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

Primary Purpose

Muscular Dystrophy, Duchenne

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Edasalonexent
Placebo
Sponsored by
Catabasis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Muscular Dystrophy, Duchenne focused on measuring Muscular Dystrophies, Musculoskeletal Diseases, Neuromuscular Diseases, Duchenne muscular dystrophy, DMD, dystrophin, dystrophy, Duchenne

Eligibility Criteria

4 Years - 7 Years (Child)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Arkansas Children's Hospital
  • Children's Hospital of Los Angeles
  • UC Davis
  • Nemours Children's Hospital
  • Rare Disease Research, LLC
  • Rush University Children's Hospital
  • University of Iowa Children's Hospital
  • University of Kansas Medical Center
  • Kennedy Krieger Institute
  • Johns Hopkins School of Medicine
  • Boston Children's Hospital
  • University of Michigan
  • University of Minnesota
  • Las Vegas Clinic
  • Cincinnati Children's Hospital
  • MetroHealth Medical Center
  • Shriners Hospitals for Children
  • Children's Hospital of Philadelphia
  • Vanderbilt University Medical Center
  • Cook Children's Medical Center
  • University of Texas Health Science Center at San Antonio
  • University of Utah
  • Children's Hospital of the King's Daughters
  • Children's Hospital of Richmond at VCU
  • The Children's Hospital at Westmead
  • Children's Health Queensland Children's Hospital and Health Service
  • Royal Children's Hospital
  • Alberta Children's Hospital
  • London Health Sciences Centre - Children's Hospital
  • Children's Hospital of Eastern Ontario
  • CHU Sainte-Justine
  • University of Hamburg
  • University of Munich
  • Children's University Hospital
  • Hadassah Medical Center
  • Queen Silvia Children's Hospital
  • Bristol Children's Hospital
  • Evelina Children's Hospital
  • Great Ormond Street Hospital (GOSH)
  • Royal Manchester Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dose 1

Placebo

Arm Description

Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day.

Matching placebo

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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)
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
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
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).

Full Information

First Posted
October 8, 2018
Last Updated
June 16, 2022
Sponsor
Catabasis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03703882
Brief Title
Phase III Study of Edasalonexent in Boys With Duchenne Muscular Dystrophy
Acronym
PolarisDMD
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients With Duchenne Muscular Dystrophy
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
October 2, 2018 (Actual)
Primary Completion Date
September 22, 2020 (Actual)
Study Completion Date
September 22, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Catabasis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Dystrophy, Duchenne
Keywords
Muscular Dystrophies, Musculoskeletal Diseases, Neuromuscular Diseases, Duchenne muscular dystrophy, DMD, dystrophin, dystrophy, Duchenne

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
131 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose 1
Arm Type
Experimental
Arm Description
Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo
Intervention Type
Drug
Intervention Name(s)
Edasalonexent
Other Intervention Name(s)
Edasa, CAT-1004
Intervention Description
100 mg/kg/day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Change From Baseline in North Star Ambulatory Assessment (NSAA)
Description
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
Time Frame
Baseline (Day 1) to Week 52
Secondary Outcome Measure Information:
Title
Change From Baseline in 10-meter Walk/Run Test
Description
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)
Time Frame
Baseline (Day 1) to Week 52
Title
Change From Baseline in Time to Stand From Supine
Description
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
Time Frame
Baseline (Day 1) to Week 52
Title
Change From Baseline in 4-stair Climb
Description
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
Time Frame
Baseline (Day 1) to Week 52
Title
Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
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).
Time Frame
Up to Week 52

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
7 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joanne M Donovan, Chief Medical Officer, MD, PhD
Organizational Affiliation
Catabasis Pharmaceuticals
Official's Role
Study Chair
Facility Information:
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
UC Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Nemours Children's Hospital
City
Orlando
State/Province
Florida
ZIP/Postal Code
32827
Country
United States
Facility Name
Rare Disease Research, LLC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
Rush University Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Iowa Children's Hospital
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Kansas Medical Center
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Kennedy Krieger Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Johns Hopkins School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Las Vegas Clinic
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89145
Country
United States
Facility Name
Cincinnati Children's Hospital
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
MetroHealth Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
Shriners Hospitals for Children
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
Cook Children's Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Children's Hospital of the King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23510
Country
United States
Facility Name
Children's Hospital of Richmond at VCU
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
The Children's Hospital at Westmead
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Children's Health Queensland Children's Hospital and Health Service
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Royal Children's Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Alberta Children's Hospital
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3B 6A8
Country
Canada
Facility Name
London Health Sciences Centre - Children's Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4G5
Country
Canada
Facility Name
Children's Hospital of Eastern Ontario
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L1
Country
Canada
Facility Name
CHU Sainte-Justine
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3T 1C5
Country
Canada
Facility Name
University of Hamburg
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
University of Munich
City
Munich
ZIP/Postal Code
80337
Country
Germany
Facility Name
Children's University Hospital
City
Dublin
ZIP/Postal Code
1
Country
Ireland
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
9124001
Country
Israel
Facility Name
Queen Silvia Children's Hospital
City
Gothenburg
ZIP/Postal Code
41685
Country
Sweden
Facility Name
Bristol Children's Hospital
City
Bristol
ZIP/Postal Code
BS2 8AE
Country
United Kingdom
Facility Name
Evelina Children's Hospital
City
London
ZIP/Postal Code
SE1 7EU
Country
United Kingdom
Facility Name
Great Ormond Street Hospital (GOSH)
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Name
Royal Manchester Children's Hospital
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
34120912
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.
Results Reference
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Phase III Study of Edasalonexent in Boys With Duchenne Muscular Dystrophy

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