Phase III Study of Edasalonexent in Boys With Duchenne Muscular Dystrophy

Muscular Dystrophy, Duchenne Clinical Trial

— PolarisDMD  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients With Duchenne Muscular Dystrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03703882
• Other study ID #: CAT-1004-301
• Status: Completed
• Phase: Phase 3
• Start date: October 2, 2018
• Est. completion date: September 22, 2020

Study information

• Verified date: June 2022
• Source: Catabasis Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 131
• Est. completion date: September 22, 2020
• Est. primary completion date: September 22, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 7 Years

Eligibility

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

Related Conditions & MeSH terms

• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Edasalonexent
100 mg/kg/day
• Placebo
Placebo

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Children's Health Queensland Children's Hospital and Health Service	South Brisbane	Queensland
Australia	The Children's Hospital at Westmead	Westmead	New South Wales
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	London Health Sciences Centre - Children's Hospital	London	Ontario
Canada	CHU Sainte-Justine	Montréal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Germany	University of Hamburg	Hamburg
Germany	University of Munich	Munich
Ireland	Children's University Hospital	Dublin
Israel	Hadassah Medical Center	Jerusalem
Sweden	Queen Silvia Children's Hospital	Gothenburg
United Kingdom	Bristol Children's Hospital	Bristol
United Kingdom	Evelina Children's Hospital	London
United Kingdom	Great Ormond Street Hospital (GOSH)	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United States	University of Michigan	Ann Arbor	Michigan
United States	Rare Disease Research, LLC	Atlanta	Georgia
United States	Johns Hopkins School of Medicine	Baltimore	Maryland
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Rush University Children's Hospital	Chicago	Illinois
United States	Cincinnati Children's Hospital	Cincinnati	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	University of Kansas Medical Center	Fairway	Kansas
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Iowa Children's Hospital	Iowa City	Iowa
United States	Las Vegas Clinic	Las Vegas	Nevada
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Nemours Children's Hospital	Orlando	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Shriners Hospitals for Children	Portland	Oregon
United States	Children's Hospital of Richmond at VCU	Richmond	Virginia
United States	UC Davis	Sacramento	California
United States	University of Utah	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Catabasis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Ireland,  Israel,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in North Star Ambulatory Assessment (NSAA)	To assess change from baseline in North Star Ambulatory Assessment(NSAA) Total Score at Wk52. NSAA is clinician-reported outcome instrument designed to measure ambulatory function in males with Duchenne muscular dystrophy(DMD). Patients asked to perform 17 different functional activities,including 10MWT,rising from sit to stand,standing on one leg,climbing & descending a step,stand from supine, lifting the head, standing on heels, & jumping. Each function activity will be scored as0=(unable to achieve independently),scored as1=(modified method but achieves goal independent of physical assistance from another),or scored as2=(no obvious modification of activity)or "Not Scored". If NSAA test was performed & any of the individual items are scored as "not scored"(i.e, for reasons unrelated to patients physical capabilities), corresponding total score will be set to missing. Sum of 17 scores will be used to form an ordinal total score(range 0-34).Higher scores imply better functional status	Baseline (Day 1) to Week 52
Secondary	Change From Baseline in 10-meter Walk/Run Test	To assess the changes from baseline to Week 52 on the 10-meter walk/run test (10MWT). For timed function tests (TFTs), the time will be set to 12 seconds and the speed to 0 if the TFT assessment meets the following TFT grading criteria. Grade of 1 or 2 (from a 6-point scale). 1=Unable to walk independently 2=Unable to walk independently but can walk with knee-ankle foot orthoses or support from a person 3=Highly adapted wide based lordotic gait. Cannot increase walking speed 4=Moderately adapted gait. Can pick up speed but cannot run 5=Able to pick up speed, but runs with a double stance phase, i.e. cannot achieve both feet off the ground 6=Runs and gets both feet off the ground (with no double stance phase)	Baseline (Day 1) to Week 52
Secondary	Change From Baseline in Time to Stand From Supine	To assess the change from baseline in the stand from supine speed at Week 52. For timed function tests (TFTs) , the time will be set to 12 seconds and the speed to 0 if the TFT assessment meets the following TFT grading criteria. Grade of 1 or 2 (from a 6-point scale). 1 = Unable to stand from supine, even with use of a chair, 2 = Assisted Gowers - requires furniture for assist in arising from supine to full upright posture (no time to be recorded) 3=Rolls over, stands up with both hands "climbing up" the legs to achieve full upright posture 4=Rolls over, stands up with 1 hand support on leg 5=Rolls to the side and stands up with one or both hands on the floor to start to rise but does not touch legs 6=Stands up without rolling over or using hands on legs or floor	Baseline (Day 1) to Week 52
Secondary	Change From Baseline in 4-stair Climb	To assess the change from baseline to Week 52 on the 4-Stair Climb. For timed function tests (TFTs) , the time will be set to 12 seconds and the speed to 0 if the TFT assessment meets the following TFT grading criteria. Grade of 1(from a 6-point scale)1=Unable to climb 4 standard stairs(no time recorded) 2=Climbs 4 standard stairs "marking time"(climbs one foot at a time, with both feet on a step before moving to next step), uses both arms on one or both handrails or uses 1 handrail and the other arm pushes on the leg 3=Climbs 4 standard stairs "marking time", using one arm on one handrail or one hand pushing on leg or body 4=Climbs 4 standard stairs "marking time", not needing handrail and not using hands to push on leg 5=Climbs 4 standard stairs alternating feet, needs handrail/s for support or uses arms to push on the leg or body 6=Climbs 4 standard stairs alternating feet, not needing handrail support or using arm to push on the leg	Baseline (Day 1) to Week 52
Secondary	Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Adverse events that occurred from the time of the administration of the first dose of investigational product (IP) through the end of the safety follow-up were considered treatment-emergent AEs (TEAEs). Serious adverse event (SAE).	Up to Week 52