Extension Study of NS-065/NCNP-01 in Boys With Duchenne Muscular Dystrophy (DMD)

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: NS-065/NCNP-01


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 10 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Low Dose cohort of 40 mg/kg and High Dose cohort of 80 mg/kg
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NS-065/NCNP-01 40mg/kg<br>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. | Drug: NS-065/NCNP-01<br>* Received during weekly intravenous infusions<br>|
| Experimental: NS-065/NCNP-01 80mg/kg<br>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. | Drug: NS-065/NCNP-01<br>* Received during weekly intravenous infusions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202 | 
| 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 | Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202 | 
| 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. | Up to 192 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202 | 
| 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). | Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202 | 
| 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) | Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202 | 
| 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). | Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202 | 
| 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. | Baseline 201, Weeks 37, 49, 73, 109, 157 in Study 202 | 
| 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) | Baseline 201, Weeks 37, 49, 73, 109, 157 in Study 202 | 
| 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. | Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202 | 
| 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. | Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202 | 
| 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. | Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202 | 
| 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. | Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202 | 
| 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. | Baseline 201, Weeks 37, 49, 73, 109, 157, 205 in Study 202 |