Back to resultsNS-089/NCNP-02-201 in Boys With Duchenne Muscular Dystrophy (DMD)
Primary Purpose
Duchenne Muscular Dystrophy
Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
NS-089/NCNP-02
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 44 to restore the dystrophin mRNA reading frame Able to walk independently without assistive devices Ability 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., oxandrolone) or products containing resveratrol or adenosine triphosphate within 3 months prior to first dose of study drug Current or previous treatment with any other investigational drug within 3 months prior to the first dose of study drug or within 5 times the half-life of a medication, whichever is longer Surgery within the 3 months prior to the first dose of study drug or planned during the study duration Previously treated in an interventional study of NS-089/NCNP-02 Having taken any gene therapy or other exon-skipping oligonucleotide Other exclusion criteria may apply.
Sites / Locations
- Shriners Hospital for Children
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
NS-089/NCNP-02
Arm Description
Experimental: NS-089/NCNP-02 NS-089/NCNP-02 solution for infusion (Cohort 1) NS-089/NCNP-02 solution for infusion (Cohort 2)
Outcomes
Primary Outcome Measures
Adverse Event and Adverse Drug Reaction
Plasma pharmacokinetic (PK) parameters
Plasma pharmacokinetic (PK) parameters
Plasma pharmacokinetic (PK) parameters
Plasma pharmacokinetic (PK) parameters
Plasma pharmacokinetic (PK) parameters
Plasma pharmacokinetic (PK) parameters
Plasma pharmacokinetic (PK) parameters
Urine pharmacokinetic parameters
Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot).
Secondary Outcome Measures
Change from baseline in skeletal muscle dystrophin protein by mass spectrometry.
Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining.
Change from baseline in percentage of exon 44-skipped mRNA of skeletal muscle dystrophin
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.
Time to Run/Walk 10 Meters (TTRW)
Time to Stand (TTSTAND)
Total distance of 6 Minute Walk Test (6MWT)
Time to Climb 4 Stairs (TTCLIMB)
Muscle strength measured by Quantitative Muscle Testing (QMT)
Grip and pinch strength
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
1. Study Identification
Unique Protocol Identification Number
NCT05996003
Brief Title
NS-089/NCNP-02-201 in Boys With Duchenne Muscular Dystrophy (DMD)
Official Title
A Phase 2 Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of NS-089/NCNP-02 in Boys With Duchenne Muscular Dystrophy (DMD)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 10, 2023 (Anticipated)
Primary Completion Date
May 28, 2025 (Anticipated)
Study Completion Date
May 28, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NS Pharma, Inc.
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 2, open-label, multi-center, 2-part study of NS-089/NCNP-02 administered by weekly IV infusion to ambulant boys aged ≥4 to <15 years with DMD due to mutations amenable to exon 44 skipping. Participants will receive a selected dose of NS-089/NCNP-02 administered once weekly.
The study consists of 2 parts: Part 1 and Part 2. Six participants (Cohort 1) will participate in both Part 1 and Part 2, and 14 participants (Cohort 2) will be added for Part 2.
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 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
NS-089/NCNP-02
Arm Type
Experimental
Arm Description
Experimental: NS-089/NCNP-02
NS-089/NCNP-02 solution for infusion (Cohort 1)
NS-089/NCNP-02 solution for infusion (Cohort 2)
Intervention Type
Drug
Intervention Name(s)
NS-089/NCNP-02
Other Intervention Name(s)
Brogidirsen
Intervention Description
Cohort 1:
Part 1 Dose Level 1-3: a 4-week Treatment Phase at each treatment dose level
Part 2 Single Dose Level: a 24-week Treatment Phase at the MTD of Part 1
Cohort 2:
Part 2 Single Dose Level: a 24-week Treatment Phase at the MTD of Part 1
Primary Outcome Measure Information:
Title
Adverse Event and Adverse Drug Reaction
Time Frame
through study completion, up to follow-up phone call for Part 2
Title
Plasma pharmacokinetic (PK) parameters
Time Frame
Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Maximum plasma concentration (Cmax) of NS-089/NCNP-02
Title
Plasma pharmacokinetic (PK) parameters
Time Frame
Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Time of the maximum plasma concentration （Tmax） of NS-089/NCNP-02
Title
Plasma pharmacokinetic (PK) parameters
Time Frame
Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Terminal half-life (T1/2) of NS-089/NCNP-02
Title
Plasma pharmacokinetic (PK) parameters
Time Frame
Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Area under the concentration-time curve from time 0 to the last time point (AUC0-t) of NS-089/NCNP-02
Title
Plasma pharmacokinetic (PK) parameters
Time Frame
Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Area under the concentration-time curve from time 0 to infinity (AUC0-∞) of NS-089/NCNP-02
Title
Plasma pharmacokinetic (PK) parameters
Time Frame
[Time Frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Total body clearance (CLtot) of NS-089/NCNP-02
Title
Plasma pharmacokinetic (PK) parameters
Time Frame
Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] The steady-state volume of distribution (Vdss) of NS-089/NCNP-02
Title
Urine pharmacokinetic parameters
Time Frame
Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Urinary excretion of NS-089/NCNP-02
Title
Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot).
Time Frame
Baseline, Week25
Secondary Outcome Measure Information:
Title
Change from baseline in skeletal muscle dystrophin protein by mass spectrometry.
Time Frame
Baseline, Week25
Title
Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining.
Time Frame
Baseline, Week25
Title
Change from baseline in percentage of exon 44-skipped mRNA of skeletal muscle dystrophin
Time Frame
Baseline, Week25
Title
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
Time to Run/Walk 10 Meters (TTRW)
Time Frame
Baseline, Week13, Week25
Title
Time to Stand (TTSTAND)
Time Frame
Baseline, Week13, Week25
Title
Total distance of 6 Minute Walk Test (6MWT)
Time Frame
Baseline, Week13, Week25
Title
Time to Climb 4 Stairs (TTCLIMB)
Time Frame
Baseline, Week13, Week25
Title
Muscle strength measured by Quantitative Muscle Testing (QMT)
Time Frame
Baseline, Week13, Week25
Title
Grip and pinch strength
Time Frame
Baseline, Week13, Week25
Title
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 44 to restore the dystrophin mRNA reading frame
Able to walk independently without assistive devices
Ability 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., oxandrolone) or products containing resveratrol or adenosine triphosphate within 3 months prior to first dose of study drug
Current or previous treatment with any other investigational drug within 3 months prior to the first dose of study drug or within 5 times the half-life of a medication, whichever is longer
Surgery within the 3 months prior to the first dose of study drug or planned during the study duration
Previously treated in an interventional study of NS-089/NCNP-02
Having taken any gene therapy or other exon-skipping oligonucleotide
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
Facility Information:
Facility Name
Shriners Hospital for Children
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
12. IPD Sharing Statement
Learn more about this trial
NS-089/NCNP-02-201 in Boys With Duchenne Muscular Dystrophy (DMD)
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