medicine
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Las Vegas
country: United States
facility: Las Vegas Clinic
state: Nevada
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Portland
country: United States
facility: Shriners Hospitals for Children
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Richmond
country: United States
facility: Children's Hospital of Richmond at VCU
state: Virginia
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: South Brisbane
country: Australia
facility: Children's Health Queensland Children's Hospital and Health Service
state: Queensland
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: London
country: Canada
facility: London Health Sciences Centre - Children's Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Montréal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Hamburg
country: Germany
facility: University of Hamburg
city: Munich
country: Germany
facility: University of Munich
city: Dublin
country: Ireland
facility: Children's University Hospital
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Gothenburg
country: Sweden
facility: Queen Silvia Children's Hospital
city: Bristol
country: United Kingdom
facility: Bristol Children's Hospital
city: London
country: United Kingdom
facility: Evelina Children's Hospital
city: London
country: United Kingdom
facility: Great Ormond Street Hospital (GOSH)
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
Study officials:
affiliation: Catabasis Pharmaceuticals
name: Joanne M Donovan, Chief Medical Officer, MD, PhD
role: STUDY_CHAIR
References:
citation: Finkel RS, McDonald CM, Lee Sweeney H, Finanger E, Neil Knierbein E, Wagner KR, Mathews KD, Marks W, Statland J, Nance J, McMillan HJ, McCullagh G, Tian C, Ryan MM, O'Rourke D, Muller-Felber W, Tulinius M, Burnette WB, Nguyen CT, Vijayakumar K, Johannsen J, Phan HC, Eagle M, MacDougall J, Mancini M, Donovan JM; (For the PolarisDMD Study Group). A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial. J Neuromuscul Dis. 2021;8(5):769-784. doi: 10.3233/JND-210689.