Duchenne Muscular Dystrophy Clinical Trial
Official title:
Phase I/IIa Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.GALGT2
Verified date | September 2023 |
Source | Nationwide Children's Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The proposed clinical trial study of rAAVrh74.MCK.GALGT2 for duchenne muscular dystrophy (DMD) patients. There will be a modified intravascular limb infusion (ILI) procedure that will be used to sequentially deliver vector to each whole lower limb of DMD subjects via a major lower limb artery.
Status | Active, not recruiting |
Enrollment | 2 |
Est. completion date | October 2023 |
Est. primary completion date | November 4, 2020 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | 4 Years and older |
Eligibility | Inclusion Criteria - Ambulant patients age 4 years or older - Confirmed mutations in the DMD gene using a clinical accepted technique that completely defines the mutation 1,2 - • Measurably impaired muscle function (defined as less than 80% of the predicted value for 100 MWT), but with sufficient muscle preservation to ensure assessment of muscle transfection based on clinical evaluation by the PI and expert colleagues. This degree of preservation will include: - Ability to extend the knee fully against gravity - Preserved ambulation with ability to walk = 350 meters during the 6MWT - A magnetic resonance image of the quadriceps showing preservation of sufficient muscle mass to permit transfection - Males of any ethnic group will be eligible - Ability to cooperate with muscle testing - Stable daily dose of corticosteroid therapy (including either prednisone, prednisolone, deflazacort or their generic forms) for 12 weeks prior to gene transfer Exclusion Criteria - Active viral infection based on clinical observations - The presence of a DMD mutation without weakness or loss of function - Subject is amenable to or is currently being treated with eteplirsen - Symptoms or signs of cardiomyopathy, including: - Dyspnea on exertion, pedal edema, shortness of breath upon lying flat, or rales at the base of the lungs - 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 - Persistent leukopenia or leukocytosis (WBC = 3.5 K/µL or = 20.0 K/µL) or an absolute neutrophil count < 1.5K/µL - Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer - Subjects with rAAVrh74 binding antibody titers = 1:50 as determined by ELISA immunoassay - Presence of circulating anti-Sda antibodies as determined by study approved laboratory - Abnormal laboratory values in the clinically significant range, based upon normal values in the Nationwide Children's Hospital Laboratory |
Country | Name | City | State |
---|---|---|---|
United States | Nationwide Children's Hospital | Columbus | Ohio |
Lead Sponsor | Collaborator |
---|---|
Kevin Flanigan |
United States,
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* Note: There are 35 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Number of Meters Walked During the 6 Minute Walk Test | Day 90 (Cohort 2) and Day 120 (Cohort 1) and Day 180 for both cohorts | ||
Other | Strength of the Bilateral Knee Flexors and Extensors During the Maximal Voluntary Isometric Strength Test. | Days 90 (Cohort 2), 120 (Cohort 1) and both Cohorts at Day 180, Months 12, 18 and 24 | ||
Other | Time Taken to Walk 100 Meters During the 100 Meter Walk Test. | Days 90 (Cohort 2), 120 (Cohort 1); both Cohorts at Day 180, Months 12, 18 and Cohort 2 at Month 24 | ||
Other | Score of Muscle Function Using the The North Star Ambulatory Assessment (NSAA). | The NSAA provides a score between 0 and 34 where higher numbers represent greater muscle function. | Days 90 (Cohort 2), 120 (Cohort 1) and both Cohorts at Day 180, Months 12, 18 and 24 | |
Primary | Number of Unanticipated Grade III or Higher Treatment-Related Toxicities | 2 years | ||
Secondary | Expression of GALGT2 as Demonstrated by Immunofluorescent Staining With Anti-CT Epitope Antibodies or WFA Lectin in Muscle Biopsy Sections at 120 Days Post Injection (Cohort 1) and 90 Days Post-injection (Cohort 2). | Percentage of fibers expressing GALGT2 in each biopsy sample. | Day 90 (Cohort 2) and Day 120 (Cohort 1) | |
Secondary | GALGT2 Protein Expression Quantified by Western Blot and Assessed by Densitometry in Muscle Biopsy Tissue at 120 Days Post-injection (Cohort 1) and 90 Days Post-injection (Cohort 2) | Day 90 (Cohort 2) and Day 120 (Cohort 1) |
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