Gene Transfer Clinical Trial to Deliver rAAVrh74.MCK.GALGT2 for Duchenne Muscular Dystrophy

NCT03333590 | Completed Phase 1 Results FDA Drug

• 1 other identifier: GALGT2 Gene Therapy for DMD
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Duchenne Muscular Dystrophy

Keywords

DMD; Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (1)

• Number of Unanticipated Grade III or Higher Treatment-Related Toxicities

  2 years

Secondary Outcomes (2)

• 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).

  Day 90 (Cohort 2) and Day 120 (Cohort 1)

• 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)

Other Outcomes (4)

• 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

• 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

• 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

Study Arms (2)

Cohort 1 (Minimal Efficacious Dose) rAAVrh74.MCK.GALGT2

EXPERIMENTAL

N = 3 \[2.5 x E13 vg/kg per leg, delivered bilaterally (total 5.0 x E13 vg/kg)\]

Biological: rAAVrh74.MCK.GALGT2

Cohort 2 (Dose Escalation) rAAVrh74.MCK.GALGT2

EXPERIMENTAL

N=3 \[5 x E13 vg/kg per leg, delivered bilaterally (total 1.0 x E14 vg/kg)\]

Biological: rAAVrh74.MCK.GALGT2

Interventions

rAAVrh74.MCK.GALGT2 BIOLOGICAL

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)

Cohort 1 (Minimal Efficacious Dose) rAAVrh74.MCK.GALGT2; Cohort 2 (Dose Escalation) rAAVrh74.MCK.GALGT2

Eligibility Criteria

• Age: 4 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kevin Flanigan: lead

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (35)

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MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Dr. Kevin Flanigan
• Organization: Abigail Wexner Research Institute at Nationwide Children's Hospital

kevin.flanigan@nationwidechildrens.org

614-355-2947

Study Officials

• Kevin Flanigan, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: November 1, 2017
• First Posted: November 7, 2017
• Study Start: November 6, 2017
• Primary Completion: November 4, 2020
• Study Completion: December 31, 2023
• Last Updated: March 13, 2025
• Results First Posted: April 25, 2022

Record last verified: 2025-02

Locations

US (1)