Back to resultsExtension Study of NS-065/NCNP-01 in Boys With Duchenne Muscular Dystrophy (DMD)
Primary Purpose
Duchenne Muscular Dystrophy
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
NS-065/NCNP-01
Sponsored by
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy
Eligibility Criteria
Inclusion Criteria:
- Completed Study NS-065/NCNP-01-201 through Week 25.
- Willing and able to comply with scheduled visits, investigational product administration plan, and study procedures.
- Stable dose of glucocorticoid (GC), and is expected to remain on the stable dose for the duration of the study.
Exclusion Criteria:
- Serious or severe adverse event in Study NS-065/NCNP-01-201 that precludes safe use of NS-065/NCNP-01.
- Patient had a treatment which was made for the purpose of dystrophin or its related protein induction after completion of Study NS-065/NCNP-01-201.
- Patient took any other investigational drugs after completion of Study NS-065/NCNP-01-201.
- Patient was judged by the investigator and/or the Sponsor that it was not appropriate to participate in the extension study for other reasons.
Sites / Locations
- UC Davis
- Lurie Children's Hospital
- Washington University
- Duke University Medical Center
- Children's Hospital of Richmond at VCU
- Alberta Children's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
NS-065/NCNP-01 40mg/kg
NS-065/NCNP-01 80mg/kg
Arm Description
Patients receiving 40mg/kg in the NS-065-NCNP-201 study will continue their current dose for an additional 192 weeks or until enrollment in a separate long-term follow up program of NS-065/NCNP-01, whichever is earlier.
Patients receiving 80mg/kg in the NS-065-NCNP-201 study will continue their current dose for an additional 192 weeks or until enrollment in a separate long-term follow up program of NS-065/NCNP-01, whichever is earlier.
Outcomes
Primary Outcome Measures
Change From Baseline in Time to Stand (TTSTAND) Versus Matched Historical Controls
A primary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Time to Stand (TTSTAND)
Change From Baseline in Time to Stand (TTSTAND) Velocity Versus Matched Historical Controls
A primary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Time to Stand (TTSTAND) Velocity
Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0.
For adverse events (AEs) starting in study 201 (NCT02740972) which are not resolved at the time of enrollment into this study 202, any change in outcome or relatedness were reported in study 201.
For AEs starting in study 201 which increase in severity or becomes serious after enrollment in this study 202, a new AE was reported in this study.
Treatment-emergent AEs (TEAEs) were summarized by dose level. Coding was done by system organ class and preferred term (using the Medical Dictionary for Regulatory Activities (MedDRA)). Level of severity was assessed using the CTCAE grading system.
Secondary Outcome Measures
Change From Baseline in Time to Run/Walk 10 Meters Test (TTRW) Versus Matched Historical Controls
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Time to Run/Walk 10 meters test (TTRW)
Change From Baseline in Time to Run/Walk 10 Meters Test (TTRW) Velocity Versus Matched Historical Controls
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Time to Run/Walk 10 meters test (TTRW) Velocity.
The results were converted into velocity (meter/time).
Change From Baseline in Time to Climb 4 Stairs (TTCLIMB) Versus Matched Historical Controls
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Time to Climb 4 stairs (TTCLIMB)
Change From Baseline in Time to Climb 4 Stairs (TTCLIMB) Velocity Versus Matched Historical Controls
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Time to Climb 4 stairs (TTCLIMB) Velocity. The results were converted into velocity (meter/time).
Change From Baseline in North Star Ambulatory Assessment (NSAA) Score Versus Matched Historical Controls
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): 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.
Change From Baseline in Six-Minute Walk Test (6MWT) Versus Matched Historical Controls
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Six-Minute Walk Test (6MWT)
Change From Baseline in Quantitative Muscle Testing (QMT) for Handgrip Versus Matched Historical Controls
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Quantitative Muscle Testing (QMT) for Handgrip For QMT tests, the higher of each of the bilateral scores recorded for each muscle group at each visit were analyzed. QMT tests were analyzed by dominant/non-dominant side.
QMT is a well-established method for measuring muscle weakness in neuromuscular disease. Patients will be placed on an examination table with a back-support system to eliminate the need for manual back stabilization. Following a single practice administration, each patient will complete a scored QMT evaluation (perform 2 tests; with the higher of the 2 values used for data analysis). QMT will be performed by recording force in pounds through a direct computer interface with a strain gauge.
Change From Baseline in Quantitative Muscle Testing (QMT) for Elbow Flexors Versus Matched Historical Controls
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Quantitative Muscle Testing (QMT) for Elbow Flexors For QMT tests, the higher of each of the bilateral scores recorded for each muscle group at each visit were analyzed. QMT tests were analyzed by dominant/non-dominant side.
QMT is a well-established method for measuring muscle weakness in neuromuscular disease. Patients will be placed on an examination table with a back-support system to eliminate the need for manual back stabilization. Following a single practice administration, each patient will complete a scored QMT evaluation (perform 2 tests; with the higher of the 2 values used for data analysis). QMT will be performed by recording force in pounds through a direct computer interface with a strain gauge.
Change From Baseline in Quantitative Muscle Testing (QMT) for Elbow Extensors Versus Matched Historical Controls
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Quantitative Muscle Testing (QMT) for Elbow Extensors For QMT tests, the higher of each of the bilateral scores recorded for each muscle group at each visit were analyzed. QMT tests were analyzed by dominant/non-dominant side.
QMT is a well-established method for measuring muscle weakness in neuromuscular disease. Patients will be placed on an examination table with a back-support system to eliminate the need for manual back stabilization. Following a single practice administration, each patient will complete a scored QMT evaluation (perform 2 tests; with the higher of the 2 values used for data analysis). QMT will be performed by recording force in pounds through a direct computer interface with a strain gauge.
Change From Baseline in Quantitative Muscle Testing (QMT) for Knee Flexors Versus Matched Historical Controls
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Quantitative Muscle Testing (QMT) for Knee Flexors For QMT tests, the higher of each of the bilateral scores recorded for each muscle group at each visit were analyzed. QMT tests were analyzed by dominant/non-dominant side.
QMT is a well-established method for measuring muscle weakness in neuromuscular disease. Patients will be placed on an examination table with a back-support system to eliminate the need for manual back stabilization. Following a single practice administration, each patient will complete a scored QMT evaluation (perform 2 tests; with the higher of the 2 values used for data analysis). QMT will be performed by recording force in pounds through a direct computer interface with a strain gauge.
Change From Baseline in Quantitative Muscle Testing (QMT) for Knee Extensors Versus Matched Historical Controls
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Quantitative Muscle Testing (QMT) for Knee Extensors For QMT tests, the higher of each of the bilateral scores recorded for each muscle group at each visit were analyzed. QMT tests were analyzed by dominant/non-dominant side.
QMT is a well-established method for measuring muscle weakness in neuromuscular disease. Patients will be placed on an examination table with a back-support system to eliminate the need for manual back stabilization. Following a single practice administration, each patient will complete a scored QMT evaluation (perform 2 tests; with the higher of the 2 values used for data analysis). QMT will be performed by recording force in pounds through a direct computer interface with a strain gauge.
Full Information
NCT ID
NCT03167255
First Posted
May 22, 2017
Last Updated
December 1, 2022
Sponsor
NS Pharma, Inc.
Collaborators
Nippon Shinyaku Co., Ltd., Cooperative International Neuromuscular Research Group, Therapeutic Research in Neuromuscular Disorders Solutions (TRiNDS)
1. Study Identification
Unique Protocol Identification Number
NCT03167255
Brief Title
Extension Study of NS-065/NCNP-01 in Boys With Duchenne Muscular Dystrophy (DMD)
Official Title
A Phase II, Open-Label, Extension Study to Assess the Safety and Efficacy of NS-065/NCNP-01 in Boys With Duchenne Muscular Dystrophy (DMD)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
July 6, 2017 (Actual)
Primary Completion Date
October 20, 2021 (Actual)
Study Completion Date
November 15, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NS Pharma, Inc.
Collaborators
Nippon Shinyaku Co., Ltd., Cooperative International Neuromuscular Research Group, Therapeutic Research in Neuromuscular Disorders Solutions (TRiNDS)
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 an open-label, extension study of NS-065/NCNP-01 administered intravenously once weekly for an additional 192 weeks to boys with DMD who complete Study NS-065/NCNP-01-201.
Detailed Description
This is a Phase II, multicenter, open-label, extension study of NS-065/NCNP-01 administered intravenously once weekly for an additional 192 weeks to boys with DMD who complete Study NS-065/NCNP-01-201. This study will evaluate the safety, tolerability, and clinical efficacy of NS-065/NCNP-01 at dose levels of up to 80 mg/kg/week administered by weekly IV infusion over an additional treatment period of 192 weeks or until enrollment in a separate long-term follow up program of NS-065/NCNP-01, whichever is earlier.
Patients who complete the Phase II Dose-finding Study NS-065/NCNP-01-201 are eligible to enroll.
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
Parallel Assignment
Model Description
Low Dose cohort of 40 mg/kg and High Dose cohort of 80 mg/kg
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NS-065/NCNP-01 40mg/kg
Arm Type
Experimental
Arm Description
Patients receiving 40mg/kg in the NS-065-NCNP-201 study will continue their current dose for an additional 192 weeks or until enrollment in a separate long-term follow up program of NS-065/NCNP-01, whichever is earlier.
Arm Title
NS-065/NCNP-01 80mg/kg
Arm Type
Experimental
Arm Description
Patients receiving 80mg/kg in the NS-065-NCNP-201 study will continue their current dose for an additional 192 weeks or until enrollment in a separate long-term follow up program of NS-065/NCNP-01, whichever is earlier.
Intervention Type
Drug
Intervention Name(s)
NS-065/NCNP-01
Intervention Description
Received during weekly intravenous infusions
Primary Outcome Measure Information:
Title
Change From Baseline in Time to Stand (TTSTAND) Versus Matched Historical Controls
Description
A primary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Time to Stand (TTSTAND)
Time Frame
Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202
Title
Change From Baseline in Time to Stand (TTSTAND) Velocity Versus Matched Historical Controls
Description
A primary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Time to Stand (TTSTAND) Velocity
Time Frame
Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202
Title
Number of Participants With Treatment Related Adverse Events as Assessed by CTCAE v4.0.
Description
For adverse events (AEs) starting in study 201 (NCT02740972) which are not resolved at the time of enrollment into this study 202, any change in outcome or relatedness were reported in study 201.
For AEs starting in study 201 which increase in severity or becomes serious after enrollment in this study 202, a new AE was reported in this study.
Treatment-emergent AEs (TEAEs) were summarized by dose level. Coding was done by system organ class and preferred term (using the Medical Dictionary for Regulatory Activities (MedDRA)). Level of severity was assessed using the CTCAE grading system.
Time Frame
Up to 192 weeks of treatment
Secondary Outcome Measure Information:
Title
Change From Baseline in Time to Run/Walk 10 Meters Test (TTRW) Versus Matched Historical Controls
Description
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Time to Run/Walk 10 meters test (TTRW)
Time Frame
Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202
Title
Change From Baseline in Time to Run/Walk 10 Meters Test (TTRW) Velocity Versus Matched Historical Controls
Description
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Time to Run/Walk 10 meters test (TTRW) Velocity.
The results were converted into velocity (meter/time).
Time Frame
Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202
Title
Change From Baseline in Time to Climb 4 Stairs (TTCLIMB) Versus Matched Historical Controls
Description
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Time to Climb 4 stairs (TTCLIMB)
Time Frame
Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202
Title
Change From Baseline in Time to Climb 4 Stairs (TTCLIMB) Velocity Versus Matched Historical Controls
Description
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Time to Climb 4 stairs (TTCLIMB) Velocity. The results were converted into velocity (meter/time).
Time Frame
Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202
Title
Change From Baseline in North Star Ambulatory Assessment (NSAA) Score Versus Matched Historical Controls
Description
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): 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 Frame
Baseline 201, Weeks 37, 49, 73, 109, 157 in Study 202
Title
Change From Baseline in Six-Minute Walk Test (6MWT) Versus Matched Historical Controls
Description
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Six-Minute Walk Test (6MWT)
Time Frame
Baseline 201, Weeks 37, 49, 73, 109, 157 in Study 202
Title
Change From Baseline in Quantitative Muscle Testing (QMT) for Handgrip Versus Matched Historical Controls
Description
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Quantitative Muscle Testing (QMT) for Handgrip For QMT tests, the higher of each of the bilateral scores recorded for each muscle group at each visit were analyzed. QMT tests were analyzed by dominant/non-dominant side.
QMT is a well-established method for measuring muscle weakness in neuromuscular disease. Patients will be placed on an examination table with a back-support system to eliminate the need for manual back stabilization. Following a single practice administration, each patient will complete a scored QMT evaluation (perform 2 tests; with the higher of the 2 values used for data analysis). QMT will be performed by recording force in pounds through a direct computer interface with a strain gauge.
Time Frame
Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202
Title
Change From Baseline in Quantitative Muscle Testing (QMT) for Elbow Flexors Versus Matched Historical Controls
Description
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Quantitative Muscle Testing (QMT) for Elbow Flexors For QMT tests, the higher of each of the bilateral scores recorded for each muscle group at each visit were analyzed. QMT tests were analyzed by dominant/non-dominant side.
QMT is a well-established method for measuring muscle weakness in neuromuscular disease. Patients will be placed on an examination table with a back-support system to eliminate the need for manual back stabilization. Following a single practice administration, each patient will complete a scored QMT evaluation (perform 2 tests; with the higher of the 2 values used for data analysis). QMT will be performed by recording force in pounds through a direct computer interface with a strain gauge.
Time Frame
Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202
Title
Change From Baseline in Quantitative Muscle Testing (QMT) for Elbow Extensors Versus Matched Historical Controls
Description
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Quantitative Muscle Testing (QMT) for Elbow Extensors For QMT tests, the higher of each of the bilateral scores recorded for each muscle group at each visit were analyzed. QMT tests were analyzed by dominant/non-dominant side.
QMT is a well-established method for measuring muscle weakness in neuromuscular disease. Patients will be placed on an examination table with a back-support system to eliminate the need for manual back stabilization. Following a single practice administration, each patient will complete a scored QMT evaluation (perform 2 tests; with the higher of the 2 values used for data analysis). QMT will be performed by recording force in pounds through a direct computer interface with a strain gauge.
Time Frame
Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202
Title
Change From Baseline in Quantitative Muscle Testing (QMT) for Knee Flexors Versus Matched Historical Controls
Description
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Quantitative Muscle Testing (QMT) for Knee Flexors For QMT tests, the higher of each of the bilateral scores recorded for each muscle group at each visit were analyzed. QMT tests were analyzed by dominant/non-dominant side.
QMT is a well-established method for measuring muscle weakness in neuromuscular disease. Patients will be placed on an examination table with a back-support system to eliminate the need for manual back stabilization. Following a single practice administration, each patient will complete a scored QMT evaluation (perform 2 tests; with the higher of the 2 values used for data analysis). QMT will be performed by recording force in pounds through a direct computer interface with a strain gauge.
Time Frame
Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202
Title
Change From Baseline in Quantitative Muscle Testing (QMT) for Knee Extensors Versus Matched Historical Controls
Description
A secondary efficacy endpoint was compared to Baseline of Study 201 (NCT02740972): Quantitative Muscle Testing (QMT) for Knee Extensors For QMT tests, the higher of each of the bilateral scores recorded for each muscle group at each visit were analyzed. QMT tests were analyzed by dominant/non-dominant side.
QMT is a well-established method for measuring muscle weakness in neuromuscular disease. Patients will be placed on an examination table with a back-support system to eliminate the need for manual back stabilization. Following a single practice administration, each patient will complete a scored QMT evaluation (perform 2 tests; with the higher of the 2 values used for data analysis). QMT will be performed by recording force in pounds through a direct computer interface with a strain gauge.
Time Frame
Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202
10. Eligibility
Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Completed Study NS-065/NCNP-01-201 through Week 25.
Willing and able to comply with scheduled visits, investigational product administration plan, and study procedures.
Stable dose of glucocorticoid (GC), and is expected to remain on the stable dose for the duration of the study.
Exclusion Criteria:
Serious or severe adverse event in Study NS-065/NCNP-01-201 that precludes safe use of NS-065/NCNP-01.
Patient had a treatment which was made for the purpose of dystrophin or its related protein induction after completion of Study NS-065/NCNP-01-201.
Patient took any other investigational drugs after completion of Study NS-065/NCNP-01-201.
Patient was judged by the investigator and/or the Sponsor that it was not appropriate to participate in the extension study for other reasons.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paula R. Clemens, MD
Organizational Affiliation
University of Pittsburgh
Official's Role
Study Chair
Facility Information:
Facility Name
UC Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Lurie Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Children's Hospital of Richmond at VCU
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Alberta Children's Hospital
City
Calgary
State/Province
Alberta
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Extension Study of NS-065/NCNP-01 in Boys With Duchenne Muscular Dystrophy (DMD)
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