|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Duchenne Muscular Distrophy
|Medical condition in easily understood language
|Diseases [C] - Nervous System Diseases [C10]
|E.1.2 Medical condition or disease under investigation
|Duchenne muscular dystrophy
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|To determine the effect of MNK-1411 on motor function in subjects with DMD.
|Secondary objectives of the trial
|1-To assess the effect of MNK-1411 on motor skills and strength.
2-To determine the safety and tolerability of MNK-1411 in subjects with DMD.
|Trial contains a sub-study
|Principal inclusion criteria
|Subjects must meet all of the following criteria for inclusion in the study at the Screening Visit and at the Baseline Visit (except as noted):
1. Each subject’s parent or legal guardian must be adequately informed and understand the nature and risks of the study and must be able to provide a signature and date on the ICF. In addition, each subject who is capable of understanding it must sign an assent form. The
consent and assent (where applicable) for this study must be signed before any protocol required procedures are performed.
2. Subjects must be male and between 4 and 8 years of age (inclusive) at the Screening Visit.
3. Subjects must have a documented diagnosis of 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.
4. Subjects taking approved treatments for DMD (by a Health Authority) that target dystrophin gene mutations (eg, 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
5. Subjects should have serum potassium within the reference range at screening. Subjects who have potassium levels below the lower limit of normal may be given potassium supplements and then retested within the 28 day screening period.
6. Subjects and/or subjects’ parent or legal guardian must be able to communicate effectively with study personnel.
7. Subjects and subjects’ parent or legal guardian must be able and willing to follow all protocol requirements and study restrictions.
8. Subjects and subjects’ parent or legal guardian must be able and willing to return for all study visits.
|Principal exclusion criteria
|Subjects are ineligible for study participation if they meet any of the following criteria at the Screening Visit and at the Baseline Visit (except as note):
1. Subject is from a vulnerable population (excluding pediatric populations), as defined by the US CFR Title 45, Part 46, Section 46.111(b) and other local and national regulations, including but not limited to, employees (temporary, part-time, full-time, etc) or family members of the research staff conducting the study, or of the sponsor, or of the clinical research organization, or of the IRB/IEC.
2. Subject 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, 3 mg/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.
3. Subject has been treated with immunosuppressants, or mineralocorticoids (including, but not limited to, spironolactone, eplerone, and carrenone) in the 3 months prior to the Screening Visit.
4. Subject has taken any investigation medication within 30 days or 5 half lifes (whichever is longer) prior to the first dose of study drug.
5. Subject is unwilling to receive, or is intolerant of, SC injections.
6. Subject has symptomatic cardiomyopathy in the opinion of the investigator.
7. Subject is unable to complete the 10 meter Walk/Run test at the Screening and/or Baseline Visit.
8. Subject has a history of any drug allergy, hypersensitivity, or intolerance to cosyntropin, H.P. Acthar® Gel or other ACTH products.
9. Subject has a history or evidence of active infection or febrile illness within 7 days prior to the Screening Visit or subject has a clinically significant infection requiring administration of intravenous antibiotics or hospitalization in the 4 weeks prior to the Screening Visit or between the Screening Visit and the first dose of study drug.
10. Subject has any known contraindication(s) to the class of ACTH products including, but not limited to:
Any primary adrenocortical insufficiency or adrenal cortical hyperfunction.
Any current congestive heart failure (defined as New York Heart Association Functional Class III to IV).
Peptic ulcer (within 24 weeks prior to the Screening Visit).
Recent major surgery (within 24 weeks prior to the Screening Visit).
11. Subject has Type 1 or Type 2 diabetes mellitus.
12. Subject has a history of chronic active hepatitis including acute or chronic hepatitis B, or acute or chronic hepatitis C.
13. Subject has a history of tuberculosis (TB) infection, any signs/symptoms of TB, or any close contact with an individual with an active TB infection.
14. Subject 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.
15. Subject has any solid tumor or hematologic malignancy currently diagnosed or undergoing therapy, or has received therapy for any solid tumor or hematological malignancy in the 5 years prior to the Screening Visit; with the exception of treated and cured basal cell
carcinoma or treated and cured squamous cell carcinoma of the skin.
16. Subject has any of the following laboratory abnormalities at the Screening Visit:
Hemoglobin ≤ 8.0 g/dL.
Platelets ≤ 50,000 cells/μL.
Absolute neutrophil count ≤ 1000 cells/μL.
Glycosylated hemoglobin (HbA1c) > 6.5%.
Positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb), or positive Hepatitis C virus antibody (HCV). (If HCV is positive at screening, HCV polymerase chain reaction (PCR) will be automatically analyzed. Subjects with a positive HCV must have HCV PCR < 25 IU/mL at the Screening Visit to be eligible).
Positive or indeterminate interferon gamma release assay (IGRA) for TB.
17. Subject has any other clinically significant disease, disorder or laboratory abnormality which, in the opinion of the investigator (by its nature or by being inadequately controlled), might put the patient at risk due to participation in the study, or may influence the results of the study or the subject’s ability to complete the study.
|E.5 End points
|Primary end point(s)
|Change from baseline in 10 meter walk/run time
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|1-Change from baseline in quantitative muscle testing, the 4 Stair Climb, Time to Stand, and the North Star Ambulatory Assessment (NSAA)
2-Summary of general safety profile, including AEs, vital signs, immunogenicity, and laboratory assessments over the entire study.
|Timepoint(s) of evaluation of this end point
2-Over the entire study
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|Last Follow-up visit:
-Subjects who complete the study and do not enter the open label extension will have their Follow-up Visit at approximately Week 28.
-Subjects who complete the open label extension will have their Follow-up Visit at approximately Week 52.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days