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Duchenne Muscular DystrophyPhase 1/2NCT03333590

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

A Phase 1/2 study testing rAAVrh74.MCK.GALGT2 in people with Duchenne Muscular Dystrophy, run by Kevin Flanigan at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 4 years and older, men only
Conditions the study is for
Duchenne Muscular Dystrophy
What is being tested?
rAAVrh74.MCK.GALGT2
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
6 Nov 2017to 31 Dec 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 4 years and older
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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%
Show all 13Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

Other trials in United States

About this study

Official title: Phase I/IIa Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.GALGT2

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.

Read the detailed description

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

Being tested
rAAVrh74.MCK.GALGT2
Keywords
DMD, Duchenne Muscular Dystrophy
Medical subject headings
Muscular Dystrophy, Duchenne

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rAAVrh74.MCK.GALGT2Biological

    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)

Study groups in NCT03333590
Study groupRoleWhat they receive
Cohort 1 (Minimal Efficacious Dose) rAAVrh74.MCK.GALGT2ExperimentalN = 3 [2.5 x E13 vg/kg per leg, delivered bilaterally (total 5.0 x E13 vg/kg)]
Receives: Biological: rAAVrh74.MCK.GALGT2
Cohort 2 (Dose Escalation) rAAVrh74.MCK.GALGT2ExperimentalN=3 [5 x E13 vg/kg per leg, delivered bilaterally (total 1.0 x E14 vg/kg)]
Receives: Biological: rAAVrh74.MCK.GALGT2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Unanticipated Grade III or Higher Treatment-Related Toxicities

    Measured: 2 years

Secondary outcomes (2)
  1. 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.

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

  2. 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)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Nov 2017
  2. Study start6 Nov 2017
  3. Primary completion4 Nov 2020
  4. Study completion31 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
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)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03333590
Sponsor's protocol ID
GALGT2 Gene Therapy for DMD
Status last verified
Feb 2025
First submitted
1 Nov 2017
Last updated
13 Mar 2025
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Chicoine LG, Rodino-Klapac LR, Shao G, Xu R, Bremer WG, Camboni M, Golden B, Montgomery CL, Shontz K, Heller KN, Griffin DA, Lewis S, Coley BD, Walker CM, Clark KR, Sahenk Z, Mendell JR, Martin PT. Vascular delivery of rAAVrh74.MCK.GALGT2 to the gastrocnemius muscle of the rhesus macaque stimulates the expression of dystrophin and laminin alpha2 surrogates. Mol Ther. 2014 Apr;22(4):713-24. doi: 10.1038/mt.2013.246. Epub 2013 Oct 22.

    PubMed 24145553
  • Flanigan KM, Dunn DM, von Niederhausern A, Soltanzadeh P, Gappmaier E, Howard MT, Sampson JB, Mendell JR, Wall C, King WM, Pestronk A, Florence JM, Connolly AM, Mathews KD, Stephan CM, Laubenthal KS, Wong BL, Morehart PJ, Meyer A, Finkel RS, Bonnemann CG, Medne L, Day JW, Dalton JC, Margolis MK, Hinton VJ; United Dystrophinopathy Project Consortium; Weiss RB. Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort. Hum Mutat. 2009 Dec;30(12):1657-66. doi: 10.1002/humu.21114.

    PubMed 19937601
  • Flanigan KM, von Niederhausern A, Dunn DM, Alder J, Mendell JR, Weiss RB. Rapid direct sequence analysis of the dystrophin gene. Am J Hum Genet. 2003 Apr;72(4):931-9. doi: 10.1086/374176. Epub 2003 Mar 11.

    PubMed 12632325
  • Seinen JM, Hoekstra HJ. Isolated limb perfusion of soft tissue sarcomas: a comprehensive review of literature. Cancer Treat Rev. 2013 Oct;39(6):569-77. doi: 10.1016/j.ctrv.2012.10.005. Epub 2012 Dec 8.

    PubMed 23232098
  • Rodino-Klapac LR, Janssen PM, Montgomery CL, Coley BD, Chicoine LG, Clark KR, Mendell JR. A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy. J Transl Med. 2007 Sep 24;5:45. doi: 10.1186/1479-5876-5-45.

    PubMed 17892583
  • Rodino-Klapac LR, Montgomery CL, Bremer WG, Shontz KM, Malik V, Davis N, Sprinkle S, Campbell KJ, Sahenk Z, Clark KR, Walker CM, Mendell JR, Chicoine LG. Persistent expression of FLAG-tagged micro dystrophin in nonhuman primates following intramuscular and vascular delivery. Mol Ther. 2010 Jan;18(1):109-17. doi: 10.1038/mt.2009.254. Epub 2009 Nov 10.

    PubMed 19904237
  • Rodino-Klapac LR, Montgomery CL, Mendell JR, Chicoine LG. AAV-mediated gene therapy to the isolated limb in rhesus macaques. Methods Mol Biol. 2011;709:287-98. doi: 10.1007/978-1-61737-982-6_19.

    PubMed 21194036
  • Mendell JR, Shilling C, Leslie ND, Flanigan KM, al-Dahhak R, Gastier-Foster J, Kneile K, Dunn DM, Duval B, Aoyagi A, Hamil C, Mahmoud M, Roush K, Bird L, Rankin C, Lilly H, Street N, Chandrasekar R, Weiss RB. Evidence-based path to newborn screening for Duchenne muscular dystrophy. Ann Neurol. 2012 Mar;71(3):304-13. doi: 10.1002/ana.23528.

    PubMed 22451200
  • Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Miller JP, Province MA. Clinical investigation in Duchenne dystrophy: 2. Determination of the "power" of therapeutic trials based on the natural history. Muscle Nerve. 1983 Feb;6(2):91-103. doi: 10.1002/mus.880060204.

    PubMed 6343858
  • Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Neuromuscul Disord. 2002 Dec;12(10):926-9. doi: 10.1016/s0960-8966(02)00140-2.

    PubMed 12467747
  • Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell. 1987 Jul 31;50(3):509-17. doi: 10.1016/0092-8674(87)90504-6.

    PubMed 3607877
  • Bonilla E, Samitt CE, Miranda AF, Hays AP, Salviati G, DiMauro S, Kunkel LM, Hoffman EP, Rowland LP. Duchenne muscular dystrophy: deficiency of dystrophin at the muscle cell surface. Cell. 1988 Aug 12;54(4):447-52. doi: 10.1016/0092-8674(88)90065-7.

    PubMed 3042151
  • Oudet C, Hanauer A, Clemens P, Caskey T, Mandel JL. Two hot spots of recombination in the DMD gene correlate with the deletion prone regions. Hum Mol Genet. 1992 Nov;1(8):599-603. doi: 10.1093/hmg/1.8.599.

    PubMed 1363782
  • Beggs AH, Koenig M, Boyce FM, Kunkel LM. Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Hum Genet. 1990 Nov;86(1):45-8. doi: 10.1007/BF00205170.

    PubMed 2253937
  • Chamberlain JS, Gibbs RA, Ranier JE, Nguyen PN, Caskey CT. Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res. 1988 Dec 9;16(23):11141-56. doi: 10.1093/nar/16.23.11141.

    PubMed 3205741

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing rAAVrh74.MCK.GALGT2 in people with Duchenne Muscular Dystrophy, run by Kevin Flanigan at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Unanticipated Grade III or Higher Treatment-Related Toxicities (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03333590, which also lists 35 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2025.

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