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

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.
ClinicalTrials.gov Identifier: NCT02310906
Recruitment Status : Active, not recruiting
First Posted : December 8, 2014
Last Update Posted : March 15, 2019
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

Tracking Information
First Submitted Date  ICMJE December 3, 2014
First Posted Date  ICMJE December 8, 2014
Last Update Posted Date March 15, 2019
Actual Study Start Date  ICMJE January 13, 2015
Estimated Primary Completion Date March 29, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 16, 2018)
  • Part 1: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: approximately 12 weeks ]
  • 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 ]
  • Part 2: Change from Baseline in Dystrophin Protein Levels Determined by Western Blot at Week 48 [ Time Frame: Baseline to Week 48 ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 5, 2014)
  • Incidence of Adverse Events [ Time Frame: approximately 12 weeks (Part 1) ]
  • Change in 6-Minute Walk Test (6MWT) from baseline [ Time Frame: 48 weeks (Part 2) ]
  • Percentage of dystrophin-positive fibers [ Time Frame: 48 weeks (Part 2) ]
Change History Complete list of historical versions of study NCT02310906 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2018)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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.
  • Part 2: Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 [ Time Frame: Baseline and Week 48 ]
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 5, 2014)
  • Drug concentration in plasma [ Time Frame: Approximately 12 weeks (Part 1) ]
  • Maximum inspiratory pressure (MIP) % predicted, maximum expiratory pressure (MEP) % predicted [ Time Frame: 48 weeks (Part 2) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: December 5, 2014)
Incidence of Adverse Events [ Time Frame: 48 weeks (Part 2) ]
 
Descriptive Information
Brief Title  ICMJE Phase I/II Study of SRP-4053 in DMD Patients
Official Title  ICMJE 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
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE Duchenne Muscular Dystrophy
Intervention  ICMJE
  • Drug: Placebo
    SRP-4053 placebo-matching solution for IV infusion
  • Drug: SRP-4053
    SRP-4053 solution for IV infusion
Study Arms  ICMJE
  • 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.
    Intervention: Drug: SRP-4053
  • 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.
    Intervention: Drug: Placebo
  • 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.
    Intervention: Drug: SRP-4053
  • 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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 25, 2016)
39
Original Estimated Enrollment  ICMJE
 (submitted: December 5, 2014)
48
Estimated Study Completion Date  ICMJE March 29, 2019
Estimated Primary Completion Date March 29, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 6 Years to 15 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Italy,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02310906
Other Study ID Numbers  ICMJE 4053-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sarepta Therapeutics
Study Sponsor  ICMJE Sarepta Therapeutics
Collaborators  ICMJE
  • 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  ICMJE
Study Director: Medical Director Sarepta Therapeutics, Inc.
PRS Account Sarepta Therapeutics
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP