Phase 1/2 Study in Boys With Duchenne Muscular Dystrophy

Phase 1

Completed

• Conditions: Muscular Dystrophy, Duchenne
• Interventions: Drug: Placebo; Drug: Edasalonexent

• Registration Number: NCT02439216
• Lead Sponsor: Catabasis Pharmaceuticals

Brief Summary

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

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.\*\*

Study Timeline

• Study First Submitted: 2015-04-29
• Study First Submitted QC: 2015-05-06
• Study First Posted: 2015-05-08
• Study Start: 2016-04
• Primary Completion: 2017-01-12
• Disposition First Submitted: 2018-01-17
• Disposition First Submitted QC: 2018-01-30
• Disposition First Posted: 2018-01-31
• Study Completion: 2019-08
• Results First Submitted: 2022-01-10
• Status Verified: 2022-09
• Results First Submitted QC: 2022-09-20
• Last Update Submitted: 2022-09-20
• Results First Posted: 2022-09-23
• Last Update Posted: 2022-09-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 31

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matching placebo
Dose 1	Edasalonexent	Edasalonexent 67 mg/kg/day. Capsules taken by mouth two times per day
Dose 2	Edasalonexent	Edasalonexent 100 mg/kg/day. Capsules taken by mouth three times per day

Primary Outcome Measures

Name	Time	Method
Change From Baseline to Week 12 in the Lower Leg Composite of the MRI T2 Relaxation Time (LLC5-T2) - Part B	Baseline to Week 12	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

Secondary Outcome Measures

Name	Time	Method
Safety and Tolerability Measured by Number of Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).	Screening to Week 152	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.
Change From Baseline in the Speed of Completing the 4-Stairs Climb Task at Week 12 - Part B and Part C	Baseline to Week 12	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.
Change From Baseline in the Speed of Completing the Stand From Supine Task at Week 12 - Part B and Part C	Baseline to Week 12	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.
Change From Baseline in the Speed of Completing the 10-meter Walk/Run Test (10MWT) at Week 12 - Part B and Part C	Baseline to Week 12	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.