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 : April 18, 2018
|Condition or disease||Intervention/treatment||Phase|
|Duchenne Muscular Dystrophy||Drug: Placebo Drug: SRP-4053||Phase 1 Phase 2|
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|
|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.|
|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|
|Study Start Date :||December 2014|
|Estimated Primary Completion Date :||March 2019|
|Estimated Study Completion Date :||June 2019|
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.
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.
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.
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.
- 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 ]
- 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 ]
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
|United States, Massachusetts|
|Boston Children's Hospital|
|Boston, Massachusetts, United States, 02116|
|Institute de Myologie|
|Paris, France, 75013|
|Policlinico Universitario A Gemelli|
|Rome, Italy, 00168|
|Great Ormond Street Hospital for Children NHS Foundation Trust|
|London, United Kingdom, WC1N 3JH|
|Newcastle University Hospital|
|Newcastle, United Kingdom|
|Study Director:||Jon Lu, MD PhD||Sarepta Therapeutics|
|Study Director:||Chris Mix, MD||Sarepta Therapeutics|