Muscular Dystrophy, Duchenne
Conditions
Keywords
Muscular Dystrophy, DMD, Duchenne
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.
Interventions
DRUGMNK-1411
MNK-1411 (1 mg/mL suspension) for subcutaneous injection
OTHERPlacebo
Placebo suspension for subcutaneous injection
Sponsors
Mallinckrodt ARD LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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.
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.
Eligibility
Sex/Gender
MALE
Age
4 Years to 8 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Complete 10 Meter Walk/Run[ | Baseline, Week 24 | 10 Meter Walk/Run is a motor function test to measure the functional capability in patients with DMD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Climb 4 Standardized Stairs | Baseline, Week 24 | Time to Climb 4 Standardized Stairs is a motor performance test |
| Time to Stand From a Supine Position | Baseline, Week 24 | 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 | Baseline | Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer |
| North Star Ambulatory Assessment (NSAA) Score | Baseline, Week 24 | 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. |
| Summary of Adverse Events in the Blinded Treatment Period | within 28 weeks | 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 | within 28 weeks | Clinically significant changes in vital signs, height, weight, immunogenicity and laboratory assessments were reported as adverse events (AEs) |
| Quantitative Muscle Testing Scores at Week 24 | Week 24 | Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer |
Countries
Bulgaria, Israel, Italy, Mexico, Serbia, Spain, Turkey (Türkiye), United States
Participant flow
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
Participants by arm
| Arm | Count |
|---|---|
| Period 1: MNK-1411 All participants who received any dose of MNK-1411 in Period 1 | 29 |
| Period 1: Placebo All patients who received placebo in Period 1 | 15 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Blinded Treatment Period | Adverse Event | 1 | 1 | 0 |
| Blinded Treatment Period | Physician Decision | 0 | 1 | 0 |
| Blinded Treatment Period | Study terminated by sponsor | 8 | 4 | 0 |
| Open Label Period | Physician Decision | 0 | 0 | 1 |
| Open Label Period | Study terminated by sponsor | 0 | 0 | 21 |
Baseline characteristics
| Characteristic | Period 1: MNK-1411 | Period 1: Placebo | Total |
|---|---|---|---|
| Age, Customized Children (2-11 Years) | 29 Participants | 15 Participants | 44 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment Bulgaria | 0 participants | 0 participants | 2 participants |
| Region of Enrollment Israel | 0 participants | 0 participants | 1 participants |
| Region of Enrollment Italy | 0 participants | 0 participants | 2 participants |
| Region of Enrollment Mexico | 0 participants | 0 participants | 18 participants |
| Region of Enrollment Serbia | 0 participants | 0 participants | 2 participants |
| Region of Enrollment Spain | 0 participants | 0 participants | 6 participants |
| Region of Enrollment Turkey | 0 participants | 0 participants | 3 participants |
| Region of Enrollment United States | 0 participants | 0 participants | 10 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 29 Participants | 15 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 15 | 0 / 24 |
| other Total, other adverse events | 22 / 29 | 15 / 15 | 11 / 24 |
| serious Total, serious adverse events | 0 / 29 | 1 / 15 | 2 / 24 |
Outcome results
Primary
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
Population: Summary aggregate results for all participants enrolled into Period 1 and with a score at Week 24
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Period 1: MNK-1411 | Time to Complete 10 Meter Walk/Run[ | at Baseline | 5.9 seconds |
| Period 1: MNK-1411 | Time to Complete 10 Meter Walk/Run[ | at Week 24 | 5.4 seconds |
| Period 1: Placebo | Time to Complete 10 Meter Walk/Run[ | at Baseline | 7.8 seconds |
| Period 1: Placebo | Time to Complete 10 Meter Walk/Run[ | at Week 24 | 8.7 seconds |
Secondary
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
Population: Summary aggregate results for all participants enrolled into Period 1 and with a score at Week 24
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: MNK-1411 | North Star Ambulatory Assessment (NSAA) Score | at Baseline | 17.9 score on a scale | Standard Deviation 6.8 |
| Period 1: MNK-1411 | North Star Ambulatory Assessment (NSAA) Score | at Week 24 | 20.5 score on a scale | Standard Deviation 7.94 |
| Period 1: Placebo | North Star Ambulatory Assessment (NSAA) Score | at Baseline | 17.1 score on a scale | Standard Deviation 6.4 |
| Period 1: Placebo | North Star Ambulatory Assessment (NSAA) Score | at Week 24 | 16.6 score on a scale | Standard Deviation 8.82 |
Secondary
Quantitative Muscle Testing Scores at Baseline
Quantitative muscle testing measured strength-knee flexion and extension measured in Newtons, using a dynamometer
Time frame: Baseline
Population: Summary aggregate results for all participants enrolled into Period 1 with a score at baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: MNK-1411 | Quantitative Muscle Testing Scores at Baseline | Knee flexion | 26.61 Newtons | Standard Deviation 14.17 |
| Period 1: MNK-1411 | Quantitative Muscle Testing Scores at Baseline | Knee extension | 28.99 Newtons | Standard Deviation 16.24 |
| Period 1: Placebo | Quantitative Muscle Testing Scores at Baseline | Knee flexion | 29.87 Newtons | Standard Deviation 14.17 |
| Period 1: Placebo | Quantitative Muscle Testing Scores at Baseline | Knee extension | 26.64 Newtons | Standard Deviation 15.27 |
Secondary
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
Population: Summary aggregate results for all participants enrolled into Period 1 with a score at Week 24
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: MNK-1411 | Quantitative Muscle Testing Scores at Week 24 | Knee flexion | 33.64 Newtons | Standard Deviation 1578 |
| Period 1: MNK-1411 | Quantitative Muscle Testing Scores at Week 24 | Knee extension | 26.61 Newtons | Standard Deviation 14.17 |
| Period 1: Placebo | Quantitative Muscle Testing Scores at Week 24 | Knee flexion | 25.27 Newtons | Standard Deviation 13.35 |
| Period 1: Placebo | Quantitative Muscle Testing Scores at Week 24 | Knee extension | 29.87 Newtons | Standard Deviation 15.13 |
Secondary
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
Population: Summary aggregate results for all participants enrolled into Period 1
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period 1: MNK-1411 | Summary of Adverse Events in the Blinded Treatment Period | Exposed | 29 Participants |
| Period 1: MNK-1411 | Summary of Adverse Events in the Blinded Treatment Period | Affected by serious adverse events | 0 Participants |
| Period 1: MNK-1411 | Summary of Adverse Events in the Blinded Treatment Period | Affected by non-serious adverse events | 22 Participants |
| Period 1: MNK-1411 | Summary of Adverse Events in the Blinded Treatment Period | Died from any cause | 0 Participants |
| Period 1: Placebo | Summary of Adverse Events in the Blinded Treatment Period | Died from any cause | 0 Participants |
| Period 1: Placebo | Summary of Adverse Events in the Blinded Treatment Period | Exposed | 15 Participants |
| Period 1: Placebo | Summary of Adverse Events in the Blinded Treatment Period | Affected by non-serious adverse events | 15 Participants |
| Period 1: Placebo | Summary of Adverse Events in the Blinded Treatment Period | Affected by serious adverse events | 1 Participants |
Secondary
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
Population: Summary aggregate results for all participants enrolled into Period 2
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Period 1: MNK-1411 | Summary of Adverse Events in the Open Label Period | Exposed | 24 Participants |
| Period 1: MNK-1411 | Summary of Adverse Events in the Open Label Period | Affected by serious adverse events | 2 Participants |
| Period 1: MNK-1411 | Summary of Adverse Events in the Open Label Period | Affected by non-serious adverse events | 11 Participants |
| Period 1: MNK-1411 | Summary of Adverse Events in the Open Label Period | Died from any cause | 0 Participants |
Secondary
Time to Climb 4 Standardized Stairs
Time to Climb 4 Standardized Stairs is a motor performance test
Time frame: Baseline, Week 24
Population: Summary aggregate results for all participants enrolled into Period 1 and with a score at Week 24
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: MNK-1411 | Time to Climb 4 Standardized Stairs | at Baseline | 8.52 seconds | Standard Deviation 8.88 |
| Period 1: MNK-1411 | Time to Climb 4 Standardized Stairs | at Week 24 | 4.71 seconds | Standard Deviation 2.45 |
| Period 1: Placebo | Time to Climb 4 Standardized Stairs | at Baseline | 8.47 seconds | Standard Deviation 4.34 |
| Period 1: Placebo | Time to Climb 4 Standardized Stairs | at Week 24 | 15.09 seconds | Standard Deviation 13.84 |
Secondary
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
Population: Summary aggregate results for all participants who enrolled into Period 1 with a score for this measure at the given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Period 1: MNK-1411 | Time to Stand From a Supine Position | at Baseline | 11.14 seconds | Standard Deviation 9.08 |
| Period 1: MNK-1411 | Time to Stand From a Supine Position | at Week 24 | 7.65 seconds | Standard Deviation 4.99 |
| Period 1: Placebo | Time to Stand From a Supine Position | at Baseline | 15.03 seconds | Standard Deviation 12.45 |
| Period 1: Placebo | Time to Stand From a Supine Position | at Week 24 | 24.89 seconds | Standard Deviation 26.48 |