Study to Assess the Efficacy and Safety of Viltolarsen in Ambulant Boys With DMD (RACER53)

A Phase 3 Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Efficacy and Safety of Viltolarsen in Ambulant Boys With Duchenne Muscular Dystrophy (DMD)

The main objective of this study is to evaluate the efficacy of Viltolarsen compared to placebo in Duchenne muscular dystrophy (DMD) patients amenable to exon 53 skipping.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Placebo; Drug: Viltolarsen

Detailed Description

This is a Phase 3 randomized, double-blind, placebo-controlled, multi-center study to assess the efficacy and safety of Viltolarsen in ambulant boys with Duchenne muscular dystrophy. Eligible patients with out-of-frame deletion mutations amenable to exon 53 skipping will be randomized to receive once weekly intravenous (IV) infusions of 80 mg/kg Viltolarsen or placebo for up to 48 weeks.

The study will enroll approximately 74 patients amenable to exon 53 skipping. Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests such as Time to Stand Test (TTSTAND), Time to Run/Walk 10 Meters Test (TTRW), Six-minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), Time to Climb 4 Steps Test (TTCLIMB) and Hand-held dynamometer (elbow extension, elbow flexion, knee extension and knee flexion on the dominant side only).

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

Blood samples will be taken periodically throughout the study to assess the pharmacokinetics of study drug.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Trial Info; Phone Number: 1-866-677-4276; Email: trialinfo@nspharma.com

Study Locations

• Australia
  • Brisbane, Australia
    • Queensland Children's Hospital
  • Nedlands, Australia
    • Perth Children's Hospital
  • Westmead, Australia
    • The Childrens Hospital at Westmead
• Canada
  • Calgary, Canada
    • Alberta Children's Hospital
  • Quebec City, Canada
    • CHU de Quebec Research Centre
  • Ontario
    • Toronto, Ontario, Canada
      • The Hospital for Sick Children (SickKids)
• Chile
  • Santiago, Chile
    • Pontificia Universidad Catolica de Chile
  • Santiago, Chile
    • Hospital de Niños Roberto del Rio
• China
  • Beijing, China
    • Chinese PLA General Hospital
  • Beijing, China
    • The Third Medical Center of PLA General Hospital
  • Changsha, China
    • Hunan Children's Hospital
  • Shanghai, China
    • Children's Hospital of Fudan University
  • Shenzhen, China
    • Shenzhen Children's Hospital
• Greece
  • Athens, Greece
    • AGIA SOFIA Children's Hospital
  • Thessaloníki, Greece
    • Hippokration General Hospital of Thessaloniki
• Hong Kong
  • Kowloon Bay, Hong Kong
    • Hong Kong Children's Hospital
• Italy
  • Rome, Italy
    • Fondazione Policlinico Universitario A. Gemelli - Universita Cattolica del Sacro Cuore
• Korea, Republic of
  • Pusan, Korea, Republic of
    • Pusan National University Yangsan Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
• Mexico
  • Chihuahua, Mexico
    • Hospital Angeles Chihuahua
  • Ciudad de mexico, Mexico
    • Instituto Nacional de Pediatría
• Netherlands
  • Leiden, Netherlands
    • Leids Universitair Medisch Centrum
  • Gelderland
    • Nijmegen, Gelderland, Netherlands
      • Radboud Universitair Medisch Centrum
• New Zealand
  • Auckland, New Zealand
    • New Zealand Clinical Research Ltd
• Norway
  • Oslo, Norway
    • Rikshospitalet
• Russian Federation
  • Moscow, Russian Federation
    • Russian National Research Medical University n.a. N.I.Pirogov, structural branch - Research Clinical Institute of Pediatrics n.a. Academician Yu. E. Veltishchev
  • Saint Petersburg, Russian Federation
    • "Saint Petersburg State Paediatric Medical University" based at Consultative and Diagnostic Centre
  • Tomsk, Russian Federation
    • Tomsk National Research Medical Center of Russian Academy of Sciences
• Spain
  • Barcelona, Spain
    • Hospital Sant Joan de Deu
  • Madrid, Spain
    • Hospital Universitario La Paz
• Taiwan
  • Kaohsiung, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
• Turkey
  • Istanbul, Turkey
    • Yeditepe University Kosuyolu Hospital
• Ukraine
  • Kyiv, Ukraine
    • State Institution "Ukrainian Medical rehabilitation Center for Children with organic disorders of the nervous system of the Ministry of Health of Ukraine"
• United Kingdom
  • Birmingham, United Kingdom
    • Birmingham Heartlands Hospital
  • Glasgow, United Kingdom
    • Royal Hospital for Children - Glasgow
  • London, United Kingdom
    • University College London Institute of Child Health
  • Manchester, United Kingdom
    • Royal Manchester Children's Hospital
• United States
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H. Lurie Children's Hospital of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male ≥ 4 years and < 8 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
• TTSTAND < 10 seconds
• Stable dose of glucocorticoid (GC) for at least 3 months prior to study entry and is expected to remain on stable dose of GC treatment for the duration of the study
• Other inclusion criteria may apply

Exclusion Criteria:

• Current or history of chronic systemic fungal or viral infections
• Acute illness within 4 weeks prior to the first dose of study drug
• Evidence of symptomatic cardiomyopathy (Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary)
• Allergy or hypersensitivity to the study drug or to any of its constituents
• 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;
• Surgery within the 3 months prior to the first dose of study drug or surgery is planned for anytime during the duration of the study
• Participant has positive test results for hepatitis B antigen, hepatitis C antibody or human immunodeficiency virus (HIV)
• Currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to the first dose of study drug or within 5 times the half-life of a medication, whichever is longer
• Previously enrolled in an interventional study of viltolarsen
• Currently taking any other exon skipping agent or has taken any other exon skipping agent within 3 months prior to the first dose of study drug
• Having taken any gene therapy
• Other exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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; IV infusion; Other Names: NS-065/NCNP-01
Placebo Comparator: Placebo; Patients amenable to exon 53 skipping will receive placebo intravenous (IV) infusions, weekly, for up to 48 weeks.	Drug: Placebo; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TTSTAND	Change in Time to Stand (TTSTAND)	baseline to 48 weeks of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TTRW	Change in Time to Run/Walk 10 Meters Test (TTRW)	baseline to 48 weeks of treatment
6MWT	Change in Six-minutes Walk Test (6MWT)	baseline to 48 weeks of treatment
NSAA	Change in North Star Ambulatory Assessment (NSAA) 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 to 48 weeks of treatment
TTCLIMB	Change in Time to Climb 4 Steps Test (TTCLIMB)	baseline to 48 weeks of treatment
Hand-held dynamometer	The force generated for each muscle strength (elbow extension, elbow flexion, knee extension, and knee flexion on the dominant side only) will be measured by Hand-held dynamometer.	baseline to 48 weeks of treatment

Collaborators and Investigators

• Sponsor: NS Pharma, Inc.
• Collaborators: Nippon Shinyaku Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2020
• Primary Completion (Actual): October 19, 2023
• Study Completion (Actual): October 19, 2023

Study Registration Dates

• First Submitted: August 15, 2019
• First Submitted That Met QC Criteria: August 15, 2019
• First Posted (Actual): August 19, 2019

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 25, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: NS-065/NCNP-01-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No