Phase III Study of Edasalonexent in Boys With Duchenne Muscular Dystrophy (PolarisDMD)

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

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.

Study Overview

• Status: Completed
• Conditions: Muscular Dystrophy, Duchenne
• Intervention / Treatment: Drug: Placebo; Drug: Edasalonexent

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.

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • The Children's Hospital at Westmead
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Children's Health Queensland Children's Hospital and Health Service
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
  • Ontario
    • London, Ontario, Canada, N6A 4G5
      • London Health Sciences Centre - Children's Hospital
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
  • Quebec
    • Montréal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine
• Germany
  • Hamburg, Germany, 20246
    • University of Hamburg
  • Munich, Germany, 80337
    • University of Munich
• Ireland
  • Dublin, Ireland, 1
    • Children's University Hospital
• Israel
  • Jerusalem, Israel, 9124001
    • Hadassah Medical Center
• Sweden
  • Gothenburg, Sweden, 41685
    • Queen Silvia Children's Hospital
• United Kingdom
  • Bristol, United Kingdom, BS2 8AE
    • Bristol Children's Hospital
  • London, United Kingdom, SE1 7EU
    • Evelina Children's Hospital
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital (GOSH)
  • Manchester, United Kingdom, M13 9WL
    • Royal Manchester Children's Hospital
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Of Los Angeles
    • Sacramento, California, United States, 95817
      • UC Davis
  • Florida
    • Orlando, Florida, United States, 32827
      • Nemours Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Rare Disease Research, LLC
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Children's Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Children's Hospital
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Kennedy Krieger Institute
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Nevada
    • Las Vegas, Nevada, United States, 89145
      • Las Vegas Clinic
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Shriners Hospitals for Children
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Children's Hospital of the King's Daughters
    • Richmond, Virginia, United States, 23298
      • Children's Hospital of Richmond at VCU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 7 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo	Drug: Placebo; Placebo
Experimental: Dose 1; Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day.	Drug: Edasalonexent; 100 mg/kg/day; Other Names: Edasa; CAT-1004

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Catabasis Pharmaceuticals
• Investigators: Study Chair: Joanne M Donovan, Chief Medical Officer, MD, PhD, Catabasis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2018
• Primary Completion (Actual): September 22, 2020
• Study Completion (Actual): September 22, 2020

Study Registration Dates

• First Submitted: October 8, 2018
• First Submitted That Met QC Criteria: October 9, 2018
• First Posted (Actual): October 12, 2018

Study Record Updates

• Last Update Posted (Actual): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 16, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Musculoskeletal Diseases; Neuromuscular Diseases; DMD; Duchenne; Muscular Dystrophies; Duchenne muscular dystrophy; dystrophin; dystrophy
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: CAT-1004-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No