Clinical trial NCT03400852: A Study to Assess the Efficacy and Safety of MNK-1411 in Duchenne Muscular Dystrophy
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Muscular Dystrophy, Duchenne
Keywords: Muscular Dystrophy
DMD
Duchenne
Lead sponsor: Mallinckrodt
Sponsor class: INDUSTRY
First posted: 2018-01-17
Enrollment: 44
Sex: MALE
Minimum age (years): 4
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Time to Complete 10 Meter Walk/Run[
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: North Star Ambulatory Assessment (NSAA) Score
timeFrame: Baseline, Week 24
measure: Time to Climb 4 Standardized Stairs
timeFrame: Baseline, Week 24
measure: Time to Stand From a Supine Position
timeFrame: Baseline, Week 24
measure: Quantitative Muscle Testing Scores at Baseline
timeFrame: Baseline
measure: Quantitative Muscle Testing Scores at Week 24
timeFrame: Week 24
measure: Summary of Adverse Events in the Blinded Treatment Period
timeFrame: within 28 weeks
measure: Summary of Adverse Events in the Open Label Period
timeFrame: within 28 weeks
Other outcomes:
Locations:
city: Gulf Breeze
country: United States
facility: NW FL Clinical Research Group, LLC
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research, LLC
state: Georgia
city: Nashville
country: United States
facility: Monroe Carell Jr Childrens Hospital at Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: San Antonio
country: United States
facility: UT Health Science Center, San Antonio
state: Texas
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
city: H̱olon
country: Israel
facility: Edith Wolfson Medical Center
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l. - PPDS
state: Lombardia
city: Guadalajara
country: Mexico
facility: Hospital Civil Fray Antonio Alcalde
state: Jalisco
city: Culiacán
country: Mexico
facility: Neurociencias Estudios Clinicos S.C.
state: Sinaloa
city: Durango
country: Mexico
facility: Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
city: Belgrade
country: Serbia
facility: Clinic of Neurology and Psychiatry for Children and Youth
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Esplugues De Llobregat
country: Spain
facility: Hospital Sant Joan de Deu - PIN
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe Valencia
city: Mersin
country: Turkey
facility: Mersin Universitesi Tip Fakultesi Hastanesi
Study officials:
affiliation: Mallinckrodt
name: Clinical Study Lead
role: STUDY_DIRECTOR
References: