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

• ClinicalTrials.gov Identifier: NCT03703882
• Recruitment Status: Completed
• First Posted: October 12, 2018
• Results First Posted: June 21, 2022
• Last Update Posted: June 21, 2022
• Sponsor: Catabasis Pharmaceuticals
• Information provided by (Responsible Party): Catabasis Pharmaceuticals

Tracking Information

• First Submitted Date: October 8, 2018
• First Posted Date: October 12, 2018
• Results First Submitted Date: January 10, 2022
• Results First Posted Date: June 21, 2022
• Last Update Posted Date: June 21, 2022
• Actual Study Start Date: October 2, 2018
• Actual Primary Completion Date: September 22, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 16, 2022)

Change From Baseline in North Star Ambulatory Assessment (NSAA) [ Time Frame: Baseline (Day 1) to Week 52 ]

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

• Original Primary Outcome Measures (submitted: October 9, 2018): Change from baseline in North Star Ambulatory Assessment (NSAA) [ Time Frame: 52 Weeks ]

Current Secondary Outcome Measures (submitted: June 16, 2022)

• Change From Baseline in 10-meter Walk/Run Test [ Time Frame: Baseline (Day 1) to Week 52 ]
  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)
• Change From Baseline in Time to Stand From Supine [ Time Frame: Baseline (Day 1) to Week 52 ]
  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
• Change From Baseline in 4-stair Climb [ Time Frame: Baseline (Day 1) to Week 52 ]
  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
• Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 52 ]
  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).

Original Secondary Outcome Measures (submitted: October 9, 2018)

• Safety and tolerability measured by number of treatment- emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: 52 Weeks ]
• Change from baseline in 10-meter walk/run test [ Time Frame: 52 Weeks ]
• Change from baseline in time to stand from supine [ Time Frame: 52 Weeks ]
• Change from baseline in 4-stair climb [ Time Frame: 52 Weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: October 9, 2018)

• Change from baseline in muscle strength testing assessed by knee extension and elbow flexion [ Time Frame: 52 Weeks ]
• Change from baseline in the Performance of Upper Limb (PUL) Scale to assess upper limb function [ Time Frame: 52 Weeks ]
• Change from baseline in parent/proxy reported physical functioning/quality of life assessed by the Pediatric Outcome Data Collection Instrument (PODCI) Questionnaire [ Time Frame: 52 Weeks ]

Descriptive Information

• Brief Title: 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

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Muscular Dystrophy, Duchenne

Intervention

• Drug: Edasalonexent
  100 mg/kg/day
  Other Names:

  • Edasa
  • CAT-1004
• Drug: Placebo
  Placebo

Study Arms

• Experimental: Dose 1
  Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day.
  Intervention: Drug: Edasalonexent
• Placebo Comparator: Placebo
  Matching placebo
  Intervention: Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 10, 2019): 131
• Original Estimated Enrollment (submitted: October 9, 2018): 125
• Actual Study Completion Date: September 22, 2020
• Actual Primary Completion Date: September 22, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 4 Years to 7 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Germany, Ireland, Israel, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT03703882
• Other Study ID Numbers: CAT-1004-301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Catabasis Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Catabasis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Catabasis Pharmaceuticals
• Verification Date: June 2022