A Study to Assess the Efficacy and Safety of MNK-1411 in Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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This is a multicenter, double blind, placebo controlled, multiple dose study to examine the safety and efficacy of MNK-1411 in male subjects 4 to 8 years of age (inclusive) with Duchenne Muscular Dystrophy (DMD).

Detailed Description
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The main purpose of this study is to determine the effect of MNK-1411 on motor function in participants with Duchenne Muscular Dystrophy (DMD). Information is collected only from caretakers who are fluent in English, using the Pediatric Outcomes Data Collection Instrument (PODCI). The PODCI is a validated 86-question instrument completed by the parent or legal guardian of children 2 to 10 years of age to assess a variety of health outcome measures (Uzark et al, 2012). This study will only collect information for the PODCI domains of sports and physical functioning and transfer/basic mobility.

Official Title
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A Multicenter, Randomized, Parallel Group, Double Blind, Multiple Dose, Placebo Controlled Study to Assess the Efficacy and Safety of MNK-1411 in Male Participants 4 to 8 Years of Age With Duchenne Muscular Dystrophy

Conditions
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Muscular Dystrophy, Duchenne

Intervention / Treatment
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* Drug: MNK-1411
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have a documented diagnosis of Duchenne Muscular Dystrophy (DMD) confirmed by complete dystrophin deficiency (by immunofluorescence and/or immunoblot), or identifiable mutation in the DMD gene where reading frame can be predicated as out of frame, or complete dystrophin gene sequencing consistent with DMD; AND in the opinion of the Investigator, a typical clinical profile consistent with DMD. Participants taking approved treatments for DMD (by a Health Authority) that target dystrophin gene mutations (e.g., eteplirsen or ataluren) may be enrolled in the study if they have been on a stable dose for 30 days prior to the first dose of study drug, and plan to remain on that dose throughout the study. Exclusion Criteria: Participant has had previous systemic treatment with corticosteroids within 2 months prior to the Screening Visit. Exception: In subjects who were down-titrated to a physiological dose of corticosteroids (ie, 3mg/m2 of prednisone or deflazacort) a maximum of 1 month of no greater than a physiological dose followed by 1 month completely off corticosteroids prior to the Screening Visit will be acceptable for study entry. Transient previous use of corticosteroids will be evaluated on a case-by-case basis by the sponsor or designee. The use of topical or intra-articular corticosteroids is permitted during the study Participant is unable to complete the 10 meter Walk/Run test at the Screening and/or Baseline Visit. Participant has Type 1 or Type 2 diabetes mellitus. Participant has a history of chronic active hepatitis including acute or chronic hepatitis B, or acute or chronic hepatitis C. Participant has a history of tuberculosis (TB) infection, any signs/symptoms of TB, or any close contact with an individual with an active TB infection. Participant has known immune compromised status (not related to disease/condition under study), including but not limited to, individuals who have undergone organ transplantation or who are known to be positive for the human immunodeficiency virus.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 8 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: Parallel Assignment
Interventional Model Description: In the double-blind period, participants are randomized to receive study drug or placebo. It is followed by an open label period wherein all participants receive study drug.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 1: MNK-1411<br>Participants receive MNK-1411 at a dosing volume appropriate to body weight during Period 1 | Drug: MNK-1411<br>* MNK-1411 (1 mg/mL suspension) for subcutaneous injection<br>* Other names: Tetracosactide Hexaacetate;|
| Experimental: Period 1: Placebo<br>Participants receive placebo at a volume appropriate to body weight during Period 1 | Other: Placebo<br>* Placebo suspension for subcutaneous injection<br>* Other names: Matching Placebo;|
| Experimental: Period 2: MNK-1411<br>All participants receive MNK-1411 at a dosing volume appropriate to body weight during Period 2 | Drug: MNK-1411<br>* MNK-1411 (1 mg/mL suspension) for subcutaneous injection<br>* Other names: Tetracosactide Hexaacetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Complete 10 Meter Walk/Run[ | 10 Meter Walk/Run is a motor function test to measure the functional capability in patients with DMD. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| North Star Ambulatory Assessment (NSAA) Score | The NSAA is comprised of 17 items, each of which is graded using the standard scorecard. Each assessment is rated as 0 - unable to achieve independently, 1 - modified method but achieves goal independent of physical assistance from another, or 2 - normal with no obvious modification of activity. The subscale scores are summed for a total score ranging from 0 to 34. The higher the total score, the better the outcome. | Baseline, Week 24 | 
| Time to Climb 4 Standardized Stairs | Time to Climb 4 Standardized Stairs is a motor performance test | Baseline, Week 24 | 
| Time to Stand From a Supine Position | Time to stand from a supine position is a motor function test to measure the functional capability in subjects with DMD. | Baseline, Week 24 | 
| Quantitative Muscle Testing Scores at Baseline | Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer | Baseline | 
| Quantitative Muscle Testing Scores at Week 24 | Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer | Week 24 | 
| Summary of Adverse Events in the Blinded Treatment Period | Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessments were reported as adverse events (AEs) | within 28 weeks | 
| Summary of Adverse Events in the Open Label Period | Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessments were reported as adverse events (AEs) | within 28 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Muscular Dystrophy, DMD, Duchenne