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Trial record 5 of 29 for:    skipping | "muscular dystrophy, duchenne and becker types"

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

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ClinicalTrials.gov Identifier: NCT02310906
Recruitment Status : Active, not recruiting
First Posted : December 8, 2014
Last Update Posted : November 26, 2018
Sponsor:
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

Brief Summary:
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 or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: Placebo Drug: SRP-4053 Phase 1 Phase 2

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 and an untreated group of 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 group will not undergo biopsies and will follow an abbreviated schedule of study assessments.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 39 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Masking Description: Part 1 is double-blind and randomized; Part 2 is open-label.
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
Actual Study Start Date : January 13, 2015
Actual Primary Completion Date : October 18, 2018
Estimated Study Completion Date : April 29, 2019


Arm Intervention/treatment
Experimental: Part 1: SRP-4053
Patients will receive SRP-4053 intravenous (IV) infusions, weekly, at escalating dose levels as follows: Weeks 1-2, 4 mg/kg/week; Weeks 3-4, 10 mg/kg/week; Weeks 5-6, 20 mg/kg/week; Weeks 7-12, 30 mg/kg/week. Dosing will be interrupted or halted if specific predefined stopping criteria are met or if warranted at the discretion of the Sponsor or Investigator.
Drug: SRP-4053
SRP-4053 solution for IV infusion

Placebo Comparator: Part 1: Placebo
Patients will receive SRP-4053 placebo-matching IV infusions, weekly, for 12 weeks. Dosing will be interrupted or halted if specific predefined stopping criteria are met or if warranted at the discretion of the Sponsor or Investigator.
Drug: Placebo
SRP-4053 placebo-matching solution for IV infusion

Experimental: Part 2: SRP-4053
All eligible patients from Part 1, as well as new patients, will receive SRP-4053 30 mg/kg/week IV infusions, weekly, for up to 168 weeks.
Drug: SRP-4053
SRP-4053 solution for IV infusion

No Intervention: Part 2: Untreated Group
Patients with DMD who have a genotypically confirmed deletion of exon(s) not amenable to treatment by exon 53 skipping, but who otherwise meet the same eligibility criteria as treated patients newly recruited to Part 2, will undergo the same study assessments as treated Patients (except for pharmacokinetic [PK] sampling and muscle biopsies), but at a reduced schedule through Week 144.



Primary Outcome Measures :
  1. Part 1: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: approximately 12 weeks ]
  2. Part 2: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 144 [ Time Frame: Baseline and Week 144 ]
  3. Part 2: Change from Baseline in Dystrophin Protein Levels Determined by Western Blot at Week 48 [ Time Frame: Baseline to Week 48 ]

Secondary Outcome Measures :
  1. Part 1: Maximum Plasma Concentration (Cmax) [ Time Frame: Pre-dose, 5 to 10 minutes and 1 to 24 hours post-dose at Weeks 1, 3, 5 and 7 ]
  2. Part 1: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: Pre-dose, 5 to 10 minutes and 1 to 24 hours post-dose at Weeks 1, 3, 5 and 7 ]
  3. Part 1: Area Under the Plasma Concentration-time Curve (AUC) [ Time Frame: Pre-dose, 5 to 10 minutes and 1 to 24 hours post-dose at Weeks 1, 3, 5 and 7 ]
  4. Part 1: Apparent Volume of Distribution at Steady State (Vss) [ Time Frame: Pre-dose, 5 to 10 minutes and 1 to 24 hours post-dose at Weeks 1, 3, 5 and 7 ]
  5. Part 1: Elimination Half-life (t½) [ Time Frame: Pre-dose, 5 to 10 minutes and 1 to 24 hours post-dose at Weeks 1, 3, 5 and 7 ]
  6. Part 1: Total Clearance (CL) [ Time Frame: Pre-dose, 5 to 10 minutes and 1 to 24 hours post-dose at Weeks 1, 3, 5 and 7 ]
  7. Part 1: Mean Residence Time (MRT) [ Time Frame: Pre-dose, 5 to 10 minutes and 1 to 24 hours post-dose at Weeks 1, 3, 5 and 7 ]
  8. Part 1: Urinary Clearance (CLR) [ Time Frame: Day 1, 0-4 hours, 4-8 hours, 8-12 hours, and 12-24 after initiation of dosing ]
  9. Part 2: Change from Baseline in Forced Vital Capacity Percent Predicted (FVC%p) through Week144 [ Time Frame: Baseline through Week 144 ]
    The FVC is the maximal volume of air that can be exhaled from full inhalation by exhaling as forcefully and rapidly as possible. Patients will be assessed with delayed in the loss of respiratory function.

  10. Part 2: Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 [ Time Frame: Baseline and Week 48 ]
  11. Part 2: Exon 53 Skipping Determined by Measurement and Sequence Verification of Exon 53 Skipped Messenger Ribonucleic Acid (RNA) [ Time Frame: Baseline and Week 48 ]


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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.


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
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02116
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: Medical Director Sarepta Therapeutics, Inc.

Responsible Party: Sarepta Therapeutics
ClinicalTrials.gov Identifier: NCT02310906     History of Changes
Other Study ID Numbers: 4053-101
First Posted: December 8, 2014    Key Record Dates
Last Update Posted: November 26, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sarepta Therapeutics:
Duchenne muscular dystrophy
Exon Skipping
DMD
Exon 53
Ambulatory
Pediatric

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