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Phase I/II Study of SRP-4053 in DMD Patients

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02310906
First Posted: December 8, 2014
Last Update Posted: October 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Institut de Myologie, France
Consultants for Research in Imaging and Spectroscopy
Great Ormond Street Hospital for Children NHS Foundation Trust
Catholic University of the Sacred Heart
Royal Holloway University
SYSNAV
University College, London
University of Newcastle Upon-Tyne
Information provided by (Responsible Party):
Sarepta Therapeutics
  Purpose
This is a first-in-human, multiple-dose 2-part study to assess the safety, tolerability, efficacy, and pharmacokinetics of SRP-4053 in Duchenne muscular dystrophy (DMD) patients with deletions amenable to exon 53 skipping.

Condition Intervention Phase
Duchenne Muscular Dystrophy Drug: Placebo Drug: SRP-4053 Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 2-Part, Randomized, Double-Blind, Placebo-Controlled, Dose-Titration, Safety, Tolerability, and Pharmacokinetics Study (Part 1) Followed by an Open-Label Efficacy and Safety Evaluation (Part 2) of SRP-4053 in Patients With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping

Resource links provided by NLM:


Further study details as provided by Sarepta Therapeutics:

Primary Outcome Measures:
  • Incidence of Adverse Events [ Time Frame: approximately 12 weeks (Part 1) ]
  • Incidence of clinical laboratory abnormalities (hematology, chemistry, coagulation, urinalysis) [ Time Frame: approximately 12 weeks (Part 1) ]
  • Incidence of abnormalities in vital signs and physical examinations [ Time Frame: approximately 12 weeks (Part 1) ]
  • Incidence of abnormalities on ECGs and ECHOs [ Time Frame: approximately 12 weeks (Part 1) ]
  • Change in 6-Minute Walk Test (6MWT) from baseline [ Time Frame: Baseline to Week 144 (Part 2) ]
  • Dystrophin protein levels determined by western blot [ Time Frame: Baseline to Week 48 (Part 2) ]

Secondary Outcome Measures:
  • Drug concentration in plasma [ Time Frame: Approximately 12 weeks (Part 1) ]
  • Pulmonary function tests [ Time Frame: Baseline to Week 144 (Part 2) ]
    Maximum expiratory pressure (MEP)%, maximum inspiratory pressure (MIP)%

  • Percentage of dystrophin-positive fibers determined by IHC [ Time Frame: Baseline to Week 48 (Part 2) ]
  • Exon 53 skipping [ Time Frame: Baseline to Week 48 (Part 2) ]

Other Outcome Measures:
  • Incidence of Adverse Events [ Time Frame: 144 weeks (Part 2) ]
  • Incidence of clinical laboratory abnormalities (hematology, chemistry, coagulation, urinalysis) [ Time Frame: 144 weeks (Part 2) ]
  • Incidence of abnormalities in vital signs and physical examinations [ Time Frame: 144 weeks (Part 2) ]
  • Incidence of abnormalities on ECGs and ECHOs [ Time Frame: 144 weeks (Part 2) ]
  • Immunogenicity [ Time Frame: 144 weeks (Part 2) ]

Enrollment: 39
Study Start Date: December 2014
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1, Part 2 SRP-4053
Approximately 8 genotypically confirmed DMD patients amenable to exon 53 skipping
Drug: SRP-4053
Placebo Comparator: Part 1 Placebo, Part 2 SRP-4053
Approximately 4 genotypically confirmed DMD patients amenable to exon 53 skipping
Drug: Placebo Drug: SRP-4053
Experimental: Part 2 SRP-4053
Approximately 24 genotypically confirmed DMD patients amenable to exon 53 skipping
Drug: SRP-4053
No Intervention: Part 2 Untreated Control
Up to 24 genotypically confirmed DMD patients with deletions not amenable to exon 53 skipping

Detailed Description:

Part 1: Randomized, placebo-controlled dose-titration to assess safety, tolerability and pharmacokinetics of 4 dose levels of SRP-4053 in genotypically-confirmed DMD patients with deletions amenable to exon 53 skipping.

Part 2: Open-label evaluation of SRP-4053 in patients from Part 1, along with newly enrolled DMD patients with deletions amenable to exon 53 skipping, compared to untreated control DMD patients with deletions not amenable to exon 53 skipping.

Safety, including adverse event monitoring and routine laboratory assessments, will be followed on an ongoing basis for all patients.

Clinical efficacy, including functional tests such as the six-minute walk test (6MWT), will be assessed at regularly scheduled study visits. Patients in the treated groups will undergo one baseline and one follow-up muscle biopsy. Patients in the untreated control group will not undergo biopsies and will follow an abbreviated schedule of study assessments.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 15 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosed with DMD, genotypically confirmed.
  • Intact right and left biceps muscles or an alternative upper arm muscle group.
  • Stable pulmonary and cardiac function.
  • Minimum performance on 6MWT, North Star Ambulatory Assessment, and rise (Gowers) test as specified in the study protocol.
  • On a stable dose of corticosteroids for at least 6 months.

Exclusion Criteria:

  • Previous treatment with the experimental agents BMN-195 (SMT C1100) or PRO053.
  • Current or previous treatment with any other experimental treatments within 12 weeks prior to study entry.
  • Major surgery within the last 3 months.
  • Presence of other clinically significant illness.
  • Major change in physical therapy regime within the last 3 months.

Other inclusion and exclusion criteria may apply.

  Contacts and Locations
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): NCT02310906


Locations
France
Institute de Myologie
Paris, France, 75013
Italy
Policlinico Universitario A Gemelli
Rome, Italy, 00168
United Kingdom
Great Ormond Street Hospital for Children NHS Foundation Trust
London, United Kingdom, WC1N 3JH
Newcastle University Hospital
Newcastle, United Kingdom
Sponsors and Collaborators
Sarepta Therapeutics
Institut de Myologie, France
Consultants for Research in Imaging and Spectroscopy
Great Ormond Street Hospital for Children NHS Foundation Trust
Catholic University of the Sacred Heart
Royal Holloway University
SYSNAV
University College, London
University of Newcastle Upon-Tyne
Investigators
Study Director: Jon Lu, MD Sarepta Therapeutics
Study Director: Catherine Stehman-Breen, MD Sarepta Therapeutics
  More Information

Responsible Party: Sarepta Therapeutics
ClinicalTrials.gov Identifier: NCT02310906     History of Changes
Other Study ID Numbers: 4053-101
First Submitted: December 3, 2014
First Posted: December 8, 2014
Last Update Posted: October 3, 2017
Last Verified: October 2017

Keywords provided by Sarepta Therapeutics:
Duchenne muscular dystrophy
Exon Skipping

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked