Study to Assess the Safety, Tolerability, and Efficacy of Viltolarsen in Ambulant and Non-Ambulant Boys With DMD (Galactic53)

• ClinicalTrials.gov Identifier: NCT04956289
• Recruitment Status: Completed
• First Posted: July 9, 2021
• Last Update Posted: July 19, 2023
• Sponsor: NS Pharma, Inc.
• Collaborator: Nippon Shinyaku Co., Ltd.
• Information provided by (Responsible Party): NS Pharma, Inc.

Study Description

Brief Summary:

This is a phase II, open-label study where weekly doses of 80 mg/kg viltolarsen is administered intravenously over a 48-week treatment period to ambulant and non-ambulant DMD patients over the age of 8 years.

Condition or disease	Intervention/treatment	Phase
Duchenne Muscular Dystrophy	Drug: Viltolarsen	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Open-label Study to Assess the Safety, Tolerability, and Efficacy of Viltolarsen in Ambulant and Non-Ambulant Boys With Duchenne Muscular Dystrophy (DMD) Compared to Natural History Controls
• Actual Study Start Date: July 1, 2021
• Actual Primary Completion Date: June 20, 2023
• Actual Study Completion Date: July 13, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Viltolarsen; Patients amenable to exon 53 skipping will receive viltolarsen intravenous (IV) infusions, weekly, at 80 mg/kg for up to 48 weeks.	Drug: Viltolarsen; Received during weekly intravenous infusions; Other Name: NS-065/NCNP-01

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment related Adverse Events as assessed by CTCAE v4.03 [ Time Frame: baseline to up to 48 weeks of treatment ]

Secondary Outcome Measures :

1. Peak Expiratory Flow (PEF) [ Time Frame: baseline to 48 weeks of treatment ]
2. Forced Vital Capacity (FVC) [ Time Frame: baseline to 48 weeks of treatment ]
3. Forced expiratory volume in 1 second (FEV1) [ Time Frame: baseline to 48 weeks of treatment ]
4. Performance of Upper Limb (PUL) [ Time Frame: baseline to 48 weeks of treatment ]
   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).
5. Brooke scale [ Time Frame: baseline to 48 weeks of treatment ]
   The Brooke scale for upper limb has grades ranging from 1 to 6. Grade 1 is given to the patient who can keep both his arms by his sides in the starting position and is then able to abduct the arms fully so that both the arms are touching over the head. Grade 6 is given when the patient is unable to raise his hands to his mouth, and the hands show no functional usefulness.
6. Vignos scale [ Time Frame: baseline to 48 weeks of treatment ]
   The Vignos scale for lower limb has grades ranging from 1 to 10; 1 means that the patient is able to walk and climb stairs without assistance, while 10 means that the patient is bed bound. Ambulant patients score 1 to 6 and non-ambulant patients score 7 to 10 on the Vignos scale.
7. Muscle Strength Measured by Hand-Held Dynamometer [ Time Frame: baseline to 48 weeks of treatment ]
8. North Star Ambulatory Assessment (NSAA) [ Time Frame: baseline to 48 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

• Ages Eligible for Study: 8 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient (if age 18 years or older) or patient's parent(s) or legal guardian(s) has (have) provided written informed consent and Health Insurance Portability and Accountability Act authorization, where applicable, prior to any study-related procedures; patients younger than age 18 years will be asked to give written or verbal assent according to local requirements;

2. Patient has a confirmed diagnosis of DMD defined as:

   1. Patient is male with clinical signs compatible with DMD; and
   2. Patient has a confirmed DMD mutation(s) in the dystrophin gene that is amenable to skipping of exon 53 to restore the dystrophin messenger ribonucleic acid reading frame including determination of unambiguously defined exon boundaries (using techniques such as multiplex ligation-dependent probe amplification, comparative genomic hybridization array, or other techniques with similar capability);
3. Patient is more than 8 years of age at time of first infusion in the study;
4. Patient has a Brooke scale rating of 3 or better OR an upright FVC 30% or greater at Screening;
5. Patient, if sexually active, is willing to abstain from sexual intercourse or employ a barrier or medical method of contraception during and for 3 months following completion of IP administration;
6. Patient and patient's parent(s)/guardian(s) (if patient is <18 years of age) and/or caregiver(s) are willing and able to comply with scheduled visits, IP administration plan, and study procedures;
7. Patient must be on a stable dose of glucocorticoid (GC) or not treated with GC for at least 3 months prior to the first dose of IP and is expected to remain on stable dose of GC treatment or off GC for the duration of the study.

Other inclusion criteria may apply

Exclusion Criteria:

1. Patient has had an acute illness within 4 weeks prior to the first dose of IP;
2. Patient has evidence of symptomatic cardiomyopathy (New York Heart Association Class III or higher);
3. Patient requires ventilation support while awake during the day;
4. Patient has an allergy or hypersensitivity to IP or any of its constituents;
5. Patient has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the investigator;
6. Patient has a previous or ongoing medical condition, medical history, physical findings, or laboratory abnormalities that could affect patient 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;
7. Patient has had surgery within 3 months prior to the first anticipated administration of IP or has known plans to have surgery during the Treatment Period;
8. Patient has positive test results for hepatitis B antigen, hepatitis C antibody, or human immunodeficiency virus antibody at Screening;
9. Patient has been diagnosed with asthma that requires chronic treatment with a long-acting beta agonist;
10. Patient has relevant history of or current drug or alcohol abuse or use of any tobacco/marijuana products by smoking or vaping within 3 months prior to treatment with IP;
11. Patient is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to the first dose of IP or within 5 times the half-life of a medication, whichever is longer;
12. Patient has taken any gene therapy;
13. Patient is currently taking any other exon skipping agent or has taken any other exon skipping agent within 3 months prior to the first dose of IP;
14. Patient has hydronephrosis, hydroureter, renal or urinary tract calculi, or ureteral stenosis by renal ultrasound;
15. Patient was previously enrolled in an interventional study of viltolarsen.

Other exclusion criteria may apply

Contacts and Locations

Locations

United States, Virginia

Children's Hospital of Richmond at VCU

Richmond, Virginia, United States, 23219

China

The Third Medical Center of PLA General Hospital

Beijing, China, 1000053

Hunan Children's Hospital

Changsha, China, 410021

Italy

Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore

Roma, Italy, 00168

Russian Federation

Russian National Research Medical University

Moscow, Russian Federation, 117997

Saint Petersburg State Paediatric Medical University

Saint Petersburg, Russian Federation, 194100

Spain

Hospital Sant Joan de Deu

Barcelona, Spain, 08950

Turkey

Yeditepe University Kosuyolu Hospital

Istanbul, Turkey, 34718

Sponsors and Collaborators

NS Pharma, Inc.

Nippon Shinyaku Co., Ltd.

More Information

• Responsible Party: NS Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT04956289
• Other Study ID Numbers: NS-065/NCNP-01-211
• First Posted: July 9, 2021
• Last Update Posted: July 19, 2023
• Last Verified: July 2023

• 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; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked