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

Purpose

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	Intervention	Phase
Duchenne Muscular Dystrophy	Drug: NS-065/NCNP-01 Drug: Placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Participant, Care Provider, Investigator, Outcomes Assessor Primary Purpose: Treatment

Resource links provided by NLM:

Genetics Home Reference related topics: Duchenne and Becker muscular dystrophy

MedlinePlus related topics: Muscular Dystrophy

Genetic and Rare Diseases Information Center resources: Muscular Dystrophy Duchenne Muscular Dystrophy Becker Muscular Dystrophy

U.S. FDA Resources

Further study details as provided by NS Pharma, Inc.:

Primary Outcome Measures:

Incidence of Adverse Events as assessed by CTCAE v4.0. [ Time Frame: 24 weeks of treatment phase ]
Dystrophin protein in muscle as measured by mass spectrometry. [ Time Frame: 20-24 weeks of treatment ]
Drug concentration in plasma. [ Time Frame: 20-24 weeks of treatment ]

Secondary Outcome Measures:

Induction of dystrophin messenger ribonucleic acid (mRNA) in muscle as measured by real time polymerase chain reaction (RT-PCR) for mRNA analysis. [ Time Frame: 20-24 weeks of treatment ]
Induction of dystrophin protein in muscle as measured by western blot and immunofluorescence methods for protein analysis. [ Time Frame: 20-24 weeks of treatment ]
Muscle strength as measured by Quantitative Muscle Testing (QMT). [ Time Frame: 20-24 weeks of treatment ]
Change in distance traveled in the Six-Minute Walk Test (6MWT). [ Time Frame: baseline to 20-24 weeks of treatment ]
Change in Time to Climb 4 Stairs (TTCLIMB). [ Time Frame: baseline to 20-24 weeks of treatment ]
Change in Time to Run/Walk 10 meters (TTRW). [ Time Frame: baseline to 20-24 weeks of treatment ]
Change in Time to Stand (TTSTAND) [ Time Frame: baseline to 20-24 weeks of treatment ]
North Star Ambulatory Assessment (NSAA) results. [ Time Frame: baseline to 20-24 weeks of treatment ]


Estimated Enrollment:	16
Study Start Date:	December 2016
Estimated Study Completion Date:	December 2017
Estimated Primary Completion Date:	December 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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.

Eligibility


Ages Eligible for Study:	4 Years to 9 Years (Child)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02740972

Contacts


Contact: Lauren Morgenroth	412-224-2030	trialinfo@nspharma.com
Contact: Sara Misplay		trialinfo@nspharma.com

Locations


United States, California
UC Davis Medical Center	Recruiting
Sacramento, California, United States
Contact: Erica Goude 916-734-0384 emgoude@ucdavis.edu
Principal Investigator: Craig McDonald, MD
United States, Florida
University of Florida Health	Recruiting
Gainesville, Florida, United States
Contact: Gee Kim 352-273-7573 geekim@ufl.edu
Principal Investigator: Barry Byrne, MD
United States, Illinois
Lurie Children's Hospital	Recruiting
Chicago, Illinois, United States
Contact: Theresa Oswald 312-227-3019 toswald@luriechildrens.org
Principal Investigator: Vamshi Rao, MD
United States, Missouri
Washington University	Recruiting
Saint Louis, Missouri, United States
Contact: Pallavi Anand 314-362-2490 anandp@wustl.edu
Principal Investigator: Anne M Connolly, MD
United States, North Carolina
Duke University Medical Center	Recruiting
Durham, North Carolina, United States
Contact: Karen Cornett 919-684-1143 k.cornett@duke.edu
Principal Investigator: Edward C Smith, MD
United States, Virginia
Children's Hospital of Richmond at VCU	Recruiting
Richmond, Virginia, United States
Contact: Kathy O'Hara 804-828-3862 kathryn.ohara@vcuhealth.org
Principal Investigator: Amy Harper, MD
Canada, Alberta
Alberta Children's Hospital	Not yet recruiting
Calgary, Alberta, Canada
Contact: Tiffany Haig 403-955-3192 tiffany.haig@ahs.ca
Principal Investigator: Jean Mah, MD

Sponsors and Collaborators

NS Pharma, Inc.

Nippon Shinyaku Co Ltd

Cooperative International Neuromuscular Research Group (CINRG)

Therapeutic Research in Neuromuscular Disorders Solutions (TRiNDS)

Investigators


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

More Information


Responsible Party:	NS Pharma, Inc.
ClinicalTrials.gov Identifier:	NCT02740972 History of Changes
Other Study ID Numbers:	NS-065/NCNP-01-201
Study First Received:	March 23, 2016
Last Updated:	April 24, 2017

Additional relevant MeSH terms:


Muscular Dystrophies Muscular Dystrophy, Duchenne Muscular Disorders, Atrophic Muscular Diseases Musculoskeletal Diseases	Neuromuscular Diseases Nervous System Diseases Genetic Diseases, Inborn Genetic Diseases, X-Linked

ClinicalTrials.gov processed this record on July 17, 2017