Safety and Dose Finding Study of NS-065/NCNP-01 in Boys With Duchenne Muscular Dystrophy (DMD)

• Sponsor: NS Pharma, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02740972
• Collaborator: Nippon Shinyaku Co., Ltd. (Industry), Cooperative International Neuromuscular Research Group (Other), Therapeutic Research in Neuromuscular Disorders Solutions (Other)
• Enrollment: 16
• Locations: 7
• Arms: 3
• Actual Duration (Months): 16
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main objective of this study is to evaluate the safety of a high (80mg/kg) and low (40mg/kg) dose of NS-065/NCNP-01 delivered as an intravenous infusion in patients with Duchenne Muscular Dystrophy (DMD) amendable to exon 53 skipping. Additional objectives include tolerability, muscle function and strength, pharmacokinetics and pharmacodynamics.

Condition or Disease	Intervention/Treatment	Phase
Duchenne Muscular Dystrophy	Drug: NS-065/NCNP-01; Drug: Placebo	Phase 2

Detailed Description

This is a Phase II, multiple center, 2-period, randomized, placebo-controlled, dose finding study of NS-065/NCNP-01 administered by infusion once weekly for 24 weeks to ambulant boys ages 4-<10 years with DMD. Two dose level cohorts will be enrolled. Period 1 of this study will be conducted in a double-blind fashion. Randomized patients will receive weekly IV infusions of NS-065/NCNP-01 or placebo for the first 4 weeks of their participation (Period

1. and NS-065/NCNP-01 by IV infusion for weeks 5-24 (20 weeks of active treatment - Period 2). Analysis of safety data from Period 1 of the 40mg/kg dose cohort will be completed prior to enrolling patients in the 80mg/kg dose cohort.

Patients completing the 24-week study will be eligible for an open-label extension study.

Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests such as the six-minute walk test (6MWT), time to stand (TTSTAND), time to run/walk 10 meters (TTRW), time to climb 4 stairs (TTCLIMB) and quantitative muscle testing (QMT). All patients will undergo a muscle biopsy of the bicep at baseline and a second muscle biopsy at Week 24.

Safety will be assessed through the collection of adverse events (AEs), blood and urine laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations throughout the study.

Serial blood samples will be taken at four of the study visits to assess the pharmacokinetics of the study drug.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase II, Dose Finding Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NS-065/NCNP-01 in Boys With Duchenne Muscular Dystrophy (DMD)
• Actual Study Start Date: Dec 1, 2016
• Actual Primary Completion Date: Mar 1, 2018
• Actual Study Completion Date: Apr 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NS-065/NCNP-01 40mg/kg Six patients with confirmed DMD with genetic deletions amenable to exon 53 skipping will be administered an intravenous infusion of NS-065/NCNP-01 40mg/kg dose once a week for 24 weeks	Drug: NS-065/NCNP-01
Experimental: NS-065/NCNP-01 80mg/kg Six patients with confirmed DMD with genetic deletions amenable to exon 53 skipping will be administered an intravenous infusion of NS-065/NCNP-01 80mg/kg once a week for 24 weeks	Drug: NS-065/NCNP-01
Placebo Comparator: Placebo Two patients in each of the dose groups will be administered placebo as an intravenous infusion once a week for 4 weeks followed by 20 weeks of open label treatment	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. Incidence of Adverse Events as Assessed by CTCAE v4.0. [24 weeks of treatment]

   Treatment emergent adverse events (TEAEs) were summarized for Period 1 by comparing low dose to high dose to placebo and for Period 2 between the low dose cohort and the high dose cohort. TEAEs were summarized both at the patient level for number of TEAEs, highest severity, relationship, action and outcome and at the TEAE level (summarizing events) by organ system and preferred term TEAE as well as severity, relationship, action and outcome. The Medical Dictionary for Regulatory Activities (MedDRA) version 20.1 was used and the Common Terminology Criteria for Adverse Events (CTCAE) grading.

2. Dystrophin Production by Western Blot [Baseline and 24 weeks of treatment]

   Percentage normal dystrophin production in muscle biopsies from study participants at baseline and after 24 weeks treatment was measured by Western blot. To analyze dystrophin induction, biopsies were taken from a biceps muscle at baseline and the other biceps muscle after 24 weeks of treatment. Muscle samples were snap frozen and delivered to a central laboratory. All laboratory researchers remained blinded to sample identity. Dystrophin protein levels were assessed using standard curves on each gel (range from 0-25% of normal levels) generated by mixing 5 normal control samples with one DMD sample.

Secondary Outcome Measures

1. Dystrophin Production by RT-PCR for mRNA - Percentage of Exons Skipped - Molarity [Baseline and 24 weeks of treatment]

   The alteration of mRNA splicing was measured by RT-PCR of dystrophin mRNA transcripts from a patient muscle biopsy at baseline and after 24 weeks treatment. To analyze dystrophin induction, biopsies were taken from a biceps muscle at baseline and the other biceps muscle after 24 weeks of treatment. Muscle samples were snap frozen and delivered to a central laboratory. All laboratory researchers remained blinded to sample identity. For RT-PCR, bands corresponding to specific versions of the spliced dystrophin mRNA were visualized by gel electrophoresis, and the amounts of different mRNA isoforms were compared.

2. Dystrophin Production by Mass Spectrometry [Baseline and 24 weeks of treatment]

   The production of dystrophin protein was measured by stable isotope mass spectrometry methods from a patient muscle biopsy at baseline and after 24 weeks treatment. To analyze dystrophin induction, biopsies were taken from a biceps muscle at baseline and the other biceps muscle after 24 weeks of treatment. Muscle samples were snap frozen and delivered to a central laboratory. All laboratory researchers remained blinded to sample identity. Dystrophin peptides were identified and quantified using reversed-phase nanoflow high-performance liquid chromatography with high resolution Mass Spectrometry.

3. Dystrophin Production by Immunofluorescence [Baseline and 24 weeks of treatment]

   The production of dystrophin protein was measured by immunofluorescence staining methods from a patient muscle biopsy at baseline and after 24 weeks treatment. To analyze dystrophin induction, biopsies were taken from a biceps muscle at baseline and the other biceps muscle after 24 weeks of treatment. Muscle samples were snap frozen and delivered to a central laboratory. All laboratory researchers remained blinded to sample identity. Immunofluorescence staining for dystrophin was performed on serial muscle biopsy sections in duplicate.

4. Change From Baseline in Muscle Strength as Measured by Quantitative Muscle Testing (QMT). [Baseline and 24 weeks of treatment]

   A secondary efficacy endpoint was compared to Pre-Infusion Visit: quantitative muscle testing (QMT).

5. Change From Baseline in Distance Traveled in the Six-Minute Walk Test (6MWT). [Baseline and 24 weeks of treatment]

   A secondary efficacy endpoint was compared to Pre-Infusion Visit: Six-Minute Walk Test (6MWT).

6. Change From Baseline in Time to Climb 4 Stairs (TTCLIMB). [Baseline and 24 weeks of treatment]

   A secondary efficacy endpoint was compared to Pre-Infusion Visit: Time to Climb 4 Stairs (TTCLIMB).

7. Change From Baseline in Time to Climb 4 Stairs (TTCLIMB) Velocity [Baseline and 24 weeks of treatment]

   A secondary efficacy endpoint was compared to Pre-Infusion Visit: Time to Run/Walk 10 meters (TTRW). The results were converted into velocity (meter/time).

8. Change From Baseline in Time to Run/Walk 10 Meters (TTRW). [Baseline and 24 weeks of treatment]

   A secondary efficacy endpoint was compared to Pre-Infusion Visit: Time to Run/Walk 10 meters (TTRW).

9. Change From Baseline in Time to Run/Walk 10 Meters (TTRW) Velocity. [Baseline and 24 weeks of treatment]

   A secondary efficacy endpoint was compared to Pre-Infusion Visit: Time to Run/Walk 10 meters (TTRW). The results were converted into velocity (meter/time).

10. Change From Baseline in Time to Stand (TTSTAND) [Baseline and 24 weeks of treatment]

    A secondary efficacy endpoint was compared to Pre-Infusion Visit: Time to Stand (TTSTAND)

11. Change From Baseline in Time to Stand (TTSTAND) Velocity [Baseline and 24 weeks of treatment]

    A secondary efficacy endpoint was compared to Pre-Infusion Visit: Time to Stand (TTSTAND).The results were converted into velocity (rise/time).

12. Change From Baseline in North Star Ambulatory Assessment (NSAA) Score. [Baseline and 24 weeks of treatment]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 9 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male ≥ 4 years and <10 years of age

• Confirmed DMD mutation(s) in the dystrophin gene that is amenable to skipping of exon 53 to restore the dystrophin mRNA reading frame;

• Able to walk independently without assistive devices;

• Ability to complete the time to stand, time to run/walk and time to climb assessments;

• Stable dose of glucocorticoid for at least 3 months

Exclusion Criteria:

• Acute illness within 4 weeks prior to the first dose of study medication;

• Evidence of symptomatic cardiomyopathy. [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary];

• Severe allergy or hypersensitivity to medications;

• Severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator;

• Previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator;

• Patient is taking any other investigational drug currently or within 3 months prior to the start of study treatment; or

• Patient has had surgery within the 3 months prior to the first anticipated administration of study medication or surgery is planned for anytime during the duration of the study;

• Patient has previously participated in this study or any other study during which NS-065/NCNP-01 was administered.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC Davis	Sacramento	California	United States	95817
2	University of Florida Health	Gainesville	Florida	United States
3	Lurie Children's Hospital	Chicago	Illinois	United States
4	Washington University	Saint Louis	Missouri	United States
5	Duke University Medical Center	Durham	North Carolina	United States
6	Children's Hospital of Richmond at VCU	Richmond	Virginia	United States
7	Alberta Children's Hospital	Calgary	Alberta	Canada

Sponsors and Collaborators

• NS Pharma, Inc.
• Nippon Shinyaku Co., Ltd.
• Cooperative International Neuromuscular Research Group
• Therapeutic Research in Neuromuscular Disorders Solutions

Investigators

• Study Chair: Paula R. Clemens, MD, University of Pittsburgh

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 28, 2017

More Information

Publications

None provided.

• Responsible Party: NS Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT02740972
• Other Study ID Numbers: NS-065/NCNP-01-201
• First Posted: Apr 15, 2016
• Last Update Posted: Dec 7, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne

Study Results

Participant Flow

Recruitment Details	Study enrollment occurred between December 16, 2016, and August 17, 2017, at 6 sites in the US and Canada.
Pre-assignment Detail	A total of 17 patients were screened at 6 sites in the United States and Canada. Of the 17 patients screened, 1 failed to meet an inclusion criterion.

Arm/Group Title	Placebo (Period 1)	NS-065/NCNP-01 40mg/kg (Period 1)	NS-065/NCNP-01 80mg/kg (Period 1)	NS-065/NCNP-01 40mg/kg (Period 2)	NS-065/NCNP-01 80mg/kg (Period 2)
Arm/Group Description	4-week Double-blinded placebo-controlled period (Period 1) Week 0 - Week 4	4-week Double-blinded placebo-controlled period (Period 1) Week 0 - Week 4	4-week Double-blinded placebo-controlled period (Period 1) Week 0 - Week 4	20-week Open-label treatment period (Period 2) Week 5 - Week 24	20-week Open-label treatment period (Period 2) Week 5 - Week 24
Period Title: 4-week Double-blinded Placebo-controlled
STARTED	5	6	5	0	0
COMPLETED	5	6	5	0	0
NOT COMPLETED	0	0	0	0	0
Period Title: 4-week Double-blinded Placebo-controlled
STARTED	0	0	0	8	8
COMPLETED	0	0	0	8	8
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total
Arm/Group Description	Patients with confirmed DMD with genetic deletions amenable to exon 53 skipping will be administered an intravenous infusion of NS-065/NCNP-01 40mg/kg once a week for 24 weeks	Patients with confirmed DMD with genetic deletions amenable to exon 53 skipping will be administered an intravenous infusion of NS-065/NCNP-01 80mg/kg once a week for 24 weeks	Total of all reporting groups
Overall Participants	8	8	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.5 (1.8)	7.2 (2.0)	7.4 (1.8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	8 100%	8 100%	16 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 12.5%	1 6.3%
Not Hispanic or Latino	8 100%	6 75%	14 87.5%
Unknown or Not Reported	0 0%	1 12.5%	1 6.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 12.5%	1 6.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	8 100%	7 87.5%	15 93.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	23.7 (4.7)	22.3 (6.2)	23.0 (5.3)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	114.6 (6.5)	112.2 (10.0)	113.4 (8.2)
Body Mass Index(BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	17.9 (2.3)	17.4 (2.0)	17.7 (2.1)
Time to run/walk 10m velocity (m/s) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m/s]	1.67 (0.39)	1.88 (0.36)	1.77 (0.37)
Time to run/walk 10m (second) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [second]	6.30 (1.59)	5.55 (1.34)	5.93 (1.47)
Time to stand from supine velocity (rise/s) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [rise/s]	0.26 (0.06)	0.25 (0.09)	0.25 (0.07)
Time to stand from supine (second) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [second]	4.17 (1.15)	4.76 (2.58)	4.44 (1.96)
6-Minute walk test (m) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m]	391.4 (33.3)	353.4 (106.3)	372.4 (78.6)
Time to climb 4 stairs velocity (m/s) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m/s]	0.27 (0.08)	0.32 (0.08)	0.30 (0.08)
Time to climb 4 stairs (second) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [second]	3.90 (0.93)	3.33 (0.94)	3.61 (0.95)
NSAA score (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	24.8 (5.9)	23.8 (5.1)	24.3 (5.4)
Dystrophin Production by Western Blot (% of normal control levels) [Mean (Standard Deviation) ]
Normalized to Myosin	0.3 (0.10)	0.6 (0.82)	0.4 (0.60)
Normalized to Alpha-Actinin	0.2 (0.22)	0.4 (0.67)	0.3 (0.50)
Dystrophin Production by Mass Spectrometry (% of normal control levels) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% of normal control levels]	0.5 (0.15)	0.6 (0.19)	0.6 (0.17)
Dystrophin Production by Immunofluorescence (% of normal control levels) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% of normal control levels]	1.5 (0.98)	1.8 (2.36)	1.7 (1.75)
Dystrophin Production by RT-PCR for mRNA - Percentage of Exons Skipped - Molarity (% of normal control levels) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [% of normal control levels]	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)

Outcome Measures

1. Primary Outcome

Title	Incidence of Adverse Events as Assessed by CTCAE v4.0.
Description	Treatment emergent adverse events (TEAEs) were summarized for Period 1 by comparing low dose to high dose to placebo and for Period 2 between the low dose cohort and the high dose cohort. TEAEs were summarized both at the patient level for number of TEAEs, highest severity, relationship, action and outcome and at the TEAE level (summarizing events) by organ system and preferred term TEAE as well as severity, relationship, action and outcome. The Medical Dictionary for Regulatory Activities (MedDRA) version 20.1 was used and the Common Terminology Criteria for Adverse Events (CTCAE) grading.
Time Frame	24 weeks of treatment

Outcome Measure Data

Analysis Population Description

Within each category, patients were counted only once if they had >1 event reported during the treatment period.

Arm/Group Title	Placebo (Period 1)	NS-065/NCNP-01 40mg/kg (Period 1)	NS-065/NCNP-01 80mg/kg (Period 1)	NS-065/NCNP-01 40mg/kg (Period 2)	NS-065/NCNP-01 80mg/kg (Period 2)	Total
Arm/Group Description	4-week Double-blinded placebo-controlled period (Period 1) Two patients in each of the dose groups will be administered placebo as an intravenous infusion once a week for 4 weeks followed by 20 weeks of open label treatment	4-week Double-blinded placebo-controlled period (Period 1)	4-week Double-blinded placebo-controlled period (Period 1)	20-week Open-label treatment period (Period 2)	20-week Open-label treatment period (Period 2)	Total of all reporting groups
Measure Participants	5	6	5	8	8	16
Participants with TEAE	3 37.5%	4 50%	4 25%	5 NaN	7 NaN	15 NaN
Participants with drug-related TEAE	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Participants with CTCAE ≥ Grade 3	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Participants with TEAEs leading to discontinuation	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Participants with serious TEAE	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN
Death	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN

2. Primary Outcome

Title	Dystrophin Production by Western Blot
Description	Percentage normal dystrophin production in muscle biopsies from study participants at baseline and after 24 weeks treatment was measured by Western blot. To analyze dystrophin induction, biopsies were taken from a biceps muscle at baseline and the other biceps muscle after 24 weeks of treatment. Muscle samples were snap frozen and delivered to a central laboratory. All laboratory researchers remained blinded to sample identity. Dystrophin protein levels were assessed using standard curves on each gel (range from 0-25% of normal levels) generated by mixing 5 normal control samples with one DMD sample.
Time Frame	Baseline and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Normalized to Myosin	5.7 (2.37)	5.9 (4.50)	5.8 (3.47)
Normalized to Alpha-Actinin	5.4 (2.79)	3.7 (2.37)	4.5 (2.64)

3. Secondary Outcome

Title	Dystrophin Production by RT-PCR for mRNA - Percentage of Exons Skipped - Molarity
Description	The alteration of mRNA splicing was measured by RT-PCR of dystrophin mRNA transcripts from a patient muscle biopsy at baseline and after 24 weeks treatment. To analyze dystrophin induction, biopsies were taken from a biceps muscle at baseline and the other biceps muscle after 24 weeks of treatment. Muscle samples were snap frozen and delivered to a central laboratory. All laboratory researchers remained blinded to sample identity. For RT-PCR, bands corresponding to specific versions of the spliced dystrophin mRNA were visualized by gel electrophoresis, and the amounts of different mRNA isoforms were compared.
Time Frame	Baseline and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Mean (Standard Deviation) [% of normal control levels]	17.4 (7.17)	43.9 (16.68)	30.6 (18.45)

4. Secondary Outcome

Title	Dystrophin Production by Mass Spectrometry
Description	The production of dystrophin protein was measured by stable isotope mass spectrometry methods from a patient muscle biopsy at baseline and after 24 weeks treatment. To analyze dystrophin induction, biopsies were taken from a biceps muscle at baseline and the other biceps muscle after 24 weeks of treatment. Muscle samples were snap frozen and delivered to a central laboratory. All laboratory researchers remained blinded to sample identity. Dystrophin peptides were identified and quantified using reversed-phase nanoflow high-performance liquid chromatography with high resolution Mass Spectrometry.
Time Frame	Baseline and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Mean (Standard Deviation) [% of normal control levels]	2.1 (1.09)	4.2 (3.73)	3.1 (2.88)

5. Secondary Outcome

Title	Dystrophin Production by Immunofluorescence
Description	The production of dystrophin protein was measured by immunofluorescence staining methods from a patient muscle biopsy at baseline and after 24 weeks treatment. To analyze dystrophin induction, biopsies were taken from a biceps muscle at baseline and the other biceps muscle after 24 weeks of treatment. Muscle samples were snap frozen and delivered to a central laboratory. All laboratory researchers remained blinded to sample identity. Immunofluorescence staining for dystrophin was performed on serial muscle biopsy sections in duplicate.
Time Frame	Baseline and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Mean (Standard Deviation) [% dystrophin-positive fibers]	14.2 (7.77)	34.8 (20.42)	24.5 (18.32)

6. Secondary Outcome

Title	Change From Baseline in Muscle Strength as Measured by Quantitative Muscle Testing (QMT).
Description	A secondary efficacy endpoint was compared to Pre-Infusion Visit: quantitative muscle testing (QMT).
Time Frame	Baseline and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Handgrip	-0.2029 (2.98334)	-0.8513 (1.85797)	-0.4808 (2.49621)
Dominant Side Handgrip	-0.4173 (2.46596)	-1.0867 (1.75915)	-0.7041 (2.14074)
Non-Dominant Side Handgrip	-0.2280 (3.39211)	-0.1780 (2.27428)	-0.2066 (2.86108)
Elbow Flexors (biceps)	0.3190 (1.99880)	-0.7110 (1.61528)	-0.1224 (1.85326)
Dominant Side Elbow Flexors (biceps)	0.5111 (2.57829)	-0.4468 (1.49138)	0.1006 (2.16263)
Non-Dominant Side Elbow Flexors (biceps)	0.2067 (2.71502)	-0.3732 (2.50228)	-0.0163 (2.54427)
Elbow Extensors (triceps)	0.6777 (2.65006)	0.6895 (1.00990)	0.6828 (2.04299)
Dominant Side Elbow Extensors (triceps)	0.7046 (2.78271)	0.6502 (0.81291)	0.6813 (2.10345)
Non-Dominant Side Elbow Extensors (triceps)	0.0001 (2.34657)	0.5168 (1.44498)	0.2216 (1.95920)
Knee Flexors (hamstrings)	-1.2209 (3.37401)	-0.0283 (3.43240)	-0.7098 (3.32207)
Dominant Side Knee Flexors (hamstrings)	-1.8985 (4.01798)	-0.7175 (3.64572)	-1.3924 (3.76469)
Non-Dominant Side Knee Flexors (hamstrings)	-1.7373 (3.10626)	0.6377 (2.03566)	-0.7194 (2.87696)
Knee Extensors (quadriceps)	-2.2261 (4.82146)	1.5798 (3.33316)	-0.5950 (4.53990)
Dominant Side Knee Extensors (quadriceps)	-2.1524 (4.58595)	2.0867 (2.96796)	-0.3356 (4.41039)
Non-Dominant Side Knee Extensors (quadriceps)	-0.5994 (4.38150)	1.3308 (4.44474)	0.2279 (4.34950)

7. Secondary Outcome

Title	Change From Baseline in Distance Traveled in the Six-Minute Walk Test (6MWT).
Description	A secondary efficacy endpoint was compared to Pre-Infusion Visit: Six-Minute Walk Test (6MWT).
Time Frame	Baseline and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Mean (Standard Deviation) [m]	15.6 (26.40)	44.0 (41.98)	28.9 (36.31)

8. Secondary Outcome

Title	Change From Baseline in Time to Climb 4 Stairs (TTCLIMB).
Description	A secondary efficacy endpoint was compared to Pre-Infusion Visit: Time to Climb 4 Stairs (TTCLIMB).
Time Frame	Baseline and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Mean (Standard Deviation) [second]	-0.34 (1.140)	0.00 (0.600)	-0.17 (0.897)

9. Secondary Outcome

Title	Change From Baseline in Time to Climb 4 Stairs (TTCLIMB) Velocity
Description	A secondary efficacy endpoint was compared to Pre-Infusion Visit: Time to Run/Walk 10 meters (TTRW). The results were converted into velocity (meter/time).
Time Frame	Baseline and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Mean (Standard Deviation) [m/s]	0.07 (0.105)	-0.00 (0.054)	0.32 (0.088)

10. Secondary Outcome

Title	Change From Baseline in Time to Run/Walk 10 Meters (TTRW).
Description	A secondary efficacy endpoint was compared to Pre-Infusion Visit: Time to Run/Walk 10 meters (TTRW).
Time Frame	Baseline and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Mean (Standard Deviation) [second]	-0.65 (1.225)	-0.66 (0.921)	-0.66 (1.047)

11. Secondary Outcome

Title	Change From Baseline in Time to Run/Walk 10 Meters (TTRW) Velocity.
Description	A secondary efficacy endpoint was compared to Pre-Infusion Visit: Time to Run/Walk 10 meters (TTRW). The results were converted into velocity (meter/time).
Time Frame	Baseline and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Mean (Standard Deviation) [m/s]	0.21 (0.291)	0.24 (0.222)	0.23 (0.251)

12. Secondary Outcome

Title	Change From Baseline in Time to Stand (TTSTAND)
Description	A secondary efficacy endpoint was compared to Pre-Infusion Visit: Time to Stand (TTSTAND)
Time Frame	Baseline and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Mean (Standard Deviation) [second]	0.05 (1.446)	-0.44 (0.750)	-0.19 (1.141)

13. Secondary Outcome

Title	Change From Baseline in Time to Stand (TTSTAND) Velocity
Description	A secondary efficacy endpoint was compared to Pre-Infusion Visit: Time to Stand (TTSTAND).The results were converted into velocity (rise/time).
Time Frame	Baseline and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Mean (Standard Deviation) [rise/time]	0.02 (0.093)	0.02 (0.060)	0.02 (0.075)

14. Secondary Outcome

Title	Change From Baseline in 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 and 24 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	NS-065/NCNP-01 40mg/kg	NS-065/NCNP-01 80mg/kg	Total NS-065/NCNP-01 Group
Arm/Group Description	NS-065/NCNP-01 40mg/kg dose once a week for 20-24 weeks	NS-065/NCNP-01 80mg/kg dose once a week for 20-24 weeks	Of the 16 patients randomized, all patients received treatment with NS-065/NCNP-01 and all patients completed treatment with NS-065/NCNP-01.
Measure Participants	8	8	16
Mean (Standard Deviation) [score on a scale]	0.5 (3.07)	1.1 (2.80)	0.8 (2.86)

Adverse Events

Time Frame	24 weeks
Adverse Event Reporting Description	Incidence of Adverse Events as assessed by CTCAE v4.0
Arm/Group Title	Placebo (Period 1)		NS-065/NCNP-01 40mg/kg (Period 1)		NS-065/NCNP-01 80mg/kg (Period 1)		NS-065/NCNP-01 40mg/kg (Period 2)		NS-065/NCNP-01 80mg/kg (Period 2)		Total
Arm/Group Description	4-week Double-blinded placebo-controlled period (Period 1) Week 0 - Week 4 Two patients in each of the dose groups will be administered placebo as an intravenous infusion once a week for 4 weeks followed by 20 weeks of open label treatment		4-week Double-blinded placebo-controlled period (Period 1) Week 0 - Week 4		4-week Double-blinded placebo-controlled period (Period 1) Week 0 - Week 4		20-week Open-label treatment period (Period 2) Week 5 - Week 24		20-week Open-label treatment period (Period 2) Week 5 - Week 24		Total of all reporting groups
All Cause Mortality
	Placebo (Period 1)		NS-065/NCNP-01 40mg/kg (Period 1)		NS-065/NCNP-01 80mg/kg (Period 1)		NS-065/NCNP-01 40mg/kg (Period 2)		NS-065/NCNP-01 80mg/kg (Period 2)		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		0/8 (0%)		0/16 (0%)
Serious Adverse Events
	Placebo (Period 1)		NS-065/NCNP-01 40mg/kg (Period 1)		NS-065/NCNP-01 80mg/kg (Period 1)		NS-065/NCNP-01 40mg/kg (Period 2)		NS-065/NCNP-01 80mg/kg (Period 2)		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		0/8 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Placebo (Period 1)		NS-065/NCNP-01 40mg/kg (Period 1)		NS-065/NCNP-01 80mg/kg (Period 1)		NS-065/NCNP-01 40mg/kg (Period 2)		NS-065/NCNP-01 80mg/kg (Period 2)		Total
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/5 (60%)		4/6 (66.7%)		4/5 (80%)		5/8 (62.5%)		7/8 (87.5%)		15/16 (93.8%)
Ear and labyrinth disorders
Otorrhoea	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/8 (12.5%)		0/8 (0%)		1/16 (6.3%)
Gastrointestinal disorders
Diarrhoea	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/8 (12.5%)		1/8 (12.5%)		2/16 (12.5%)
Vomiting	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		2/8 (25%)		2/16 (12.5%)
General disorders
Facial pain	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)
Infusion site discomfort	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/8 (12.5%)		0/8 (0%)		1/16 (6.3%)
Injection site bruising	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)
Injection site pain	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/8 (0%)		0/8 (0%)		1/16 (6.3%)
Injection site reaction	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)
Pyrexia	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)
Thirst	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)
Immune system disorders
Drug hypersensitivity	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/8 (0%)		0/8 (0%)		1/16 (6.3%)
Infections and infestations
Influenza	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)
Molluscum contagiosum	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)
Nasopharyngitis	1/5 (20%)		0/6 (0%)		1/5 (20%)		0/8 (0%)		4/8 (50%)		4/16 (25%)
Pharyngitis streptococcal	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)
Upper respiratory tract infection	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/8 (12.5%)		0/8 (0%)		1/16 (6.3%)
Injury, poisoning and procedural complications
Arthropod bite	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/8 (12.5%)		0/8 (0%)		1/16 (6.3%)
Arthropod sting	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/8 (12.5%)		0/8 (0%)		1/16 (6.3%)
Contusion	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/8 (0%)		1/8 (12.5%)		2/16 (12.5%)
Fall	1/5 (20%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		0/8 (0%)		1/16 (6.3%)
Joint injury	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/8 (12.5%)		0/8 (0%)		1/16 (6.3%)
Investigations
Blood creatinine increased	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)
Blood potassium increased	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)
Blood urea increased	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/5 (20%)		0/6 (0%)		1/5 (20%)		0/8 (0%)		0/8 (0%)		2/16 (12.5%)
Muscle spasms	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)
Myalgia	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/8 (12.5%)		0/8 (0%)		1/16 (6.3%)
Pain in extremity	0/5 (0%)		0/6 (0%)		0/5 (0%)		1/8 (12.5%)		0/8 (0%)		1/16 (6.3%)
Nervous system disorders
Headache	1/5 (20%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		0/8 (0%)		1/16 (6.3%)
Psychiatric disorders
Abnormal behaviour	1/5 (20%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		0/8 (0%)		1/16 (6.3%)
Anxiety	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/8 (0%)		0/8 (0%)		1/16 (6.3%)
Attention deficit/hyperactivity disorder	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/8 (0%)		0/8 (0%)		1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough	0/5 (0%)		0/6 (0%)		1/5 (20%)		2/8 (25%)		2/8 (25%)		5/16 (31.3%)
Nasal congestion	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		1/8 (12.5%)		0/8 (0%)		2/16 (12.5%)
Respiratory tract congestion	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/8 (0%)		0/8 (0%)		1/16 (6.3%)
Skin and subcutaneous tissue disorders
Dermatitis contact	0/5 (0%)		0/6 (0%)		1/5 (20%)		0/8 (0%)		0/8 (0%)		1/16 (6.3%)
Rash	0/5 (0%)		1/6 (16.7%)		0/5 (0%)		0/8 (0%)		0/8 (0%)		1/16 (6.3%)
Vascular disorders
Peripheral artery occlusion	0/5 (0%)		0/6 (0%)		0/5 (0%)		0/8 (0%)		1/8 (12.5%)		1/16 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The most restrictive relevant agreement on the PI provides that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is not less than 30 days from the time submitted to the sponsor for review.