TerminatedNCT03400852BRAVEUpdated Mar 16, 2021Results posted

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

A Phase 2 interventional study of MNK-1411 and Placebo in Muscular Dystrophy, Duchenne, sponsored by Mallinckrodt ARD LLC. Terminated at 16 sites in 8 countries. Open to male participants aged 4 Years to 8 Years. Per ClinicalTrials.gov, last updated 2021-03-16.

Sponsored by Mallinckrodt ARD LLC · Phase 2, Interventional, and Treatment

Why this study was terminated

Slow enrollment

Phase: Phase 2
Study type: Interventional
Enrollment: 44
Allocation: Randomized
Ages: 4 Years to 8 Years
Sex: Male

Study 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).

Read the 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.

Conditions studied

Muscular Dystrophy, Duchenne

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Keywords

Muscular Dystrophy
DMD
Duchenne

Who can participate

Ages eligible: 4 Years to 8 Years
Sexes eligible: Male
Accepts healthy volunteers: No

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

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.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 44 participants (actual)

Study arms

Experimental
Period 1: MNK-1411
Participants receive MNK-1411 at a dosing volume appropriate to body weight during Period 1
Drug: MNK-1411
Experimental
Period 1: Placebo
Participants receive placebo at a volume appropriate to body weight during Period 1
Other: Placebo
Experimental
Period 2: MNK-1411
All participants receive MNK-1411 at a dosing volume appropriate to body weight during Period 2
Drug: MNK-1411

Interventions

DrugMNK-1411
MNK-1411 (1 mg/mL suspension) for subcutaneous injection
Also known as: Cosyntropin acetate, Tetracosactide Hexaacetate
OtherPlacebo
Placebo suspension for subcutaneous injection
Also known as: Matching Placebo

What researchers measure

Primary outcomes

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.
Time frame: Baseline, Week 24

Secondary outcomes

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 frame: Baseline, Week 24
Time to Climb 4 Standardized Stairs
Time to Climb 4 Standardized Stairs is a motor performance test
Time frame: 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.
Time frame: Baseline, Week 24
Quantitative Muscle Testing Scores at Baseline
Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer
Time frame: Baseline
Quantitative Muscle Testing Scores at Week 24
Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer
Time frame: 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)
Time frame: 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)
Time frame: within 28 weeks

Results

Posted Feb 21, 2021

Participant flow

Twenty-four participants with Duchenne Muscular Dystrophy (DMD) who chose to discontinue the double-blind period prior to Week 24 entered the open label extension (OLE, Period 2). Participants who did not enter OLE Period were followed up to Week 28.

Blinded Treatment Period

Participant flow — Blinded Treatment Period
Milestone	Period 1: MNK-1411	Period 1: Placebo
Started	29	15
Completed	20	9
Not completed	9	6
Withdrew: Physician decision	0	1
Withdrew: Adverse event	1	1
Withdrew: Study terminated by sponsor	8	4

Open Label Period

Participant flow — Open Label Period
Milestone	Period 1: MNK-1411	Period 1: Placebo	Period 2: MNK-1411
Started	0	0	24
Completed	0	0	2
Not completed	0	0	22
Withdrew: Physician decision	0	0	1
Withdrew: Study terminated by sponsor	0	0	21

Outcome measures

PrimaryTime to Complete 10 Meter Walk/Run[

10 Meter Walk/Run is a motor function test to measure the functional capability in patients with DMD.

Time frame:: Baseline, Week 24
Reported as:: Median · seconds

Time to Complete 10 Meter Walk/Run[
seconds	Period 1: MNK-1411	Period 1: Placebo
at Baseline	5.9 (4.7 to 22.3)	7.8 (3.9 to 13.0)
at Week 24	5.4 (4.1 to 8.9)	8.7 (3.3 to 18.3)

SecondaryNorth 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 frame:: Baseline, Week 24
Reported as:: Mean · score on a scale

North Star Ambulatory Assessment (NSAA) Score
score on a scale	Period 1: MNK-1411	Period 1: Placebo
at Baseline	17.9 ± 6.80	17.1 ± 6.40
at Week 24	20.5 ± 7.94	16.6 ± 8.82

SecondaryTime to Climb 4 Standardized Stairs

Time to Climb 4 Standardized Stairs is a motor performance test

Time frame:: Baseline, Week 24
Reported as:: Mean · seconds

Time to Climb 4 Standardized Stairs
seconds	Period 1: MNK-1411	Period 1: Placebo
at Baseline	8.52 ± 8.88	8.47 ± 4.34
at Week 24	4.71 ± 2.45	15.09 ± 13.84

SecondaryTime 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.

Time frame:: Baseline, Week 24
Reported as:: Mean · seconds

Time to Stand From a Supine Position
seconds	Period 1: MNK-1411	Period 1: Placebo
at Baseline	11.14 ± 9.08	15.03 ± 12.45
at Week 24	7.65 ± 4.99	24.89 ± 26.48

SecondaryQuantitative Muscle Testing Scores at Baseline

Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer

Time frame:: Baseline
Reported as:: Mean · Newtons

Quantitative Muscle Testing Scores at Baseline
Newtons	Period 1: MNK-1411	Period 1: Placebo
Knee flexion	26.61 ± 14.17	29.87 ± 14.17
Knee extension	28.99 ± 16.24	26.64 ± 15.27

SecondaryQuantitative Muscle Testing Scores at Week 24

Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer

Time frame:: Week 24
Reported as:: Mean · Newtons

Quantitative Muscle Testing Scores at Week 24
Newtons	Period 1: MNK-1411	Period 1: Placebo
Knee flexion	33.64 ± 1578	25.27 ± 13.35
Knee extension	26.61 ± 14.17	29.87 ± 15.13

SecondarySummary 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)

Time frame:: within 28 weeks
Reported as:: Count of participants · Participants

Summary of Adverse Events in the Blinded Treatment Period
Participants	Period 1: MNK-1411	Period 1: Placebo
Exposed	29	15
Affected by serious adverse events	0	1
Affected by non-serious adverse events	22	15
Died from any cause	0	0

SecondarySummary 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)

Time frame:: within 28 weeks
Reported as:: Count of participants · Participants

Summary of Adverse Events in the Open Label Period
Participants	Period 2: MNK-1411
Exposed	24
Affected by serious adverse events	2
Affected by non-serious adverse events	11
Died from any cause	0

Adverse events

Collected over within 28 weeks. Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Period 1: MNK-1411	0/29 (0%)	0/29 (0%)	22/29 (75.9%)
Period 1: Placebo	0/15 (0%)	1/15 (6.7%)	15/15 (100%)
Period 2: MNK-1411	0/24 (0%)	2/24 (8.3%)	11/24 (45.8%)

Most frequent serious events

Most frequent serious events
Event	Period 1: MNK-1411	Period 1: Placebo	Period 2: MNK-1411
Muscle disorderMusculoskeletal and connective tissue disorders	0/29	1/15	0/24
RhabdomyolysisMusculoskeletal and connective tissue disorders	0/29	0/15	1/24
nary tract infectionInfections and infestations	0/29	0/15	1/24

Most frequent other events

Showing 10 of 77

Most frequent other events
Event	Period 1: MNK-1411	Period 1: Placebo	Period 2: MNK-1411
Weight increasedInvestigations	7/29	0/15	3/24
Injection site massGeneral disorders	1/29	3/15	1/24
GastroenteritisInfections and infestations	0/29	3/15	1/24
Injection site erythemaGeneral disorders	4/29	1/15	1/24
Injection site indurationGeneral disorders	4/29	1/15	2/24
Face oedemaGeneral disorders	1/29	2/15	0/24
PyrexiaGeneral disorders	1/29	2/15	1/24
CoughRespiratory, thoracic and mediastinal disorders	2/29	2/15	0/24
PharyngitisInfections and infestations	0/29	2/15	0/24
Upper respiratory tract infectionInfections and infestations	1/29	2/15	1/24

Baseline characteristics

All participants enrolled into the study.

Age, Customized
Age, Customized(Participants)	Period 1: MNK-1411	Period 1: Placebo	Total
Children (2-11 Years)	29	15	44

Sex: Female, Male
Sex: Female, Male(Participants)	Period 1: MNK-1411	Period 1: Placebo	Total
Female	0	0	0
Male	29	15	44

Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)	Period 1: MNK-1411	Period 1: Placebo	Total
Count of participants	—	—	0

Region of Enrollment
Region of Enrollment(participants)	Period 1: MNK-1411	Period 1: Placebo	Total
Turkey	0	0	3
United States	0	0	10
Italy	0	0	2
Mexico	0	0	18
Israel	0	0	1
Bulgaria	0	0	2
Serbia	0	0	2
Spain	0	0	6

Study locations

16 sites

NW FL Clinical Research Group, LLC
Gulf Breeze, Florida 32561, United States
Rare Disease Research, LLC
Atlanta, Georgia 30318, United States
Monroe Carell Jr Childrens Hospital at Vanderbilt
Nashville, Tennessee 37232, United States
University of Texas Southwestern Medical Center
Dallas, Texas 75207, United States
UT Health Science Center, San Antonio
San Antonio, Texas 78229, United States
University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
Sofia, 1431, Bulgaria
Edith Wolfson Medical Center
H̱olon, 5810001, Israel
Ospedale San Raffaele S.r.l. - PPDS
Milano, Lombardia 20132, Italy
Hospital Civil Fray Antonio Alcalde
Guadalajara, Jalisco 44280, Mexico
Neurociencias Estudios Clinicos S.C.
Culiacán, Sinaloa 80020, Mexico
Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
Durango, 34000, Mexico
Clinic of Neurology and Psychiatry for Children and Youth
Belgrade, 11000, Serbia
Hospital de La Santa Creu i Sant Pau
Barcelona, 08025, Spain
Hospital Sant Joan de Deu - PIN
Esplugues De Llobregat, 08950, Spain
Hospital Universitari i Politecnic La Fe Valencia
Valencia, 46026, Spain
Mersin Universitesi Tip Fakultesi Hastanesi
Mersin, 33343, Turkey

References and documents

Study documents

Protocol and statistical analysis plan · May 23, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — 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.

Registry details

Key details

Study ID: NCT03400852
Lead sponsor: Mallinckrodt ARD LLC
Responsible party: Sponsor
First posted: Jan 17, 2018
Start date: Jul 27, 2018
Primary completion: Feb 25, 2020
Completion: Feb 25, 2020
Results posted: Feb 21, 2021
Last update: Mar 16, 2021

Study contacts

Clinical Study Lead

study director · Mallinckrodt

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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