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Systemic Gene Delivery Clinical Trial for Duchenne Muscular Dystrophy (DMD)

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. Identifier: NCT03375164
Recruitment Status : Active, not recruiting
First Posted : December 15, 2017
Last Update Posted : November 10, 2020
Information provided by (Responsible Party):
Sarepta Therapeutics, Inc.

Brief Summary:
The proposed clinical trial is a single-dose controlled trial using rAAVrh74.MHCK7.micro-dystrophin for DMD patients. Cohort A will include six patients ages 3 months to 3 years, and Cohort B will include six patients ages 4 to 7 years old. All patients will receive intravenous SRP-9001.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Genetic: SRP-9001 Phase 1 Phase 2

Detailed Description:
In this study, the gene will be infused via peripheral arm vein so that it can reach all the muscles in the body. Six DMD patients ages 3 months to 3 years in Cohort A, and six DMD patients ages 4 years to age 7 years in Cohort B, will be enrolled. All patients will receive SRP-9001. Patients will have infusions over 1-2 hours in the Pediatric Intensive Care Unit (PICU) at Nationwide Children's Hospital. Before the gene therapy a muscle biopsy will be done at the screening visit. Patients will have a second muscle biopsy to see if the gene allowed for replacement of the missing dystrophin protein at 90 days post-delivery. After the gene transfer, patients will be carefully monitored, for 5 years to evaluate any side effects of the treatment.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Systemic Gene Delivery Phase I/IIa Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MHCK7. Micro-dystrophin (microDys-IV-001)
Actual Study Start Date : January 4, 2018
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2023

Arm Intervention/treatment
Experimental: Cohort A
Patients between 3 months to 3 years of age, will receive intravenous SRP-9001.
Genetic: SRP-9001
Single IV infusion of SRP-9001.

Experimental: Cohort B
Patients between 4 to 7 years of age, will receive intravenous SRP-9001.
Genetic: SRP-9001
Single IV infusion of SRP-9001.

Primary Outcome Measures :
  1. Safety Based on Number of Participants with Adverse Events. [ Time Frame: From baseline up to 5 years ]
    AEs will be monitored and scored for severity and relatedness to the study article.

Secondary Outcome Measures :
  1. Cohort A : Gross Motor Subtest Scaled (Bayley-III) score [ Time Frame: Screening, Day 30-3 Years ]
    Gross Motor Scaled Score measures motor development. The Bayley-III Gross Motor Subtest will be scored for Cohort A on every follow up visit starting at Day 30 through 3 years. Any patient that is 43-47 months of age, inclusive, at time of screening will have the scaled score calculated compared to normative data for 42 month old children. The Bayley-III provides normative data for children 1-42 months of age.

  2. Cohort B: Physical Therapy Assessments The 100 Meter Timed Test (100m) [ Time Frame: Screening, Day 30-5 Years ]
    The 100m will be the primary motor outcome for Cohort B.

  3. Micro-dystrophin Gene Expression Quantification by Immunofluorescence [ Time Frame: Screening and Day 90 ]
    Micro-dystrophin gene expression levels will be quantified by immunofluorescence and compared in pre and post muscle biopsies.

  4. Micro-dystrophin Gene Expression Quantification by Western Blot [ Time Frame: Screening and Day 90 ]
    Micro-dystrophin gene expression levels will be quantified by western blot analysis and compared in pre and post muscle biopsies.

Other Outcome Measures:
  1. Physical Therapy Assessments North Star Ambulatory Assessment (NSAA) [ Time Frame: Screening, Day 30-5 Years ]
    The North Star Ambulatory Assessment (NSAA) will be an exploratory outcome initiated for Cohort A as soon as the child is four years of age and for cohort B. The NSAA measures the quality of ambulation in young boys with Duchenne Muscular Dystrophy.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   3 Months to 7 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Cohort A patients: 3 months to 3 years of age, inclusive
  • Cohort B patients: 4 to 7 years of age, inclusive
  • Molecular characterization of the DMD gene with frameshift (deletion or duplication), or premature stop codon mutation between exons 18 to 58
  • CK elevation >1000 U/L and
  • Cohort A patients: below average on the Bayley-III motor assessment for gross motor defined as a scaled score of ≤9.
  • Cohort B patients: below average on the 100 Meter Timed Test defined as ≤ 80% predicted.
  • Males of any ethnic group
  • Ability to cooperate with motor assessment testing.
  • Cohort A patients: No previous treatment with corticosteroids.
  • Cohort B patients: Stable dose equivalent of oral corticosteroids for at least 12 weeks prior to screening and the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the first year of the study .

Exclusion Criteria:

  • Active viral infection based on clinical observations.
  • Signs of cardiomyopathy, including echocardiogram with ejection fraction below 40%.
  • Serological evidence of HIV infection, or Hepatitis B or C infection.
  • Diagnosis of (or ongoing treatment for) an autoimmune disease.
  • Abnormal laboratory values considered clinically significant.
  • Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer.
  • Patients with rAAVrh74 or AAV8 antibody titers > 1:400 as determined by enzyme-linked immunosorbent assay (ELISA) immunoassay.
  • Medical condition or extenuating circumstance that, in the opinion of the investigator, might compromise the patient's ability to comply with the protocol required testing or procedures or compromise the patient's wellbeing, safety, or clinical interpretability.
  • Severe infection (e.g., pneumonia, pyelonephritis, or meningitis) within 4 weeks before gene transfer visit (enrollment may be postponed).
  • Received any investigational medication (other than corticosteroids) or exon skipping medications (including EXONDYS 51), experimental or otherwise, in the last 6 months prior to screening for this study.
  • Received any type of gene therapy, cell based therapy (e.g. stem cell transplantation), or CRISPR/Cas9.
  • Family does not want to disclose patient's study participation with primary care physician and other medical providers.

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 identifier (NCT number): NCT03375164

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United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Sponsors and Collaborators
Sarepta Therapeutics, Inc.
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Study Director: Medical Director Sarepta Therapeutics, Inc.
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Sarepta Therapeutics, Inc. Identifier: NCT03375164    
Other Study ID Numbers: SRP-9001-101
IRB17-00512 ( Other Identifier: Nationwide Children's Hospital )
First Posted: December 15, 2017    Key Record Dates
Last Update Posted: November 10, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sarepta Therapeutics, Inc.:
gene therapy
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked