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

Mallinckrodt

Status and phase: Terminated; Phase 2

Conditions: Muscular Dystrophy, Duchenne

Treatments: Other: Placebo; Drug: MNK-1411

Study type: Interventional

Funder types: Industry

Identifiers

NCT03400852

MNK14112096

2017-004139-35 (EudraCT Number)

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 44 patients

Sex: Male

Ages: 4 to 8 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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.
2. 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

1. 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
2. Participant is unable to complete the 10 meter Walk/Run test at the Screening and/or Baseline Visit.
3. Participant has Type 1 or Type 2 diabetes mellitus.
4. Participant has a history of chronic active hepatitis including acute or chronic hepatitis B, or acute or chronic hepatitis C.
5. 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.
6. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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44 participants in 3 patient groups

Period 1: MNK-1411

Experimental group

Description:

Participants receive MNK-1411 at a dosing volume appropriate to body weight during Period 1

Treatment:

Drug: MNK-1411

Period 1: Placebo

Experimental group

Description:

Participants receive placebo at a volume appropriate to body weight during Period 1

Treatment:

Other: Placebo

Period 2: MNK-1411

Experimental group

Description:

All participants receive MNK-1411 at a dosing volume appropriate to body weight during Period 2

Treatment:

Drug: MNK-1411