Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD)

Duchenne Muscular Dystrophy Clinical Trial

— ESSENCE  

Official title:

A Double-Blind, Placebo-Controlled, Multi-Center Study With an Open-Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients With Duchenne Muscular Dystrophy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02500381
• Other study ID #: 4045-301
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 28, 2016
• Est. completion date: October 3, 2025

Study information

• Verified date: March 2024
• Source: Sarepta Therapeutics, 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 SRP-4045 (casimersen) and SRP-4053 (golodirsen) compared to placebo in participants with DMD with out-of-frame deletion mutations amenable to skipping exon 45 and exon 53, respectively.

Description:

This is a double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of SRP-4045 and SRP-4053. Eligible participants with out-of-frame deletion mutations amenable to exon 45 or 53 skipping will be randomized to receive once weekly intravenous (IV) infusions of 30 milligrams/kilograms (mg/kg) SRP-4045 or 30 mg/kg SRP-4053 respectively (combined-active group) or placebo for up to 96 weeks (the placebo-controlled period of the trial). This will be followed by an open-label extension period in which all participants will receive open-label active treatment for 48 weeks (up to Week 144 of study). The study will enroll approximately 222 participants. Twice as many participants will be randomized to receive active treatment as will receive placebo (2:1 randomization). Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests, such as the 6-minute walk test (6MWT). All participants will undergo a muscle biopsy at baseline and a second muscle biopsy either at Week 48 or Week 96. Safety will be assessed through the collection of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations throughout the study. Blood samples will be taken periodically throughout the study to assess the pharmacokinetics of both drugs.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 228
• Est. completion date: October 3, 2025
• Est. primary completion date: October 3, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 6 Years to 13 Years

Eligibility

Inclusion Criteria:

• Genotypically confirmed DMD, with genetic deletion amenable to exon 45 or exon 53 skipping
• Stable dose of oral corticosteroids for at least 24 weeks prior to Week 1, and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight).
• Intact right and left biceps or 2 alternative upper muscle groups
• Mean 6MWT =300 meters and =450 meters
• Stable pulmonary function: forced vital capacity (FVC) =50% predicted

Exclusion Criteria:

• Treatment with gene therapy at any time
• Previous treatment with SMT C1100 within 1 week prior to Week 1 and previous treatment with PRO045 (BMN 045), PRO053 (BMN 053), or PRO051 (BMN 051) within 24 weeks prior to Week 1
• Current or previous treatment with any other experimental treatment within 12 weeks prior to Week 1
• Major surgery within 3 months prior to Week 1
• Presence of other clinically significant illness Other inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

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

Intervention

Drug:
• SRP-4045
SRP-4045 solution for IV infusion
• SRP-4053
SRP-4053 solution for IV infusion
• Placebo
SRP-4045 or SRP-4053 placebo-matching solution for IV infusion

Locations

Country	Name	City	State
Argentina	DOM Centro de Reumatologia	Ciudad Autonoma de Buenos Aires
Australia	Royal Children's Hospital Melbourne	Parkville	Victoria
Australia	Queensland Children's Hospital	South Brisbane
Australia	Children's Hospital at Westmead	Westmead
Belgium	Universitair Ziekenhuis Gent	Ghent
Belgium	Universitair Ziekenhuis Leuven	Leuven
Belgium	CHR de la Citadelle	Liège
Bulgaria	University Multiprofile Hospital for Active Treatment Aleksandrovska EAD	Sofia	Sofia-Grad
Canada	Alberta Childrens Hospital	Calgary	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Children's and Women's Health Centre of British Columbia	Vancouver	British Columbia
Czechia	University Hospital Brno	Brno
Czechia	Fakultni nemocnice v Motole	Praha
Denmark	Rigshospitalet Copenhagen University Hospital	København Ø
France	Reference Centre for Neuromuscular Diseases	Nantes
France	Hôpital Armand Trousseau	Paris
France	Hôpital Des Enfants	Toulouse	Haute-Garonne
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Essen	Essen
Germany	University Hospital Freiburg	Freiburg
Greece	IASO Children's Hospital	Maroussi
Greece	Ippokratio General Hospital of Thessaloniki	Thessaloniki
Hungary	Semmelweis Egyetem Genomikai Medicina és Ritka Betegsegek Intezete	Budapest
India	Royal Instituite of Child Neurosciences	Ahmedabad	Gujarat
India	Deenanth Mangeshkar Hospital	Pune	Maharashtra
Ireland	The Children's University Hospital	Dublin
Israel	Schneider Children's Medical Center of Israel	Petah Tikvah
Italy	Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant' Anna	Ferrara
Italy	Istituto Giannina Gaslini	Genoa
Italy	Az Ospedaliera Universitaria Policlinico G Martino	Messina
Italy	Fondazione IRCCS Istituto Neurologico Carlo Besta	Milano
Italy	Policlinico Universitario A Gemelli	Rome
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan
Mexico	Neurociencias Estudios Clínicos S.C	Culiacán
Mexico	Instituto de Investigaciones Clínicas para la Salud A.C	Durango
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Samodzielny Publiczny Centralny Szpital Kliniczny	Warsaw	Mazowieckie
Russian Federation	Federal state budget educational institution of higher education "Russian national research medical university n.a. N.I. Pirogov" of Ministry of healthcare of Russian Federation	Moscow
Russian Federation	State Autonomous Healthcare Institution of Sverdlovsk Region Children's Clinical Hospital No. 9 City of Ekaterinburg	Yekaterinburg
Serbia	Clinic for Neurology and Psychiatry for Children and Youth	Belgrade
Spain	Hospital de La Santa Creu i Sant Pau	Barcelona
Spain	Hospital Sant Joan de Deu	Barcelona
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Sweden	Drottning Silvias Barn Och Ungdomssjukhus	Göteborg
United Kingdom	Royal Hospital for Children (Glasgow)	Glasgow
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds
United Kingdom	Alder Hey Childrens Hospital	Liverpool
United Kingdom	Great Ormond Street Hospital (GOSH)	London
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne
United Kingdom	John Radcliffe Hospital	Oxford
United States	Center for Integrative Rare Disease Research (CIRDR)	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center (CCHMC)	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Medical Center Dallas	Dallas	Texas
United States	University of Florida	Gainesville	Florida
United States	NW Florida Clinical Research Group, LLC	Gulf Breeze	Florida
United States	University of Iowa Children's Hospital	Iowa City	Iowa
United States	University of Kansas, Medical Center	Kansas City	Kansas
United States	Las Vegas Clinic	Las Vegas	Nevada
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	David Geffen School of Medicine, UCLA	Los Angeles	California
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Neuromuscular Research Center	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Shriners Hospital for Children	Portland	Oregon
United States	University of Rochester Clinical Research Center	Rochester	New York
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	Rady Children's Hospital San Diego/ UCSD	San Diego	California
United States	Stanford University School of Medicine/Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Sarepta Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  India,  Ireland,  Israel,  Italy,  Korea, Republic of,  Mexico,  Poland,  Russian Federation,  Serbia,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Total Distance Walked During 6MWT at Week 96		Baseline, Week 96
Secondary	Change from Baseline in the Total Distance Walked During 6MWT at Week 144 (Week 48 of the Open-Label Extension Period)		Baseline, Week 144
Secondary	Change from Baseline in Dystrophin Protein Levels Determined by Western Blot at Weeks 48 or 96		Baseline, Week 48 or Week 96
Secondary	Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Weeks 48 or 96		Baseline, Week 48 or Week 96
Secondary	Participant's Ability to Rise Independently From the Floor, as indicated by a North Star Ambulatory Assessment (NSAA) Subscore	The NSAA is a clinician administered scale that rates the participant's performance on various functional activities. During this assessment, the participant's ability to rise independently from the floor (without external support) will be reported as an NSAA subscore of "2" (without modification) or "1" (Gower's maneuver).	Week 96, Week 144
Secondary	Time to Loss of Ambulation (LOA)		Baseline, Week 96, and Week 144
Secondary	Change From Baseline in the NSAA Total Score at Week 96 and Week 144	The NSAA is a clinician administered scale that rates the participant's performance on various functional activities. During this assessment, participants will be asked to perform 17 different functional activities, including a 10 meter walk/run, rising from a sit to standing, standing on 1 leg, climbing a box step, descending a box step, rising from lying to sitting, rising from the floor, lifting the head, standing on heels, and jumping. Participants will be graded as follows: 2 = achieves goal without any assistance; 1 = modified method but achieves goal independent of physical assistance from another person; and 0 = unable to achieve goal independently. NSAA Total Score ranges from 0 to 34, with a score of 34 implying normal function.	Baseline, Week 96 and Week 144
Secondary	Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 96 and Week 144		Baseline, Week 96 and Week 144