Back to resultsA Study to Assess the Efficacy and Safety of MNK-1411 in Duchenne Muscular Dystrophy (BRAVE)
Primary Purpose
Muscular Dystrophy, Duchenne
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MNK-1411
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Muscular Dystrophy, Duchenne focused on measuring Muscular Dystrophy, DMD, Duchenne
Eligibility Criteria
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.
Sites / Locations
- NW FL Clinical Research Group, LLC
- Rare Disease Research, LLC
- Monroe Carell Jr Childrens Hospital at Vanderbilt
- University of Texas Southwestern Medical Center
- UT Health Science Center, San Antonio
- University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
- Edith Wolfson Medical Center
- Ospedale San Raffaele S.r.l. - PPDS
- Hospital Civil Fray Antonio Alcalde
- Neurociencias Estudios Clinicos S.C.
- Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
- Clinic of Neurology and Psychiatry for Children and Youth
- Hospital de La Santa Creu i Sant Pau
- Hospital Sant Joan de Deu - PIN
- Hospital Universitari i Politecnic La Fe Valencia
- Mersin Universitesi Tip Fakultesi Hastanesi
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Period 1: MNK-1411
Period 1: Placebo
Period 2: MNK-1411
Arm Description
Participants receive MNK-1411 at a dosing volume appropriate to body weight during Period 1
Participants receive placebo at a volume appropriate to body weight during Period 1
All participants receive MNK-1411 at a dosing volume appropriate to body weight during Period 2
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Time to Climb 4 Standardized Stairs
Time to Climb 4 Standardized Stairs is a motor performance test
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.
Quantitative Muscle Testing Scores at Baseline
Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer
Quantitative Muscle Testing Scores at Week 24
Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer
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)
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)
Full Information
NCT ID
NCT03400852
First Posted
January 9, 2018
Last Updated
February 19, 2021
Sponsor
Mallinckrodt ARD LLC
1. Study Identification
Unique Protocol Identification Number
NCT03400852
Brief Title
A Study to Assess the Efficacy and Safety of MNK-1411 in Duchenne Muscular Dystrophy
Acronym
BRAVE
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
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
Slow enrollment
Study Start Date
July 27, 2018 (Actual)
Primary Completion Date
February 25, 2020 (Actual)
Study Completion Date
February 25, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mallinckrodt ARD LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Dystrophy, Duchenne
Keywords
Muscular Dystrophy, DMD, Duchenne
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantInvestigator
Masking Description
Double blind (Investigator/Participant) The Care Provider and Outcomes Assessor were also blinded, but it is a double-blind trial, followed by an open-label period.
Allocation
Randomized
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Period 1: MNK-1411
Arm Type
Experimental
Arm Description
Participants receive MNK-1411 at a dosing volume appropriate to body weight during Period 1
Arm Title
Period 1: Placebo
Arm Type
Experimental
Arm Description
Participants receive placebo at a volume appropriate to body weight during Period 1
Arm Title
Period 2: MNK-1411
Arm Type
Experimental
Arm Description
All participants receive MNK-1411 at a dosing volume appropriate to body weight during Period 2
Intervention Type
Drug
Intervention Name(s)
MNK-1411
Other Intervention Name(s)
Cosyntropin acetate, Tetracosactide Hexaacetate
Intervention Description
MNK-1411 (1 mg/mL suspension) for subcutaneous injection
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
Matching Placebo
Intervention Description
Placebo suspension for subcutaneous injection
Primary Outcome Measure Information:
Title
Time to Complete 10 Meter Walk/Run[
Description
10 Meter Walk/Run is a motor function test to measure the functional capability in patients with DMD.
Time Frame
Baseline, Week 24
Secondary Outcome Measure Information:
Title
North Star Ambulatory Assessment (NSAA) Score
Description
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.
Time Frame
Baseline, Week 24
Title
Time to Climb 4 Standardized Stairs
Description
Time to Climb 4 Standardized Stairs is a motor performance test
Time Frame
Baseline, Week 24
Title
Time to Stand From a Supine Position
Description
Time to stand from a supine position is a motor function test to measure the functional capability in subjects with DMD.
Time Frame
Baseline, Week 24
Title
Quantitative Muscle Testing Scores at Baseline
Description
Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer
Time Frame
Baseline
Title
Quantitative Muscle Testing Scores at Week 24
Description
Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer
Time Frame
Week 24
Title
Summary of Adverse Events in the Blinded Treatment Period
Description
Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessments were reported as adverse events (AEs)
Time Frame
within 28 weeks
Title
Summary of Adverse Events in the Open Label Period
Description
Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessments were reported as adverse events (AEs)
Time Frame
within 28 weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
8 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Study Lead
Organizational Affiliation
Mallinckrodt
Official's Role
Study Director
Facility Information:
Facility Name
NW FL Clinical Research Group, LLC
City
Gulf Breeze
State/Province
Florida
ZIP/Postal Code
32561
Country
United States
Facility Name
Rare Disease Research, LLC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
Monroe Carell Jr Childrens Hospital at Vanderbilt
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75207
Country
United States
Facility Name
UT Health Science Center, San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
Edith Wolfson Medical Center
City
H̱olon
ZIP/Postal Code
5810001
Country
Israel
Facility Name
Ospedale San Raffaele S.r.l. - PPDS
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20132
Country
Italy
Facility Name
Hospital Civil Fray Antonio Alcalde
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
44280
Country
Mexico
Facility Name
Neurociencias Estudios Clinicos S.C.
City
Culiacán
State/Province
Sinaloa
ZIP/Postal Code
80020
Country
Mexico
Facility Name
Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
City
Durango
ZIP/Postal Code
34000
Country
Mexico
Facility Name
Clinic of Neurology and Psychiatry for Children and Youth
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Hospital de La Santa Creu i Sant Pau
City
Barcelona
ZIP/Postal Code
08025
Country
Spain
Facility Name
Hospital Sant Joan de Deu - PIN
City
Esplugues De Llobregat
ZIP/Postal Code
08950
Country
Spain
Facility Name
Hospital Universitari i Politecnic La Fe Valencia
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Mersin Universitesi Tip Fakultesi Hastanesi
City
Mersin
ZIP/Postal Code
33343
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Discussion of statistical endpoints and analysis are included in manuscripts. Summary aggregate (basic) results (including adverse events information) and the study protocol are made available on clinicaltrials.gov (NCT03400852) when required by regulation. Individual de-identified patient data will not be disclosed. Requests for additional information should be directed to the company at medinfo@mnk.com.
Learn more about this trial
A Study to Assess the Efficacy and Safety of MNK-1411 in Duchenne Muscular Dystrophy
We'll reach out to this number within 24 hrs