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

Duchenne Muscular Dystrophy Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04060199
• Other study ID #: NS-065/NCNP-01-301
• Status: Completed
• Phase: Phase 3
• Start date: April 14, 2020
• Est. completion date: October 19, 2023

Study information

• Verified date: October 2023
• Source: NS Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: October 19, 2023
• Est. primary completion date: October 19, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 7 Years

Eligibility

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

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Viltolarsen
IV infusion
• Placebo
IV infusion

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
NS Pharma, Inc.	Nippon Shinyaku Co., Ltd.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Chile,  China,  Greece,  Hong Kong,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Norway,  Russian Federation,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TTSTAND	Change in Time to Stand (TTSTAND)	baseline to 48 weeks of treatment
Secondary	TTRW	Change in Time to Run/Walk 10 Meters Test (TTRW)	baseline to 48 weeks of treatment
Secondary	6MWT	Change in Six-minutes Walk Test (6MWT)	baseline to 48 weeks of treatment
Secondary	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
Secondary	TTCLIMB	Change in Time to Climb 4 Steps Test (TTCLIMB)	baseline to 48 weeks of treatment
Secondary	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