Study of SRP-4045 and SRP-4053 in DMD Patients

study id #: NCT02500381

condition: Duchenne Muscular Dystrophy

status: recruiting

The main objective of this study is to evaluate the efficacy of SRP-4045 and SRP-4053 compared to placebo in Duchenne muscular dystrophy (DMD) patients with out-of-frame deletion mutations amenable to skipping exon 45 and exon 53, respectively.

intervention: SRP-4045, SRP-4053, Placebo

mechanism of action: Exon-skipping to promote dystrophin production

results: https://clinicaltrials.gov/ct2/show/results/NCT02500381

last updated: February 14, 2020

start date: September 28, 2016

estimated completion: May 2022

phase of development: Phase 3

size / enrollment: 222

study description:
This is a double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of SRP-4045 and SRP-4053. Eligible patients 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 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 patients will receive open-label active treatment for 48 weeks (up to Week 144 of study).
The study will enroll approximately 222 patients, with a planned minimum target of 111 patients amenable to exon 45 skipping and 111 patients amenable to exon 53 skipping.
Approximately 148 patients will be randomized to receive active treatment with either SRP-4045 or SRP-4053 (depending on deletion mutation), and 74 patients will be randomized to receive placebo. Twice as many patients will 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 six-minute walk test (6MWT). All patients 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.

primary outcomes:

• Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 96 [ Time Frame: Baseline and Week 96 ]

secondary outcomes:

• Change from Baseline the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 144 (Week 48 of the OL period) [ Time Frame: Baseline, Week 144 ]
  
• Change from Baseline in Dystrophin Protein Levels Determined by Western Blot at Weeks 48 or 96 [ Time Frame: Baseline and Weeks 48 or 96 ]
  
• Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Weeks 48 or 96 [ Time Frame: Baseline and Weeks 48 or 96 ]
  
• Ability to Rise Independently From the Floor [ Time Frame: Week 96, Week 144 ]
  
• Time to Loss of Ambulation (LOA) [ Time Frame: Baseline, Week 96, Week 144 ]
  
• Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 96 and Week 144 [ Time Frame: Baseline, Week 96, Week 144 ]
  The NSAA is a functional scale devised from the Hammersmith Scale of Motor Ability specifically 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). The scale assesses activities required to remain functionally ambulant (example, rise from the floor), activities that can be difficult even early in the disease (e.g. standing on heels) and activities that are known to progressively deteriorate over time (stand from a chair, walk). NSAA Total Score ranges from 0 to 34, with a score of 34 implying normal function.
  
• Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 96 and Week 144 [ Time Frame: Baseline, Week 96, Week 144 ]

inclusion criteria:

exclusion criteria:
• Treatment with gene therapy at any time
• Previous treatment with SMT C1100, 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 (other than deflazacort) within 12 weeks prior to Week 1
• Major surgery within 3 months prior to Week 1
• Presence of other clinically significant illness

sponsor: Sarepta Therapeutics, Inc

contacts: 1-888-727-3782, clinicaltrials@sarepta.com

• United States, Arizona
  Neuromuscular Research Center
  
  
• United States, California
  Children’s Hospital Los Angeles
  
  
• United States, California
  David Geffen School of Medicine at UCLA
  
  
• United States, California
  Rady Children’s Hospital, UCSD
  
  
• United States, California
  Stanford University School of Medicine/Medical Center
  
  
• United States, California
  University of California Davis Medical Center
  
  
• United States, Connecticut
  Connecticut Children’s Medical Center
  
  
• United States, Florida
  Northwest Florida Clinical Research Group, LLC
  
  
• United States, Florida
  University of Florida
  
  
• United States, Georgia
  Center for Integrative Rare Disease Research (CIRDR)
  
  
• United States, Illinois
  Ann & Robert H. Lurie Children’s Hospital of Chicago
  
  
• United States, Iowa
  University of Iowa Stead Family Children’s Hospital
  
  
• United States, Kansas
  University of Kansas Medical Center
  
  
• United States, Massachusetts
  Boston Children’s Hospital
  
  
• United States, Missouri
  St. Louis Children’s Hospital
  
  
• United States, Nevada
  Las Vegas Clinic
  
  
• United States, New York
  University of Rochester Clinical Research Center
  
  
• United States, Ohio
  Cincinnati Children’s Hospital Medical Center
  
  
• United States, Ohio
  Nationwide Children’s Hospital
  
  
• United States, Oregon
  Shriners Hospital for Children
  
  
• United States, Pennsylvania
  Children’s Hospital of Philadelphia
  
  
• United States, Pennsylvania
  UPMC Children’s Hospital of Pittsburgh
  
  
• United States, Texas
  Children’s Medical Center Dallas
  
  
• United States, Utah
  University of Utah
  
  
• United States, Virginia
  Children’s Hospital of the King’s Daughters
  
  
• United States, Wisconsin
  Children’s Hospital of Wisconsin
  
  
• Australia, New South Wales
  The Childrens Hospital at Westmead
  Kaitlyn Griffin, 6-129-845-0495, kaitlyn.griffin@health.nsw.gov.au
  
  
• Australia, Victoria
  Royal Children’s Hospital Melbourne
  Jemima Mitchell, 6-139-936-6157, jemima.mitchell@rch.org.au
  
  
• Belgium
  CHR Citadelle
  Laura Buscemi, 324-321-8322, laura.buscemi@chuliege.be
  
  
• Belgium
  Universitair Ziekenhuis Gent
  Elke Vos, 329-332-1954, elke.devos@uzgent.be
  
  
• Belgium
  Universitair Ziekenhuis Leuven
  Anne Eynden, 321-634-3991, anne.vandeneynden@uzleuven.be
  
  
• Bulgaria, Sofia-Grad
  University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
  Tanya Dimitrova, 35-988-932-0421, taniadimi@abv.bg
  
  
• Canada, Alberta
  Alberta Children’s Hospital
  Trevor Rutschmann, 403-955-3192, trevor.Rutschmann@albertahealthservices.com
  
  
• Canada, British Columbia
  Children’s and Women’s Health Centre of British Columbia
  Conrado Guzman, 604-875-2345 xext 6834, conrado.deguzman@cw.bc.ca
  
  
• Canada, Ontario
  London Health Sciences Centre
  Gina Bhullar, 519-685-8500 ext 55058, gina.bhullar@lhsc.on.ca
  
  
• Czechia
  Fakultni nemocnice v Motole
  Marcela Hlozankova, 42-022-443-3367, m.hlozankova@centrum.cz
  
  
• Czechia
  University Hospital Brno
  
  
• France
  Hopital Armand Trousseau
  Dominique Duchêne, 3-317-173-8313, d.duchene@institut-myologie.org
  
  
• France
  Hôpital des enfants
  Françoise Auriol, 3-353-455-8589, auriol.f@chu-toulouse.fr
  
  
• France
  Reference Centre for Neuromuscular Diseases
  Christelle Peseux, 3-324-008-7880, christelle.peseux@chu-nantes.fr
  
  
• Germany
  LMU Klinikum der Universität München
  Astrid Blaschek, 498-944-005-5110, astrid.blaschek@med.uni-muenchen.de
  
  
• Germany
  University Hospital Freiburg
  Sabine Wider, 497-612-704-3440, sabine.wider@uniklinik-freiburg.de
  
  
• Germany
  Universitätsklinikum Essen
  Corinna Seifert, 492-017-238-5170, corinna.seifert@uk-essen.de 
  
  
• Hungary
  Semmelweis Egyetem Genomikai Medicina és Ritka Betegsegek Intezete
  Noemi Toreki, 361-459-1492, tnoemy@gmail.com
  
  
• Israel
  Schneider Children’s Medical Center of Israel
  Ori Raz, 972-525-1860 x44, orira1@clalit.org.il
  
  
• Italy
  Az Ospedaliera Universitaria Policlinico G Martino
  Daniela Quattrocchi, 39-349-350-0123, danifour@alice.it
  
  
• Italy
  Azienda Ospedaliero – Universitaria di Ferrara – Arcispedale Sant’ Anna
  Fernanda Fortunato, 39-346-537-4262, frtfnn@unife.it
  
  
• Italy
  Fondazione Policlinico Universitario A Gemelli
  Mariarosaria Vizzino, 39-063-015-8581, npi.clinicaltrials@rm.unicatt.it
  
  
• Italy
  Istituto Giannina Gaslini
  Marina Pedemonte, 390-105-636-2675, marinapedemonte@gaslini.org 
  
  
• Poland, Mazowieckie
  Samodzielny Publiczny Centralny Szpital Kliniczny
  Aleksandra Jastrzebska, 4-850-363-3513, aleksandra.n.jastrzebska@gmail.com
  
  
• Spain
  Hospital Sant Joan de Deu
  Marina Garcia, 3-493-600-9733 , mgarciago@fsjd.org
  
  
• Spain
  Hospital Universitari i Politecnic La Fe Valencia
  Pilar Marti, 3-496-124-4000, mapifres@gmail.com 
  
  
• Spain
  Hospital de La Santa Creu i Sant Pau
  Nuria Vidal, 3-493-553-7115, nvidalf@santpau.cat
  
  
• Sweden
  Drottning Silvias Barn Och Ungdomssjukhus
  Anna-Lena Tulinius , 4-631-343-6069, anna-lena.tulinius@vgregion.se
  
  
• United Kingdom
  Alder Hey Children’s NHS Foundation Trust
  Timothy Henderson, 44-151-252-5164, Timothy.Henderson@alderhey.nhs.uk 
  
  
• United Kingdom
  Great Ormond Street Hospital (GOSH)
  
  
• United Kingdom
  Royal Victoria Infirmary
  Valerie Corrall, 440-191-208-4569, valerie.corrall@ncl.ac.uk 
  
  
• United Kingdom
  The Leeds Teaching Hospitals NHS Trust
  Heather Rostron