Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD)
- Conditions
- Duchenne Muscular Dystrophy
- Interventions
- Drug: SRP-4045Drug: SRP-4053Drug: Placebo
- Registration Number
- NCT02500381
- Lead Sponsor
- Sarepta Therapeutics, Inc.
- Brief 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.
- Detailed 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 & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 228
- 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 brachii muscles or 2 alternative upper arm muscle groups
- Mean 6MWT ≥300 meters and ≤450 meters
- Stable pulmonary function: forced vital capacity (FVC) ≥50% predicted
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo followed by SRP-4045 or SRP-4053 Placebo Participants amenable to exon 45 or 53 skipping will receive SRP-4045 or SRP-4053 placebo-matching IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study). Placebo followed by SRP-4045 or SRP-4053 SRP-4053 Participants amenable to exon 45 or 53 skipping will receive SRP-4045 or SRP-4053 placebo-matching IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study). SRP-4053 SRP-4053 Participants amenable to exon 53 skipping will receive SRP-4053 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study). SRP-4045 SRP-4045 Participants amenable to exon 45 skipping will receive SRP-4045 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study). Placebo followed by SRP-4045 or SRP-4053 SRP-4045 Participants amenable to exon 45 or 53 skipping will receive SRP-4045 or SRP-4053 placebo-matching IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
- Primary Outcome Measures
Name Time Method Change From Baseline in the 4-Step Ascend Velocity at Week 96 Baseline, Week 96
- Secondary Outcome Measures
Name Time Method Change from Baseline in the Total Distance Walked During 6MWT at Week 96 Baseline, Week 96 Change from Baseline in Rise from Floor Velocity at Week 96 Baseline, Week 96 Change From Baseline in the 4-Step Ascend Velocity at Week 144 Baseline, Week 144 Change From Baseline in Total Distance Walked During the 10-meter walk/run (10-MWR) Velocity Baseline, Week 96 Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 96 Baseline, Week 96 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.
Change from Baseline in Dystrophin Protein Levels Determined by Western Blot at Weeks 48 or 96 Baseline, Week 48 or Week 96 Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Weeks 48 or 96 Baseline, Week 48 or Week 96
Trial Locations
- Locations (75)
University of Florida
🇺🇸Gainesville, Florida, United States
University Hospital Brno
🇨🇿Brno, Czechia
Reference Centre for Neuromuscular Diseases
🇫🇷Nantes, France
Drottning Silvias Barn Och Ungdomssjukhus
🇸🇪Göteborg, Sweden
Royal Hospital for Children (Glasgow)
🇬🇧Glasgow, United Kingdom
Great Ormond Street Hospital (GOSH)
🇬🇧London, United Kingdom
Royal Victoria Infirmary
🇬🇧Newcastle upon Tyne, United Kingdom
Hôpital Armand Trousseau
🇫🇷Paris, France
Hospital Sant Joan de Deu
🇪🇸Barcelona, Spain
Fakultni nemocnice v Motole
🇨🇿Praha, Czechia
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
Schneider Children's Medical Center of Israel
🇮🇱Petah Tikvah, Israel
Neurociencias Estudios Clínicos S.C
🇲🇽Culiacán, Mexico
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
Neuromuscular Research Center
🇺🇸Phoenix, Arizona, United States
Shriners Hospital for Children
🇺🇸Portland, Oregon, United States
Children's Hospital of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Children's Hospital at Westmead
🇦🇺Westmead, Australia
Queensland Children's Hospital
🇦🇺South Brisbane, Australia
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
Hospital de La Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Alder Hey Childrens Hospital
🇬🇧Liverpool, United Kingdom
John Radcliffe Hospital
🇬🇧Oxford, United Kingdom
Stanford University School of Medicine/Medical Center
🇺🇸Stanford, California, United States
University of Rochester Clinical Research Center
🇺🇸Rochester, New York, United States
Children's Hospital of the King's Daughters
🇺🇸Norfolk, Virginia, United States
University of Iowa Children's Hospital
🇺🇸Iowa City, Iowa, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Cincinnati Children's Hospital Medical Center (CCHMC)
🇺🇸Cincinnati, Ohio, United States
David Geffen School of Medicine, UCLA
🇺🇸Los Angeles, California, United States
Children's Medical Center Dallas
🇺🇸Dallas, Texas, United States
Rady Children's Hospital San Diego/ UCSD
🇺🇸San Diego, California, United States
Center for Integrative Rare Disease Research (CIRDR)
🇺🇸Atlanta, Georgia, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Ann and Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
University of Kansas, Medical Center
🇺🇸Kansas City, Kansas, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Rigshospitalet Copenhagen University Hospital
🇩🇰København Ø, Denmark
Las Vegas Clinic
🇺🇸Las Vegas, Nevada, United States
NW Florida Clinical Research Group, LLC
🇺🇸Gulf Breeze, Florida, United States
DOM Centro de Reumatologia
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
🇧🇬Sofia, Sofia-Grad, Bulgaria
IASO Children's Hospital
🇬🇷Maroussi, Greece
The Children's University Hospital
🇮🇪Dublin, Ireland
Az Ospedaliera Universitaria Policlinico G Martino
🇮🇹Messina, Italy
Alberta Childrens Hospital
🇨🇦Calgary, Alberta, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
Universitair Ziekenhuis Gent
🇧🇪Ghent, Belgium
Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant' Anna
🇮🇹Ferrara, Italy
Instituto de Investigaciones Clínicas para la Salud A.C
🇲🇽Durango, Mexico
Clinic for Neurology and Psychiatry for Children and Youth
🇷🇸Belgrade, Serbia
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
University of Utah
🇺🇸Salt Lake City, Utah, United States
Children's and Women's Health Centre of British Columbia
🇨🇦Vancouver, British Columbia, Canada
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
University Hospital Freiburg
🇩🇪Freiburg, Germany
Ippokratio General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Istituto Giannina Gaslini
🇮🇹Genoa, Italy
Fondazione IRCCS Istituto Neurologico Carlo Besta
🇮🇹Milano, Italy
CHR de la Citadelle
🇧🇪Liège, Belgium
Hôpital Des Enfants
🇫🇷Toulouse, Haute-Garonne, France
St. Louis Children's Hospital
🇺🇸Saint Louis, Missouri, United States
Universitair Ziekenhuis Leuven
🇧🇪Leuven, Belgium
Universitätsklinikum Essen
🇩🇪Essen, Germany
Policlinico Universitario A Gemelli
🇮🇹Rome, Italy
Pusan National University Yangsan Hospital
🇰🇷Yangsan, Korea, Republic of
State Autonomous Healthcare Institution of Sverdlovsk Region Children's Clinical Hospital No. 9 City of Ekaterinburg
🇷🇺Yekaterinburg, Russian Federation
Royal Children's Hospital Melbourne
🇦🇺Parkville, Victoria, Australia
Semmelweis Egyetem Genomikai Medicina és Ritka Betegsegek Intezete
🇭🇺Budapest, Hungary
Royal Instituite of Child Neurosciences
🇮🇳Ahmedabad, Gujarat, India
Samodzielny Publiczny Centralny Szpital Kliniczny
🇵🇱Warsaw, Mazowieckie, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Deenanth Mangeshkar Hospital
🇮🇳Pune, Maharashtra, India