Phase 1/2 Study in Boys With Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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The MoveDMD study is a 3-part, Phase 1/2, multi-site study to evaluate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of edasalonexent (also known as CAT-1004) in pediatric patients with a genetically confirmed diagnosis of DMD. Male patients from ≥4 to <8 years of age will be enrolled. Edasalonexent is an orally administered small molecule targeted to inhibit activated NF-κB, a molecule that is activated from infancy in DMD and which is central to causing muscle damage and preventing muscle regeneration. Data on magnetic resonance imaging of the lower and upper leg muscles, physical function (including timed function tests) and muscle strength will be studied.

Detailed Description
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Part A was a 1-week, open-label study to assess safety, tolerability, pharmacokinetics and biomarkers for three dose levels of edasalonexent and is now complete. Part B was a randomized, double-blind, placebo-controlled, multiple dose study to evaluate the safety, efficacy, PK, and PD of edasalonexent over 12 weeks. Patients who participated in Part A also participated in Part B, along with newly enrolled patients. Patients received either edasalonexent 67 mg/kg/day, edasalonexent 100 mg/kg/day, or placebo in Part B. Part B is now complete. Following completion of Part B, patients receive edasalonexent for 138 weeks in Part C, the open-label portion of the MoveDMD study. Patients on the 67 mg/kg/day treatment moved to the 100 mg/kg/day treatment. Patients on the 100 mg/kg/day treatment remained on the 100 mg/kg/day treatment. If clinically indicated, concomitant treatment with eteplirsen (Exondys 51™) may be acceptable in patients with amenable gene mutations during Part C after the patient has been exposed to edasalonexent for 6 months. **Following completion of MoveDMD Part C, access to edasalonexent for trial participants will continue through the open-label extension study, GalaxyDMD.**

Official Title
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A Phase 1/2 Study of Edasalonexent (CAT-1004) in Pediatric Patients With Duchenne Muscular Dystrophy

Conditions
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Muscular Dystrophy, Duchenne

Intervention / Treatment
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* Drug: Edasalonexent
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent from parent or legal guardian prior to participation and, for patients who are 7 years of age, written assent from patient Diagnosis of DMD based on a clinical phenotype with increased serum CK and the presence of a mutation in the dystrophin gene known to be associated with a DMD phenotype Ability to walk independently (assistive devices are permitted) Adequate immunization for influenza and varicella Exclusion Criteria: Use of corticosteroids within prior 6 months of treatment initiation or planning to initiate steroid therapy within the next 6 months Other prior or ongoing significant medical conditions Exposure to another investigational drug (such as eteplirsen or idebenone) within 28 days prior to start of study treatment or ongoing participation in any other therapeutic clinical trial Note: There are separate criteria for patients who participated in Part A versus newly enrolling patients. New patients must meet all of the Part A entry criteria to participate in Part B. Patients who participated in Part A must meet the following criteria to participate in Part B: Completed Part A Continue to meet all of the Part A entry criteria, including an absence of safety concerns (however, patients may be ≥8 years of age) There are no entry criteria for Part C; all patients who complete Part B will automatically continue in Part C

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 7 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1<br>Edasalonexent 67 mg/kg/day. Capsules taken by mouth two times per day | Drug: Edasalonexent<br> <br> * Other names: Edasa;|
| Experimental: Dose 2<br>Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day | Drug: Edasalonexent<br> <br> * Other names: Edasa;|
| Placebo Comparator: Placebo<br>Matching placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in the Lower Leg Composite of the MRI T2 Relaxation Time (LLC5-T2) - Part B | The LLC5-T2 calculated from the unweighted average of the T2 relaxation times of all 5 lower leg muscles for each patient at each evaluation (the medial gastrocnemius, peroneals, soleus, tibialis anterior, and tibialis posterior muscles). Increases in LLC5-T2 relaxation time indicate muscle damage, inflammation, edema, and fat infiltration and are highly correlated with muscle fat | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Speed of Completing the 10-meter Walk/Run Test (10MWT) at Week 12 - Part B and Part C | The 10MWT determines the speed to walk a distance of 10 meters. The initial measurement was made in seconds and the speed of completing the test (i.e., calculated as the reciprocals of the time to complete; speed=1/time) is provided as the measure. For patients who are not able to complete the test, the speed of 0 will be imputed. | Baseline to Week 12 | 
| Change From Baseline in the Speed of Completing the 4-Stairs Climb Task at Week 12 - Part B and Part C | The 4-stair climb test determines the speed to climb 4 standard steps. The initial measurement was made in seconds and the speed of completing the test (i.e., calculated as the reciprocals of the time to complete; speed=1/time) is provided as the measure. For patients who are not able to complete the test, the speed of 0 will be imputed. | Baseline to Week 12 | 
| Change From Baseline in the Speed of Completing the Stand From Supine Task at Week 12 - Part B and Part C | The stand from supine test determines the speed to stand from a supine position. The initial measurement was made in seconds and the speed of completing the test (i.e., calculated as the reciprocals of the time to complete; speed=1/time) is provided as the measure. For patients who are not able to complete the test, the speed of 0 will be imputed. | Baseline to Week 12 | 
| Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs). | A TEAE was any adverse event (AE) that started during or after the first dose of IP through the end of the safety follow-up period. Part B TEAEs were those that started on or after the first dose date in Part B through the date of Week 12 clinic dose. TEAEs for the Part C (Active B or C) analysis were those that started on or after the first dose date of active treatment in Part B or Part C. Drug related AEs included those marked as Related or Possibly Related to the study treatment. | Screening to Week 152 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscular Dystrophies, Musculoskeletal Diseases, Nervous System Diseases, Neuromuscular Diseases, Duchenne muscular dystrophy, DMD, dystrophin, dystrophy, Duchenne