Back to resultsA Phase 1/2 of NS-050/NCNP-03 in Boys With DMD (Meteor50)
Primary Purpose
Duchenne Muscular Dystrophy
Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
NS-050/NCNP-03
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy
Eligibility Criteria
Inclusion Criteria: Male ≥ 4 years and <15 years of age; Confirmed DMD mutation(s) in the dystrophin gene that is amenable to skipping of exon 50 to restore the dystrophin mRNA reading frame; Able to walk independently without assistive devices; Able to complete the TTSTAND without assistance in <7 seconds; Stable dose of glucocorticoid for at least 3 months and the dose is expected to remain on a stable dose for the duration of the study. Other inclusion criteria may apply. Exclusion Criteria: Evidence of symptomatic cardiomyopathy; Current or previous treatment with anabolic steroids (e.g., oxendolone, oxandrolone) or products containing resveratrol or adenosine triphosphate within 3 months prior to first dose of study drug; Currently taking another investigational drug or has taken another investigational drug within 3 months prior to the first dose of study drug; Surgery within the 3 months prior to the first dose of study drug or planned during the study duration; Having taken any gene therapy. Other exclusion criteria may apply.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
Part 1: NS-050/NCNP-03
Part 1: Placebo
Part 2: NS-050/NCNP-03
Arm Description
Participants will be randomized and receive NS-050/NCNP-03 intravenous (IV) infusions once weekly for 2 weeks at each of MAD levels (1.95, 5, 10, 20, 40, and 80 mg/kg).
Participants will be randomized and receive NS-050/NCNP-03 placebo-matching IV infusions once weekly for 2 weeks at each of MAD levels.
Participants will receive NS-050/NCNP-03 IV infusions once weekly for 24 weeks at the dosage selected by the Data and Safety Monitoring Board (DSMB) at the conclusion of Part 1.
Outcomes
Primary Outcome Measures
Part 1: Overall Summary of Treatment-emergent Adverse Events (TEAEs)
TEAEs will be summarized both at the patient level for number of TEAEs, highest severity, relationship, action, and outcome, and at the TEAE level (summarizing events) by system organ class (SOC) and preferred term (PT) as well as severity, relationship, action, and outcome.
The most recent version of the Medical Dictionary for Regulatory Activities (MedDRA) will be used for coding TEAEs.
Part 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of NS-050/NCNP-03
Blood samples will be collected at the designated time frame. Pharmacokinetic (PK) parameters of NS-050/NCNP-03 will be calculated using non-compartmental methods.
Part 1: Amount of Drug Excreted in Urine of NS-050/NCNP-03
Urine samples will be collected at the designated time frame. PK parameters of NS-050/NCNP-03 will be calculated using non-compartmental methods.
Part 2: Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot)
Secondary Outcome Measures
Part 2: Change from baseline in skeletal muscle dystrophin protein by mass spectrometry
Part 2: Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining
Part 2: Change from baseline in percentage of exon 50-skipped mRNA of skeletal muscle dystrophin
Part 2: North Star Ambulatory Assessment (NSAA) score
The NSAA is a functional scale devised for use in ambulant children with Duchenne muscular dystrophy (DMD). It consists of 17 activities graded 0 (unable to perform), 1 (performs with modifications), 2 (normal movement). It assesses abilities necessary to remain ambulant that have been found to progressively deteriorate in untreated DMD patients, as well as in other muscular dystrophies such as Becker Muscular Dystrophy. NSAA Total Score ranges from 0 to 34, with a score of 34 implying normal function.
Part 2: Time to Stand (TTSTAND)
Part 2: Time to Run/Walk 10 Meters (TTRW)
Part 2: Time to Climb 4 Stairs (TTCLIMB)
Part 2: Total distance of 6 Minute Walk Test (6MWT)
Part 2: Muscle strength measured by Quantitative Muscle Testing (QMT)
Part 2: Grip and Pinch strength
Part 2: Performance of Upper Limb (PUL) 2.0. score
The PUL 2.0 provides both a total score and sub-scores for the 3 domains (shoulder, middle, and distal) that in DMD are progressively involved with a proximal to distal gradient. The PUL includes 22 items with an entry item to define the starting functional level. The 22 items are subdivided into the high level shoulder dimension (6 items), middle level elbow dimension (9 items), and distal wrist and hand dimension (7 items). For weaker patients, a low score on the entry item (0 2) means high level items do not need to be performed. Scoring options vary across the scale between 0-1 and 0-2 according to performance. Each dimension can be scored separately with a maximum score of 12 for the high level shoulder dimension, 17 for the middle level elbow dimension, and 13 for the distal wrist and hand dimension. A total score can be achieved by adding the 3 level scores (maximum total score of 42).
Full Information
NCT ID
NCT06053814
First Posted
September 19, 2023
Last Updated
September 19, 2023
Sponsor
NS Pharma, Inc.
Collaborators
Nippon Shinyaku Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT06053814
Brief Title
A Phase 1/2 of NS-050/NCNP-03 in Boys With DMD (Meteor50)
Official Title
A Phase 1/2, First in Human, Multiple-dose, 2-part Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NS-050/NCNP-03 in Boys With Duchenne Muscular Dystrophy (DMD)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
June 2026 (Anticipated)
Study Completion Date
July 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NS Pharma, Inc.
Collaborators
Nippon Shinyaku Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 1/2 study of Multiple-Ascending Dose (MAD) levels for 12 weeks of treatment followed by 24 weeks of open-label treatment with a selected dose of NS-050/NCNP-03 administered once weekly to ambulant boys with DMD, who have a DMD mutation amenable to exon 50 skipping.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part 1: NS-050/NCNP-03
Arm Type
Experimental
Arm Description
Participants will be randomized and receive NS-050/NCNP-03 intravenous (IV) infusions once weekly for 2 weeks at each of MAD levels (1.95, 5, 10, 20, 40, and 80 mg/kg).
Arm Title
Part 1: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will be randomized and receive NS-050/NCNP-03 placebo-matching IV infusions once weekly for 2 weeks at each of MAD levels.
Arm Title
Part 2: NS-050/NCNP-03
Arm Type
Experimental
Arm Description
Participants will receive NS-050/NCNP-03 IV infusions once weekly for 24 weeks at the dosage selected by the Data and Safety Monitoring Board (DSMB) at the conclusion of Part 1.
Intervention Type
Drug
Intervention Name(s)
NS-050/NCNP-03
Intervention Description
NS-050/NCNP-03 solution for IV infusion.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
NS-050/NCNP-03 placebo-matching solution for IV infusion.
Primary Outcome Measure Information:
Title
Part 1: Overall Summary of Treatment-emergent Adverse Events (TEAEs)
Description
TEAEs will be summarized both at the patient level for number of TEAEs, highest severity, relationship, action, and outcome, and at the TEAE level (summarizing events) by system organ class (SOC) and preferred term (PT) as well as severity, relationship, action, and outcome.
The most recent version of the Medical Dictionary for Regulatory Activities (MedDRA) will be used for coding TEAEs.
Time Frame
Baseline up to Week 24
Title
Part 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of NS-050/NCNP-03
Description
Blood samples will be collected at the designated time frame. Pharmacokinetic (PK) parameters of NS-050/NCNP-03 will be calculated using non-compartmental methods.
Time Frame
Day 1 (1st dose) for each dose level
Title
Part 1: Amount of Drug Excreted in Urine of NS-050/NCNP-03
Description
Urine samples will be collected at the designated time frame. PK parameters of NS-050/NCNP-03 will be calculated using non-compartmental methods.
Time Frame
Day 1 (1st dose) for each dose level
Title
Part 2: Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot)
Time Frame
Baseline, Week25
Secondary Outcome Measure Information:
Title
Part 2: Change from baseline in skeletal muscle dystrophin protein by mass spectrometry
Time Frame
Baseline, Week25
Title
Part 2: Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining
Time Frame
Baseline, Week25
Title
Part 2: Change from baseline in percentage of exon 50-skipped mRNA of skeletal muscle dystrophin
Time Frame
Baseline, Week25
Title
Part 2: North Star Ambulatory Assessment (NSAA) score
Description
The NSAA is a functional scale devised for use in ambulant children with Duchenne muscular dystrophy (DMD). It consists of 17 activities graded 0 (unable to perform), 1 (performs with modifications), 2 (normal movement). It assesses abilities necessary to remain ambulant that have been found to progressively deteriorate in untreated DMD patients, as well as in other muscular dystrophies such as Becker Muscular Dystrophy. NSAA Total Score ranges from 0 to 34, with a score of 34 implying normal function.
Time Frame
Baseline, Week13, Week25
Title
Part 2: Time to Stand (TTSTAND)
Time Frame
Baseline, Week13, Week25
Title
Part 2: Time to Run/Walk 10 Meters (TTRW)
Time Frame
Baseline, Week13, Week25
Title
Part 2: Time to Climb 4 Stairs (TTCLIMB)
Time Frame
Baseline, Week13, Week25
Title
Part 2: Total distance of 6 Minute Walk Test (6MWT)
Time Frame
Baseline, Week13, Week25
Title
Part 2: Muscle strength measured by Quantitative Muscle Testing (QMT)
Time Frame
Baseline, Week13, Week25
Title
Part 2: Grip and Pinch strength
Time Frame
Baseline, Week13, Week25
Title
Part 2: Performance of Upper Limb (PUL) 2.0. score
Description
The PUL 2.0 provides both a total score and sub-scores for the 3 domains (shoulder, middle, and distal) that in DMD are progressively involved with a proximal to distal gradient. The PUL includes 22 items with an entry item to define the starting functional level. The 22 items are subdivided into the high level shoulder dimension (6 items), middle level elbow dimension (9 items), and distal wrist and hand dimension (7 items). For weaker patients, a low score on the entry item (0 2) means high level items do not need to be performed. Scoring options vary across the scale between 0-1 and 0-2 according to performance. Each dimension can be scored separately with a maximum score of 12 for the high level shoulder dimension, 17 for the middle level elbow dimension, and 13 for the distal wrist and hand dimension. A total score can be achieved by adding the 3 level scores (maximum total score of 42).
Time Frame
Baseline, Week13, Week25
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male ≥ 4 years and <15 years of age;
Confirmed DMD mutation(s) in the dystrophin gene that is amenable to skipping of exon 50 to restore the dystrophin mRNA reading frame;
Able to walk independently without assistive devices;
Able to complete the TTSTAND without assistance in <7 seconds;
Stable dose of glucocorticoid for at least 3 months and the dose is expected to remain on a stable dose for the duration of the study.
Other inclusion criteria may apply.
Exclusion Criteria:
Evidence of symptomatic cardiomyopathy;
Current or previous treatment with anabolic steroids (e.g., oxendolone, oxandrolone) or products containing resveratrol or adenosine triphosphate within 3 months prior to first dose of study drug;
Currently taking another investigational drug or has taken another investigational drug within 3 months prior to the first dose of study drug;
Surgery within the 3 months prior to the first dose of study drug or planned during the study duration;
Having taken any gene therapy.
Other exclusion criteria may apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Info
Phone
1-866-677-4276
Email
trialinfo@nspharma.com
12. IPD Sharing Statement
Learn more about this trial
A Phase 1/2 of NS-050/NCNP-03 in Boys With DMD (Meteor50)
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