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Trial record 1 of 1 for:    MNK-1411 | Duchenne Muscular Dystrophy
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A Study to Assess the Efficacy and Safety of MNK-1411 in Duchenne Muscular Dystrophy (BRAVE)

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ClinicalTrials.gov Identifier: NCT03400852
Recruitment Status : Terminated (Slow enrollment)
First Posted : January 17, 2018
Results First Posted : February 21, 2021
Last Update Posted : March 16, 2021
Sponsor:
Information provided by (Responsible Party):
Mallinckrodt ( Mallinckrodt ARD LLC )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Muscular Dystrophy, Duchenne
Interventions Drug: MNK-1411
Other: Placebo
Enrollment 44
Recruitment Details 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.
Pre-assignment Details After screening, 44 participants from 8 countries were enrolled into Period 1
Arm/Group Title Period 1: MNK-1411 Period 1: Placebo Period 2: MNK-1411
Hide Arm/Group 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
Period Title: Blinded Treatment Period
Started [1] 29 15 0
Completed 20 9 0
Not Completed 9 6 0
Reason Not Completed
Physician Decision             0             1             0
Adverse Event             1             1             0
Study terminated by sponsor             8             4             0
[1]
Period 2 arm not included in Period 1
Period Title: Open Label Period
Started [1] 0 0 24
Completed 0 0 2
Not Completed 0 0 22
Reason Not Completed
Physician Decision             0             0             1
Study terminated by sponsor             0             0             21
[1]
Period 1 arms not included in Period 2
Arm/Group Title Period 1: MNK-1411 Period 1: Placebo Total
Hide Arm/Group Description All participants who received any dose of MNK-1411 in Period 1 All patients who received placebo in Period 1 Total of all reporting groups
Overall Number of Baseline Participants 29 15 44
Hide Baseline Analysis Population Description
All participants enrolled into the study.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Children (2-11 Years) Number Analyzed 29 participants 15 participants 44 participants
29
 100.0%
15
 100.0%
44
 100.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 15 participants 44 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
Male
29
 100.0%
15
 100.0%
44
 100.0%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants
0
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Turkey Number Analyzed 29 participants 15 participants 44 participants
0 0 3
United States Number Analyzed 29 participants 15 participants 44 participants
0 0 10
Italy Number Analyzed 29 participants 15 participants 44 participants
0 0 2
Mexico Number Analyzed 29 participants 15 participants 44 participants
0 0 18
Israel Number Analyzed 29 participants 15 participants 44 participants
0 0 1
Bulgaria Number Analyzed 29 participants 15 participants 44 participants
0 0 2
Serbia Number Analyzed 29 participants 15 participants 44 participants
0 0 2
Spain Number Analyzed 29 participants 15 participants 44 participants
0 0 6
[1]
Measure Description: Region was recorded for the total number of participants enrolled, not broken down into randomized groups.
1.Primary Outcome
Title Time to Complete 10 Meter Walk/Run[
Hide Description 10 Meter Walk/Run is a motor function test to measure the functional capability in patients with DMD.
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Summary aggregate results for all participants enrolled into Period 1 and with a score at Week 24
Arm/Group Title Period 1: MNK-1411 Period 1: Placebo
Hide Arm/Group Description:
All participants who received any dose of MNK-1411 in Period 1
All patients who received placebo in Period 1
Overall Number of Participants Analyzed 29 15
Median (Full Range)
Unit of Measure: seconds
at Baseline Number Analyzed 29 participants 15 participants
5.9
(4.7 to 22.3)
7.8
(3.9 to 13.0)
at Week 24 Number Analyzed 16 participants 9 participants
5.4
(4.1 to 8.9)
8.7
(3.3 to 18.3)
2.Secondary Outcome
Title North Star Ambulatory Assessment (NSAA) Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Summary aggregate results for all participants enrolled into Period 1 and with a score at Week 24
Arm/Group Title Period 1: MNK-1411 Period 1: Placebo
Hide Arm/Group Description:
All participants who received any dose of MNK-1411 in Period 1
All patients who received placebo in Period 1
Overall Number of Participants Analyzed 29 15
Mean (Standard Deviation)
Unit of Measure: score on a scale
at Baseline Number Analyzed 29 participants 15 participants
17.9  (6.80) 17.1  (6.40)
at Week 24 Number Analyzed 17 participants 9 participants
20.5  (7.94) 16.6  (8.82)
3.Secondary Outcome
Title Time to Climb 4 Standardized Stairs
Hide Description Time to Climb 4 Standardized Stairs is a motor performance test
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Summary aggregate results for all participants enrolled into Period 1 and with a score at Week 24
Arm/Group Title Period 1: MNK-1411 Period 1: Placebo
Hide Arm/Group Description:
All participants who received any dose of MNK-1411 in Period 1
All patients who received placebo in Period 1
Overall Number of Participants Analyzed 29 15
Mean (Standard Deviation)
Unit of Measure: seconds
at Baseline Number Analyzed 29 participants 15 participants
8.52  (8.88) 8.47  (4.34)
at Week 24 Number Analyzed 15 participants 9 participants
4.71  (2.45) 15.09  (13.84)
4.Secondary Outcome
Title Time to Stand From a Supine Position
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Summary aggregate results for all participants who enrolled into Period 1 with a score for this measure at the given time point
Arm/Group Title Period 1: MNK-1411 Period 1: Placebo
Hide Arm/Group Description:
All participants who received any dose of MNK-1411 in Period 1
All patients who received placebo in Period 1
Overall Number of Participants Analyzed 23 13
Mean (Standard Deviation)
Unit of Measure: seconds
at Baseline Number Analyzed 23 participants 13 participants
11.14  (9.08) 15.03  (12.45)
at Week 24 Number Analyzed 16 participants 9 participants
7.65  (4.99) 24.89  (26.48)
5.Secondary Outcome
Title Quantitative Muscle Testing Scores at Baseline
Hide Description Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Summary aggregate results for all participants enrolled into Period 1 with a score at baseline.
Arm/Group Title Period 1: MNK-1411 Period 1: Placebo
Hide Arm/Group Description:
All participants who received any dose of MNK-1411 in Period 1
All patients who received placebo in Period 1
Overall Number of Participants Analyzed 25 15
Mean (Standard Deviation)
Unit of Measure: Newtons
Knee flexion 26.61  (14.17) 29.87  (14.17)
Knee extension 28.99  (16.24) 26.64  (15.27)
6.Secondary Outcome
Title Quantitative Muscle Testing Scores at Week 24
Hide Description Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Summary aggregate results for all participants enrolled into Period 1 with a score at Week 24
Arm/Group Title Period 1: MNK-1411 Period 1: Placebo
Hide Arm/Group Description:
All participants who received any dose of MNK-1411 in Period 1
All patients who received placebo in Period 1
Overall Number of Participants Analyzed 18 9
Mean (Standard Deviation)
Unit of Measure: Newtons
Knee flexion 33.64  (1578) 25.27  (13.35)
Knee extension 26.61  (14.17) 29.87  (15.13)
7.Secondary Outcome
Title Summary of Adverse Events in the Blinded Treatment Period
Hide Description Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessments were reported as adverse events (AEs)
Time Frame within 28 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Summary aggregate results for all participants enrolled into Period 1
Arm/Group Title Period 1: MNK-1411 Period 1: Placebo
Hide Arm/Group Description:
All participants who received any dose of MNK-1411 in Period 1
All patients who received placebo in Period 1
Overall Number of Participants Analyzed 29 15
Measure Type: Count of Participants
Unit of Measure: Participants
Exposed
29
 100.0%
15
 100.0%
Affected by serious adverse events
0
   0.0%
1
   6.7%
Affected by non-serious adverse events
22
  75.9%
15
 100.0%
Died from any cause
0
   0.0%
0
   0.0%
8.Secondary Outcome
Title Summary of Adverse Events in the Open Label Period
Hide Description Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessments were reported as adverse events (AEs)
Time Frame within 28 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Summary aggregate results for all participants enrolled into Period 2
Arm/Group Title Period 2: MNK-1411
Hide Arm/Group Description:
All participants who received any dose of MNK-1411 in Period 2
Overall Number of Participants Analyzed 24
Measure Type: Count of Participants
Unit of Measure: Participants
Exposed
24
 100.0%
Affected by serious adverse events
2
   8.3%
Affected by non-serious adverse events
11
  45.8%
Died from any cause
0
   0.0%
Time Frame within 28 weeks
Adverse Event Reporting Description Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessment were reported as AEs
 
Arm/Group Title Period 1: MNK-1411 Period 1: Placebo Period 2: MNK-1411
Hide Arm/Group 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 Participants receive MNK-1411 at a dosing volume appropriate to body weight during Period 2
All-Cause Mortality
Period 1: MNK-1411 Period 1: Placebo Period 2: MNK-1411
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/29 (0.00%)      0/15 (0.00%)      0/24 (0.00%)    
Hide Serious Adverse Events
Period 1: MNK-1411 Period 1: Placebo Period 2: MNK-1411
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/29 (0.00%)      1/15 (6.67%)      2/24 (8.33%)    
Infections and infestations       
nary tract infection  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
Musculoskeletal and connective tissue disorders       
Muscle disorder  1  0/29 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Rhabdomyolysis  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
1
Term from vocabulary, MedDRA (22.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Period 1: MNK-1411 Period 1: Placebo Period 2: MNK-1411
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/29 (75.86%)      15/15 (100.00%)      11/24 (45.83%)    
Blood and lymphatic system disorders       
Leukocytosis  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
Cardiac disorders       
Congestive cardiomyopathy  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
Sinus tachycardia  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  2
Endocrine disorders       
Cushing's syndrome  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Cushingoid  1  2/29 (6.90%)  2 0/15 (0.00%)  0 0/24 (0.00%)  0
Gastrointestinal disorders       
Abdominal distension  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Abdominal pain  1  2/29 (6.90%)  2 0/15 (0.00%)  0 0/24 (0.00%)  0
Aphthous ulcer  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Diarrhoea  1  1/29 (3.45%)  2 0/15 (0.00%)  0 1/24 (4.17%)  1
Food poisoning  1  1/29 (3.45%)  1 1/15 (6.67%)  1 0/24 (0.00%)  0
Irritable bowel syndrome  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Vomiting  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
General disorders       
Face oedema  1  1/29 (3.45%)  1 2/15 (13.33%)  2 0/24 (0.00%)  0
Fatigue  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Injection site bruising  1  1/29 (3.45%)  1 1/15 (6.67%)  1 0/24 (0.00%)  0
Injection site erythema  1  4/29 (13.79%)  4 1/15 (6.67%)  1 1/24 (4.17%)  1
Injection site haematoma  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Injection site haemorrhage  1  0/29 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Injection site induration  1  4/29 (13.79%)  4 1/15 (6.67%)  1 2/24 (8.33%)  2
Injection site irritation  1  0/29 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Injection site mass  1  1/29 (3.45%)  1 3/15 (20.00%)  3 1/24 (4.17%)  1
Injection site pain  1  2/29 (6.90%)  2 1/15 (6.67%)  1 0/24 (0.00%)  0
Injection site swelling  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Pyrexia  1  1/29 (3.45%)  1 2/15 (13.33%)  2 1/24 (4.17%)  1
Swelling face  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Immune system disorders       
Allergy to arthropod bite  1  0/29 (0.00%)  0 1/15 (6.67%)  2 1/24 (4.17%)  2
Infections and infestations       
Bronchitis  1  0/29 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Ear infection  1  0/29 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Gastroenteritis  1  0/29 (0.00%)  0 3/15 (20.00%)  4 1/24 (4.17%)  1
Nasopharyngitis  1  2/29 (6.90%)  2 1/15 (6.67%)  1 1/24 (4.17%)  1
Gastroenteritis viral  1  2/29 (6.90%)  2 0/15 (0.00%)  0 0/24 (0.00%)  0
Influenza  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Enterobiasis  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
Otitis media acute  1  0/29 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Pharyngitis  1  0/29 (0.00%)  0 2/15 (13.33%)  2 0/24 (0.00%)  0
Pharyngotonsillitis  1  3/29 (10.34%)  3 0/15 (0.00%)  0 0/24 (0.00%)  0
Scarlet fever  1  0/29 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Tonsillitis bacterial  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Tooth abscess  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Upper respiratory tract infection  1  1/29 (3.45%)  1 2/15 (13.33%)  2 1/24 (4.17%)  1
Urinary tract infection  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Viral infection  1  0/29 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Viral pharyngitis  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Oral herpes  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
Otitis media  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
Upper respiratory tract infection bacterial  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
Injury, poisoning and procedural complications       
Lower limb fracture  1  0/29 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Investigations       
Weight increased  1  7/29 (24.14%)  9 0/15 (0.00%)  0 3/24 (12.50%)  3
Nerve stimulation test abnormal  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
Metabolism and nutrition disorders       
Hyperglycaemia  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Hyperphagia  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Increased appetite  1  1/29 (3.45%)  1 0/15 (0.00%)  0 1/24 (4.17%)  1
Hypokalaemia  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
Musculoskeletal and connective tissue disorders       
Muscle spasms  1  1/29 (3.45%)  2 0/15 (0.00%)  0 0/24 (0.00%)  0
Myalgia  1  0/29 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Nervous system disorders       
Headache  1  2/29 (6.90%)  2 0/15 (0.00%)  0 0/24 (0.00%)  0
Motor dysfunction  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Psychomotor hyperactivity  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
Psychiatric disorders       
Affect lability  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Depression  1  1/29 (3.45%)  1 1/15 (6.67%)  1 0/24 (0.00%)  0
Mood swings  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Separation anxiety disorder  1  0/29 (0.00%)  0 1/15 (6.67%)  1 1/24 (4.17%)  1
Renal and urinary disorders       
Proteinuria  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Glycosuria  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  3
Respiratory, thoracic and mediastinal disorders       
Bronchial hyperreactivity  1  0/29 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Cough  1  2/29 (6.90%)  3 2/15 (13.33%)  2 0/24 (0.00%)  0
Oropharyngeal pain  1  0/29 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Asthma  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
Skin and subcutaneous tissue disorders       
Acne  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Erythema  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Hirsutism  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Hypertrichosis  1  2/29 (6.90%)  2 0/15 (0.00%)  0 0/24 (0.00%)  0
Seborrhoeic dermatitis  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Swelling face  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Lipohypertrophy  1  0/29 (0.00%)  0 0/15 (0.00%)  0 1/24 (4.17%)  1
Vascular disorders       
Haematoma  1  1/29 (3.45%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Hypertension  1  1/29 (3.45%)  1 0/15 (0.00%)  0 1/24 (4.17%)  2
1
Term from vocabulary, MedDRA (22.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Information Call Center
Organization: Mallinckrodt
Phone: 1-800-844-2830
EMail: MedInfo@mnk.com
Layout table for additonal information
Responsible Party: Mallinckrodt ( Mallinckrodt ARD LLC )
ClinicalTrials.gov Identifier: NCT03400852    
Other Study ID Numbers: MNK14112096
2017-004139-35 ( EudraCT Number )
First Submitted: January 9, 2018
First Posted: January 17, 2018
Results First Submitted: February 2, 2021
Results First Posted: February 21, 2021
Last Update Posted: March 16, 2021