Gene Transfer Clinical Trial to Deliver rAAVrh74.MCK.GALGT2 for Duchenne Muscular Dystrophy
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ClinicalTrials.gov Identifier: NCT03333590 |
Recruitment Status :
Active, not recruiting
First Posted : November 7, 2017
Results First Posted : April 25, 2022
Last Update Posted : April 25, 2022
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Condition or disease | Intervention/treatment | Phase |
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Duchenne Muscular Dystrophy | Biological: rAAVrh74.MCK.GALGT2 | Phase 1 Phase 2 |
This is an open-label, dose escalation trial where the vector will be delivered via the femoral artery to the muscles of both legs of DMD subjects.
The primary objective of this study is the assessment of the safety of intravascular administration of rAAVrh74.MCK.GALGT2 to DMD patients. Safety endpoints will be assessed by changes in hematology, serum chemistry, urinalysis, immunologic response to rAAVrh74 and GALGT2, and reported history and observations of symptoms. Efficacy measures will be used as secondary outcome for this disorder including a combination of functional 6 minute walk test (6MWT) and direct muscle testing for strength (MVICT) of lower limb muscles.
Subjects will be evaluated at baseline, infusion visit (days 0-2), and return for follow up visits on days 7, 14, 30, 60, 90, and 180 and months 12, 18 and 24
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 2 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | This is a dose escalation trial that will begin with the minimal efficacious dose as determined by preclinical studies and approved by the FDA. During the course of the trial, if safety is shown the dose will be escalated according to the clinical protocol. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase I/IIa Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.GALGT2 |
Actual Study Start Date : | November 6, 2017 |
Actual Primary Completion Date : | November 4, 2020 |
Estimated Study Completion Date : | June 2022 |

Arm | Intervention/treatment |
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Experimental: Cohort 1 (Minimal Efficacious Dose) rAAVrh74.MCK.GALGT2
N = 3 [2.5 x E13 vg/kg per leg, delivered bilaterally (total 5.0 x E13 vg/kg)]
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Biological: rAAVrh74.MCK.GALGT2
Adeno-associated virus serotype rh74 carrying the GALGT2 gene under the control of a MCK promoter (rAAVrh74.MCK.GALGT2) will be delivered one time to each of the lower limbs through the femoral artery using an intravascular limb infusion technique (ILI) |
Experimental: Cohort 2 (Dose Escalation) rAAVrh74.MCK.GALGT2
N=3 [5 x E13 vg/kg per leg, delivered bilaterally (total 1.0 x E14 vg/kg)]
|
Biological: rAAVrh74.MCK.GALGT2
Adeno-associated virus serotype rh74 carrying the GALGT2 gene under the control of a MCK promoter (rAAVrh74.MCK.GALGT2) will be delivered one time to each of the lower limbs through the femoral artery using an intravascular limb infusion technique (ILI) |
- Number of Unanticipated Grade III or Higher Treatment-Related Toxicities [ Time Frame: 2 years ]
- 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). [ Time Frame: Day 90 (Cohort 2) and Day 120 (Cohort 1) ]Percentage of fibers expressing GALGT2 in each biopsy sample.
- 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) [ Time Frame: Day 90 (Cohort 2) and Day 120 (Cohort 1) ]
- Number of Meters Walked During the 6 Minute Walk Test [ Time Frame: Day 90 (Cohort 2) and Day 120 (Cohort 1) and Day 180 for both cohorts ]
- Strength of the Bilateral Knee Flexors and Extensors During the Maximal Voluntary Isometric Strength Test. [ Time Frame: Days 90 (Cohort 2), 120 (Cohort 1) and both Cohorts at Day 180, Months 12, 18 and 24 ]
- Time Taken to Walk 100 Meters During the 100 Meter Walk Test. [ Time Frame: Days 90 (Cohort 2), 120 (Cohort 1); both Cohorts at Day 180, Months 12, 18 and Cohort 2 at Month 24 ]
- Score of Muscle Function Using the The North Star Ambulatory Assessment (NSAA). [ Time Frame: Days 90 (Cohort 2), 120 (Cohort 1) and both Cohorts at Day 180, Months 12, 18 and 24 ]The NSAA provides a score between 0 and 34 where higher numbers represent greater muscle function.

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Ages Eligible for Study: | 4 Years and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | Male |
Accepts Healthy Volunteers: | No |
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
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• 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
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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

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): NCT03333590
United States, Ohio | |
Nationwide Children's Hospital | |
Columbus, Ohio, United States, 43205 |
Principal Investigator: | Kevin Flanigan, MD | Nationwide Children's Hospital |
Documents provided by Kevin Flanigan, Nationwide Children's Hospital:
Responsible Party: | Kevin Flanigan, Professor of Pediatrics, Nationwide Children's Hospital |
ClinicalTrials.gov Identifier: | NCT03333590 |
Other Study ID Numbers: |
GALGT2 Gene Therapy for DMD |
First Posted: | November 7, 2017 Key Record Dates |
Results First Posted: | April 25, 2022 |
Last Update Posted: | April 25, 2022 |
Last Verified: | April 2022 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
DMD Duchenne Muscular Dystrophy |
Muscular Dystrophies Muscular Dystrophy, Duchenne Muscular Disorders, Atrophic Muscular Diseases Musculoskeletal Diseases |
Neuromuscular Diseases Nervous System Diseases Genetic Diseases, Inborn Genetic Diseases, X-Linked |