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出境医 / 临床实验 / Study for Dose Determination of SRP-5051, Then Dose Expansion in Patients With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment (MOMENTUM)

Study for Dose Determination of SRP-5051, Then Dose Expansion in Patients With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment (MOMENTUM)

Study Description
Brief Summary:
This study will be comprised of 2 parts: 1) Part A (Multiple Ascending Dose [MAD]) will be conducted to evaluate the safety and tolerability of SRP-5051 at multiple ascending dose levels to determine the maximum tolerated dose (MTD), and 2) Part B (Dose Expansion) will be conducted to evaluate SRP-5051 administered at the MTD determined in Part A or, if applicable, at a second dose introduced in Part B. Patients enrolling in Part B will be those who completed Part A as well as additional expansion cohort patients who will enroll at the beginning of Part B.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: SRP-5051 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Two-Part, Multiple-Ascending-Dose Study of SRP-5051 for Dose Determination, Then Dose Expansion, in Patients With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment
Actual Study Start Date : June 26, 2019
Estimated Primary Completion Date : May 31, 2022
Estimated Study Completion Date : May 31, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Part A: SRP-5051
Patients will be sequentially assigned to receive 1 of the 5 escalating dose levels of SRP-5051, monthly, via intravenous (IV) infusion for at least 12 weeks during Part A. Once the maximum tolerated dose (MTD) has been determined in Part A, all patients who have completed Part A will transition to Part B.
 Drug: SRP-5051
SRP-5051 injection, for IV use
Experimental: Part B: SRP-5051
Patients will receive SRP-5051 at the MTD determined in Part A, or if applicable, at a second dose introduced in Part B, monthly, via IV infusion, for 24 weeks. This includes the patients who roll over from Part A, as well as expansion cohort patients who will enroll in the study at the beginning of Part B.
 Drug: SRP-5051
SRP-5051 injection, for IV use
Outcome Measures
Primary Outcome Measures :
  1. Part A: Incidence of Adverse Events (AEs) [ Time Frame: Part A: approximately 68 weeks ]
    Incidence of adverse events includes clinically significant laboratory abnormalities.

  2. Part B: Change From Baseline in Dystrophin Protein Level [ Time Frame: Baseline, Week 12 or Week 24 ]

Secondary Outcome Measures :
  1. Part A: Pharmacokinetics (PK): Plasma Concentration of SRP-5051 [ Time Frame: Pre-dose and at multiple time points (up to 32 hours) after end of infusion ]
  2. Part A: PK: Urine Concentration of SRP-5051 [ Time Frame: Pre-dose and at multiple time periods (up to 48 hours) after end of infusion ]
  3. Part B: Change From Baseline in Exon-Skipping Levels [ Time Frame: Baseline, Week 12 or Week 24 ]
  4. Part B: Incidence of Adverse Events (AEs) [ Time Frame: Part B: approximately 44 weeks ]
    Incidence of adverse events includes clinically significant laboratory abnormalities.

  5. Part B: Change From Baseline in Forced Vital Capacity (FVC) (percent predicted) [ Time Frame: Baseline, Week 12 or Week 24 ]
  6. Part B: Change From Baseline in the North Star Ambulatory Assessment (NSAA) [ Time Frame: Baseline, Week 12 or Week 24 ]
  7. Part B: Change From Baseline in the Performance of Upper Limb (PUL) Scores [ Time Frame: Baseline, Week 12 or Week 24 ]
  8. Part B: Change From Baseline in the Brooke Upper Extremity Scale score (Brooke score) [ Time Frame: Baseline, Week 12 or Week 24 ]
  9. Part B: PK: Plasma Concentration of SRP-5051 [ Time Frame: Part B predose and at multiple timepoints (up to 24 hours) after end of infusion ]

Eligibility Criteria
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Ages Eligible for Study:   4 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has a genetic diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51-skipping treatment.
  • Has been on a stable dose of oral corticosteroids for at least 12 weeks prior to study drug administration, or has not received corticosteroids for at least 12 weeks prior to study drug administration.
  • Part A age group (ages 7 to 21)
  • Part B age group (ages 4 to 21)

Exclusion Criteria:

  • Has a left ventricular ejection fraction (LVEF) less than (<) 40.0 percent (%) based on an echocardiogram (ECHO) performed within 12 weeks prior to Screening or at the Screening visit.
  • Has a FVC < 40.0% of predicted value within 12 weeks prior to Screening or at Screening.
  • Initiation or change of dosing (except for modifications to accommodate changes in weight or changes in standard of care) within 12 weeks prior to Screening for any of the following: angiotensin-converting enzyme inhibitors, angiotensin receptor-blocking agents, β-blockers, or potassium.
  • Initiation or change of dosing within 12 weeks prior to Screening for over-the-counter preparations, such as herbal/nonherbal supplements, vitamins, minerals, and homeopathic preparations.
  • Treatment with any exon 51-skipping therapy within 12 weeks prior to Screening, or with any experimental gene therapy for the treatment of DMD at any time.

Other inclusion/exclusion criteria apply

Contacts and Locations

Locations
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United States, Florida
Northwest Florida Clinical Research Group, LLC
Gulf Breeze, Florida, United States, 32561
United States, Georgia
Rare Disease Research, LLC
Atlanta, Georgia, United States, 30318
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52242
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Austin Neuromuscular Center
Austin, Texas, United States, 78756
Belgium
Universitair Ziekenhuis Gent
Gent, Belgium, 9000
Canada, Ontario
Children's Hospital - London Health Sciences Centre (LHSC)
London, Ontario, Canada, N6A 5W9
Spain
Hospital Sant Joan de Déu. U.B.
Barcelona, Spain, 08950
Hospital Universitari I Politecnic La Fe de Valencia
Valencia, Spain, 46026
United Kingdom
Alder Hey Children's NHS Foundation Trust
Liverpool, United Kingdom, L12 2AP
Sponsors and Collaborators
Sarepta Therapeutics, Inc.
Investigators
Layout table for investigator information
Study Director: Medical Director Sarepta Therapeutics, Inc.
Tracking Information
First Submitted Date  ICMJE June 27, 2019
First Posted Date  ICMJE July 1, 2019
Last Update Posted Date May 4, 2021
Actual Study Start Date  ICMJE June 26, 2019
Estimated Primary Completion Date May 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 5, 2021)
  • Part A: Incidence of Adverse Events (AEs) [ Time Frame: Part A: approximately 68 weeks ]
    Incidence of adverse events includes clinically significant laboratory abnormalities.
  • Part B: Change From Baseline in Dystrophin Protein Level [ Time Frame: Baseline, Week 12 or Week 24 ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
  • Part A: Incidence of Adverse Events (AEs) [ Time Frame: From signing of informed consent until 28 days after last dose of study drug administered (up to 60 weeks) ]
    Incidence of adverse events includes clinically significant laboratory abnormalities.
  • Part B: Change From Baseline Biopsy in Exon-Skipping Levels [ Time Frame: Baseline, Part B Week 24 ]
  • Part B: Change From Baseline Biopsy in Dystrophin Protein Production Levels [ Time Frame: Baseline, Part B Week 24 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 5, 2021)
  • Part A: Pharmacokinetics (PK): Plasma Concentration of SRP-5051 [ Time Frame: Pre-dose and at multiple time points (up to 32 hours) after end of infusion ]
  • Part A: PK: Urine Concentration of SRP-5051 [ Time Frame: Pre-dose and at multiple time periods (up to 48 hours) after end of infusion ]
  • Part B: Change From Baseline in Exon-Skipping Levels [ Time Frame: Baseline, Week 12 or Week 24 ]
  • Part B: Incidence of Adverse Events (AEs) [ Time Frame: Part B: approximately 44 weeks ]
    Incidence of adverse events includes clinically significant laboratory abnormalities.
  • Part B: Change From Baseline in Forced Vital Capacity (FVC) (percent predicted) [ Time Frame: Baseline, Week 12 or Week 24 ]
  • Part B: Change From Baseline in the North Star Ambulatory Assessment (NSAA) [ Time Frame: Baseline, Week 12 or Week 24 ]
  • Part B: Change From Baseline in the Performance of Upper Limb (PUL) Scores [ Time Frame: Baseline, Week 12 or Week 24 ]
  • Part B: Change From Baseline in the Brooke Upper Extremity Scale score (Brooke score) [ Time Frame: Baseline, Week 12 or Week 24 ]
  • Part B: PK: Plasma Concentration of SRP-5051 [ Time Frame: Part B predose and at multiple timepoints (up to 24 hours) after end of infusion ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
  • Part A: Pharmacokinetic (PK) Plasma Concentration of SRP-5051 [ Time Frame: Predose and at multiple timepoints (up to 24 hours) after end of infusion ]
  • Part B: Incidence of Adverse Events (AEs) [ Time Frame: Up to 28 weeks in Part B ]
    Incidence of adverse events includes clinically significant laboratory abnormalities.
  • Part B: Change From Baseline in Forced Vital Capacity (FVC) (percent predicted) [ Time Frame: Baseline, Part B Week 24 ]
  • Part B: Change From Baseline in the North Star Ambulatory Assessment (NSAA) [ Time Frame: Baseline, Part B Week 24 ]
  • Part B: Change From Baseline in the Performance of Upper Limb (PUL) Scores [ Time Frame: Baseline, Part B Week 24 ]
  • Part B: Change From Baseline in the Brooke Upper Extremity Scale score (Brooke score) [ Time Frame: Baseline, Part B Week 24 ]
  • Part B: PK Plasma Concentration of SRP-5051 [ Time Frame: Part B predose and at multiple timepoints (up to 12 hours) after end of infusion ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study for Dose Determination of SRP-5051, Then Dose Expansion in Patients With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment
Official Title  ICMJE A Phase 2, Two-Part, Multiple-Ascending-Dose Study of SRP-5051 for Dose Determination, Then Dose Expansion, in Patients With Duchenne Muscular Dystrophy Amenable to Exon 51-Skipping Treatment
Brief Summary This study will be comprised of 2 parts: 1) Part A (Multiple Ascending Dose [MAD]) will be conducted to evaluate the safety and tolerability of SRP-5051 at multiple ascending dose levels to determine the maximum tolerated dose (MTD), and 2) Part B (Dose Expansion) will be conducted to evaluate SRP-5051 administered at the MTD determined in Part A or, if applicable, at a second dose introduced in Part B. Patients enrolling in Part B will be those who completed Part A as well as additional expansion cohort patients who will enroll at the beginning of Part B.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Duchenne Muscular Dystrophy
Intervention  ICMJE Drug: SRP-5051
SRP-5051 injection, for IV use
Study Arms  ICMJE
  • Experimental: Part A: SRP-5051
    Patients will be sequentially assigned to receive 1 of the 5 escalating dose levels of SRP-5051, monthly, via intravenous (IV) infusion for at least 12 weeks during Part A. Once the maximum tolerated dose (MTD) has been determined in Part A, all patients who have completed Part A will transition to Part B.
    Intervention: Drug: SRP-5051
  • Experimental: Part B: SRP-5051
    Patients will receive SRP-5051 at the MTD determined in Part A, or if applicable, at a second dose introduced in Part B, monthly, via IV infusion, for 24 weeks. This includes the patients who roll over from Part A, as well as expansion cohort patients who will enroll in the study at the beginning of Part B.
    Intervention: Drug: SRP-5051
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
Estimated Enrollment  ICMJE
 (submitted: January 5, 2021) 		70
Original Estimated Enrollment  ICMJE
 (submitted: June 27, 2019) 		24
Estimated Study Completion Date  ICMJE May 31, 2022
Estimated Primary Completion Date May 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has a genetic diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51-skipping treatment.
  • Has been on a stable dose of oral corticosteroids for at least 12 weeks prior to study drug administration, or has not received corticosteroids for at least 12 weeks prior to study drug administration.
  • Part A age group (ages 7 to 21)
  • Part B age group (ages 4 to 21)

Exclusion Criteria:

  • Has a left ventricular ejection fraction (LVEF) less than (<) 40.0 percent (%) based on an echocardiogram (ECHO) performed within 12 weeks prior to Screening or at the Screening visit.
  • Has a FVC < 40.0% of predicted value within 12 weeks prior to Screening or at Screening.
  • Initiation or change of dosing (except for modifications to accommodate changes in weight or changes in standard of care) within 12 weeks prior to Screening for any of the following: angiotensin-converting enzyme inhibitors, angiotensin receptor-blocking agents, β-blockers, or potassium.
  • Initiation or change of dosing within 12 weeks prior to Screening for over-the-counter preparations, such as herbal/nonherbal supplements, vitamins, minerals, and homeopathic preparations.
  • Treatment with any exon 51-skipping therapy within 12 weeks prior to Screening, or with any experimental gene therapy for the treatment of DMD at any time.

Other inclusion/exclusion criteria apply
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 4 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04004065
Other Study ID Numbers  ICMJE 5051-201
2019-000601-77 ( EudraCT Number )
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, Inc.
Study Sponsor  ICMJE Sarepta Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Sarepta Therapeutics, Inc.
PRS Account Sarepta Therapeutics, Inc.
Verification Date April 2021

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

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