Clinical Trial in Male Subjects with Muscular Disease

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2017-004139-35-ES
• Date of registration: 19/03/2018
• Prospective Registration: Yes
• Primary sponsor: Mallinckrodt ARD Inc.
• Public title: Clinical Trial in Male Subjects with Muscular Disease
• Scientific title: A Multicenter, Randomized, Parallel Group, Double Blind, Multiple Dose, Placebo Controlled Study to Assess the Efficacy and Safety of MNK-1411 in Male Subjects 4 to 8 Years of Age With Duchenne Muscular Dystrophy
• Date of first enrolment: 12/06/2018
• Target sample size: 132
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004139-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, Bulgaria, Canada, Chile, Germany, Israel, Italy, Netherlands, Serbia, Spain, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trial Lead
• Affiliation: Mallinckrodt ARD Inc.

• Name: Clinical Trial Lead
• Affiliation: Mallinckrodt ARD Inc.

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 132
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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. Transient previous use of corticosteroids will be evaluated on a case-by-case basis by the sponsor or designee. Inhaled corticosteroids will be permitted if given at a stable dose for the 3 months prior to the first dose of study drug and the subject will remain on that dose throughout the study. 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:
Asthma.
Acute psychoses.
Any primary adrenocortical insufficiency or adrenal cortical hyperfunction.
Cushing’s Syndrome.
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.

Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Duchenne Muscular Distrophy
MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Cosyntropin acetate
Product Code: MNK-1411
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: TETRACOSACTIDE HEXAACETATE
CAS Number: 22633-88-1
Other descriptive name: Cosyntropin acetate
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Suspension for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: To determine the effect of MNK-1411 on motor function in subjects with DMD.

Timepoint(s) of evaluation of this end point: Week 24

Secondary Objective: 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.

Primary end point(s): Change from baseline in 10 meter walk/run time

Secondary Outcome(s)

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: 1-Week 24
2-Over the entire study

Secondary ID(s)

MNK14112096

Source(s) of Monetary Support

Mallinckrodt ARD Inc.

Ethics review

Status: Approved
Approval date: 30/05/2018
Contact: