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

Phase 3

Completed

• Conditions: Duchenne Muscular Dystrophy
• Interventions: Drug: Placebo; Drug: Viltolarsen

• Registration Number: NCT04060199
• Lead Sponsor: NS Pharma, Inc.

Brief 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.

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 Timeline

• Study First Submitted: 2019-08-15
• Study First Submitted QC: 2019-08-15
• Study First Posted: 2019-08-19
• Study Start: 2020-04-14
• Primary Completion: 2023-10-19
• Study Completion: 2023-10-19
• Status Verified: 2024-10
• Results First Submitted: 2024-10-17
• Results First Submitted QC: 2024-12-03
• Last Update Submitted: 2024-12-03
• Results First Posted: 2024-12-11
• Last Update Posted: 2024-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 77

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Patients amenable to exon 53 skipping will receive placebo intravenous (IV) infusions, weekly, for up to 48 weeks.
Viltolarsen	Viltolarsen	Patients amenable to exon 53 skipping will receive viltolarsen intravenous (IV) infusions, weekly, at 80 mg/kg for up to 48 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Time to Stand (TTSTAND) Velocity	baseline, Week 13, 25, 37, 49	The change from baseline for velocity converted from TTSTAND was compared between the viltolarsen-treated patients and the placebo-treated patients. TTSTAND was assessed as the time it takes the participant to go from lying flat on the floor to standing. The time measured for TTSTAND was converted to a velocity expressed as rise per second.

Trial Locations

Locations (40)

The Childrens Hospital at Westmead; 🇦🇺 Westmead, Australia

Birmingham Heartlands Hospital; 🇬🇧 Birmingham, United Kingdom

Kaohsiung Medical University Chung-Ho Memorial Hospital; 🇨🇳 Kaohsiung, Taiwan

Instituto Nacional de Pediatria; 🇲🇽 Ciudad de mexico, Mexico

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Hospital Angeles Chihuahua; 🇲🇽 Chihuahua, Mexico

Radboud Universitair Medisch Centrum; 🇳🇱 Nijmegen, Gelderland, Netherlands

Chinese PLA General Hospital; 🇨🇳 Beijing, China

Hunan Children's Hospital; 🇨🇳 Changsha, China

The Third Medical Center of PLA General Hospital; 🇨🇳 Beijing, China

Children's Hospital of Fudan University; 🇨🇳 Shanghai, China

Queensland Children's Hospital; 🇦🇺 Brisbane, Australia

Perth Children's Hospital; 🇦🇺 Nedlands, Australia

Hospital de Niños Roberto del Rio; 🇨🇱 Santiago, Chile

Alberta Children's Hospital; 🇨🇦 Calgary, Canada

CHU de Quebec Research Centre; 🇨🇦 Quebec City, Canada

Pontificia Universidad Católica de Chile; 🇨🇱 Santiago, Chile

Agia Sofia Children's Hospital; 🇬🇷 Athens, Greece

Shenzhen Children's Hospital; 🇨🇳 Shenzhen, China

Hippokration General Hospital of Thessaloniki; 🇬🇷 Thessaloníki, Greece

Fondazione Policlinico Universitario A. Gemelli - Universita Cattolica del Sacro Cuore; 🇮🇹 Rome, Italy

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

Leids Universitair Medisch Centrum; 🇳🇱 Leiden, Netherlands

Rikshospitalet; 🇳🇴 Oslo, Norway

New Zealand Clinical Research Ltd; 🇳🇿 Auckland, New Zealand

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, Russian Federation

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Sant Joan de Deu; 🇪🇸 Barcelona, Spain

Yeditepe University Kosuyolu Hospital; 🇹🇷 Istanbul, Turkey

State Institution "Ukrainian Medical rehabilitation Center for Children with organic disorders of the nervous system of the Ministry of Health of Ukraine"; 🇺🇦 Kyiv, Ukraine

Royal Manchester Children's Hospital; 🇬🇧 Manchester, United Kingdom

Royal Hospital for Children - Glasgow; 🇬🇧 Glasgow, United Kingdom

University College London Institute of Child Health; 🇬🇧 London, United Kingdom

Pusan National University Yangsan Hospital; 🇰🇷 Pusan, Korea, Republic of

University of California Davis Medical Center; 🇺🇸 Sacramento, California, United States

Ann and Robert H. Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

The Hospital for Sick Children (SickKids); 🇨🇦 Toronto, Ontario, Canada

Hong Kong Children's Hospital; 🇭🇰 Kowloon Bay, Hong Kong