Study of SRP-4045 and SRP-4053 in DMD Patients (ESSENCE)
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| ClinicalTrials.gov Identifier: NCT02500381 |
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Recruitment Status :
Recruiting
First Posted : July 16, 2015
Last Update Posted : December 3, 2018
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Sponsor:
Sarepta Therapeutics
Information provided by (Responsible Party):
Sarepta Therapeutics
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Duchenne Muscular Dystrophy | Drug: SRP-4045 Drug: SRP-4053 Drug: Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 222 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Masking Description: | Part 1 is double-blind and randomized; Part 2 is open-label. |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | September 28, 2016 |
| Estimated Primary Completion Date : | May 2022 |
| Estimated Study Completion Date : | May 2023 |
Resource links provided by the National Library of Medicine
Genetics Home Reference related topics:
Duchenne and Becker muscular dystrophy
MedlinePlus related topics:
Muscular Dystrophy
| Arm | Intervention/treatment |
|---|---|
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Experimental: SRP-4045
Patients amenable to exon 45 skipping will receive SRP-4045 intravenous (IV) infusions, weekly, at 30 mg/kg for up to 96 weeks in double-blinded period. This will be followed by an open label extension period in which all patients will receive open-label active treatment of SRP-4045 at 30 mg/kg/week IV infusions for 48 weeks in OL period (up to Week 144 in study).
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Drug: SRP-4045
SRP-4045 solution for IV infusion |
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Experimental: SRP-4053
Patients amenable to exon 53 skipping will receive SRP-4053 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in double-blinded period. This will be followed by an open label extension period in which all patients will receive open-label active treatment of SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks in OL period (up to Week 144 in study).
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Drug: SRP-4053
SRP-4053 solution for IV infusion |
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Placebo Comparator: Placebo followed by SRP-4045 or SRP-4053
Patients 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 double-blinded period. This will be followed by an open label extension period in which all patients will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV for 48 weeks in OL period (up to Week 144 in study).
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Drug: SRP-4045
SRP-4045 solution for IV infusion Drug: SRP-4053 SRP-4053 solution for IV infusion Drug: Placebo SRP-4045 or SRP-4053 placebo-matching solution for IV infusion |
Primary Outcome Measures :
- Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 96 [ Time Frame: Baseline and Week 96 ]
Secondary Outcome Measures :
- 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 ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 7 Years to 13 Years (Child) |
| Sexes Eligible for Study: | Male |
| Gender Based Eligibility: | Yes |
| Accepts Healthy Volunteers: | No |
Criteria
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
- Intact right and left biceps or 2 alternative upper muscle groups
- Mean 6MWT greater than or equal 300 meters and less than or equal to 450 meters
- Stable pulmonary and cardiac function: forced vital capacity (FVC) equal to or greater than 50% predicted and left ventricular ejection fraction (LVEF) greater than 50%
Exclusion Criteria:
- Previous treatment with SMT C1100 (BMN-195) at any time
- Treatment with gene therapy at any time
- Previous treatment with PRO045 or PRO053 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
- Participation in any other DMD interventional clinical study within 12 weeks prior to Week 1
- Major surgery within 3 months prior to Week 1
- Presence of other clinically significant illness
- Major change in physical therapy regimen within 3 months prior to Week 1
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02500381
Contacts
| Contact: Medical Information | +1 888 727 3782 | clinicaltrials@sarepta.com |
Hide Study Locations
Locations
| United States, Arizona | |
| Neuromuscular Research Center | Active, not recruiting |
| Phoenix, Arizona, United States, 85028 | |
| United States, California | |
| Children's Hospital Los Angeles | Active, not recruiting |
| Los Angeles, California, United States, 90027 | |
| David Geffen School of Medicine, UCLA | Active, not recruiting |
| Los Angeles, California, United States, 90095 | |
| UC Davis Medical Center | Active, not recruiting |
| Sacramento, California, United States, 95817 | |
| Rady Children's Hospital San Diego/ UCSD | Active, not recruiting |
| San Diego, California, United States, 92123 | |
| Stanford University School of Medicine/Medical Center | Active, not recruiting |
| Stanford, California, United States, 94305 | |
| United States, Connecticut | |
| Connecticut Children's Medical Center | Active, not recruiting |
| Hartford, Connecticut, United States, 06106 | |
| United States, Florida | |
| University of Florida | Active, not recruiting |
| Gainesville, Florida, United States, 32610 | |
| NW Florida Clinical Research Group, LLC | Active, not recruiting |
| Gulf Breeze, Florida, United States, 32561 | |
| Withdrawn | |
| Miami, Florida, United States | |
| United States, Georgia | |
| Center for Integrative Rare Disease Research (CIRDR) | Active, not recruiting |
| Atlanta, Georgia, United States, 30318 | |
| United States, Illinois | |
| Ann and Robert H. Lurie Children's Hospital of Chicago | Active, not recruiting |
| Chicago, Illinois, United States, 60611 | |
| United States, Iowa | |
| University of Iowa Children's Hospital | Active, not recruiting |
| Iowa City, Iowa, United States, 52242 | |
| United States, Kansas | |
| University of Kansas, Medical Center | Active, not recruiting |
| Kansas City, Kansas, United States, 66160 | |
| United States, Massachusetts | |
| Boston Children's Hospital | Active, not recruiting |
| Boston, Massachusetts, United States, 02115 | |
| United States, Missouri | |
| St. Louis Children's Hospital | Active, not recruiting |
| Saint Louis, Missouri, United States, 63110 | |
| United States, Nevada | |
| Las Vegas Clinic | Active, not recruiting |
| Las Vegas, Nevada, United States, 89145 | |
| United States, New York | |
| Not yet recruiting | |
| New York, New York, United States | |
| University of Rochester Clinical Research Center | Active, not recruiting |
| Rochester, New York, United States, 14642 | |
| United States, Ohio | |
| Cincinnati Children's Hospital Medical Center (CCHMC) | Active, not recruiting |
| Cincinnati, Ohio, United States, 45229 | |
| Nationwide Children's Hospital | Active, not recruiting |
| Columbus, Ohio, United States, 43205 | |
| United States, Oregon | |
| Shriners Hospital for Children | Active, not recruiting |
| Portland, Oregon, United States, 97239 | |
| United States, Pennsylvania | |
| Children's Hospital of Philadelphia | Active, not recruiting |
| Philadelphia, Pennsylvania, United States, 19104 | |
| Children's Hospital of Pittsburgh of UPMC | Active, not recruiting |
| Pittsburgh, Pennsylvania, United States, 15224 | |
| United States, Texas | |
| Children's Medical Center Dallas | Active, not recruiting |
| Dallas, Texas, United States, 75235 | |
| United States, Utah | |
| University of Utah | Active, not recruiting |
| Salt Lake City, Utah, United States, 84132 | |
| United States, Virginia | |
| Children's Hospital of the King's Daughters | Active, not recruiting |
| Norfolk, Virginia, United States, 23507 | |
| United States, Wisconsin | |
| Children's Hospital of Wisconsin | Active, not recruiting |
| Milwaukee, Wisconsin, United States, 53226 | |
| Australia, Victoria | |
| Royal Children's Hospital Melbourne | Recruiting |
| Parkville, Victoria, Australia, 3052 | |
| Contact: Jemima Mitchell +61399366157 jemima.mitchell@rch.org.au | |
| Principal Investigator: Monique Ryan | |
| Belgium | |
| Universitair Ziekenhuis Gent | Active, not recruiting |
| Ghent, Belgium, 9000 | |
| Universitair Ziekenhuis Leuven | Active, not recruiting |
| Leuven, Belgium, 3000 | |
| Canada, Alberta | |
| Alberta Childrens Hospital | Recruiting |
| Calgary, Alberta, Canada, T3B 6A8 | |
| Contact: Tiffany Haig (403) 955-3192 tiffany.haig@albertahealthservices.ca | |
| Principal Investigator: Jean Mah, MD | |
| Canada, Ontario | |
| London Health Sciences Centre | Active, not recruiting |
| London, Ontario, Canada, N6A 5W9 | |
| Czechia | |
| University Hospital Brno | Active, not recruiting |
| Brno, Czechia, 61300 | |
| Fakultni nemocnice v Motole | Active, not recruiting |
| Praha, Czechia, 15008 | |
| France | |
| Hôpital Des Enfants | Active, not recruiting |
| Toulouse, Haute-Garonne, France, 31059 | |
| Reference Centre for Neuromuscular Diseases | Active, not recruiting |
| Nantes, France, 44093 | |
| Hôpital Armand Trousseau | Active, not recruiting |
| Paris, France, 75012 | |
| Germany | |
| Universitätsklinikum Essen | Recruiting |
| Essen, Germany, 45122 | |
| Contact: Corinna Seifert +4920172385170 corinna.seifert@uk-essen.de | |
| Principal Investigator: Ulrike Schara, MD | |
| University Hospital Freiburg | Recruiting |
| Freiburg, Germany, 79106 | |
| Contact: Sabine Wider +4976127043440 sabine.wider@uniklinik-freiburg.de | |
| Principal Investigator: Janbernd Kirschner, MD | |
| LMU Klinikum der Universität München | Recruiting |
| Munich, Germany, 80337 | |
| Contact: Astrid Blaschek +4989440055110 astrid.blaschek@med.uni-muenchen.de | |
| Principal Investigator: Wolfgang Müller-Felber, MD | |
| Israel | |
| Schneider Children's Medical Center of Israel | Active, not recruiting |
| Petah Tikvah, Israel, 49102 | |
| Italy | |
| Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant' Anna | Active, not recruiting |
| Ferrara, Italy, 44124 | |
| Istituto Giannina Gaslini | Active, not recruiting |
| Genoa, Italy, 16147 | |
| Az Ospedaliera Universitaria Policlinico G Martino | Active, not recruiting |
| Messina, Italy, 98125 | |
| Policlinico Universitario A Gemelli | Recruiting |
| Rome, Italy, 00168 | |
| Contact: Mariarosaria Vizzino +390630158581 npi.clinicaltrials@rm.unicatt.it | |
| Principal Investigator: Eugenio Mercuri, MD | |
| Spain | |
| Hospital de La Santa Creu i Sant Pau | Recruiting |
| Barcelona, Spain, 08041 | |
| Contact: Nuria Vidal +34935537115 nvidalf@santpau.cat | |
| Principal Investigator: Jorge Diaz Manera, MD | |
| Hospital Sant Joan de Deu | Recruiting |
| Barcelona, Spain, 08950 | |
| Contact: Marina Garcia +34936009733 mgarciago@fsjd.org | |
| Principal Investigator: Andres Nascimento, MD | |
| Hospital Universitari i Politecnic La Fe de Valencia | Recruiting |
| Valencia, Spain | |
| Contact: Pilar Marti +34961244000 mapifres@gmail.com | |
| Principal Investigator: Juan Jesus Vilchez Padilla, MD | |
| Sweden | |
| Drottning Silvias Barn Och Ungdomssjukhus | Recruiting |
| Göteborg, Sweden, SE-41685 | |
| Contact: Anna-Lena Tulinius +46313436069 anna-lena.tulinius@vgregion.se | |
| Principal Investigator: Mar Tulinius, MD | |
| Not yet recruiting | |
| Stockholm, Sweden | |
| United Kingdom | |
| Leeds Teaching Hospitals NHS Trust | Recruiting |
| Leeds, United Kingdom, LS1 3EX | |
| Contact: Heather Rostron | |
| Principal Investigator: Ann-Marie Childs, MD | |
| Alder Hey Childrens Hospital | Recruiting |
| Liverpool, United Kingdom, L12 2AP | |
| Contact: Timothy Henderson +441512525164 Timothy.Henderson@alderhey.nhs.uk | |
| Principal Investigator: Stefan Spinty, MD | |
| Great Ormond Street Hospital (GOSH) | Recruiting |
| London, United Kingdom, WC1N 1EH | |
| Contact: Hinal Patel 020 7905 2639 ext 2639 hinal.patel@ucl.ac.uk | |
| Principal Investigator: Francesco Muntoni, MD | |
| Royal Victoria Infirmary | Recruiting |
| Newcastle upon Tyne, United Kingdom, NE1 4LP | |
| Contact: Valerie Corrall +4401912084569 valerie.corrall@ncl.ac.uk | |
| Principal Investigator: Volker Straub, MD | |
Sponsors and Collaborators
Sarepta Therapeutics
Investigators
| Study Director: | Medical Director | Sarepta Therapeutics, Inc. |
| Responsible Party: | Sarepta Therapeutics |
| ClinicalTrials.gov Identifier: | NCT02500381 History of Changes |
| Other Study ID Numbers: |
4045-301 |
| First Posted: | July 16, 2015 Key Record Dates |
| Last Update Posted: | December 3, 2018 |
| Last Verified: | November 2018 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes | |
| Studies a U.S. FDA-regulated Device Product: | No | |
Keywords provided by Sarepta Therapeutics:
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Duchenne muscular dystrophy Exon Skipping DMD Exon 53 |
Exon 45 Ambulatory Pediatric Duchenne |
Additional relevant MeSH terms:
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Muscular Dystrophies Muscular Dystrophy, Duchenne Muscular Disorders, Atrophic Muscular Diseases Musculoskeletal Diseases |
Neuromuscular Diseases Nervous System Diseases Genetic Diseases, Inborn Genetic Diseases, X-Linked |