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Duchenne Muscular DystrophyPhase 1/2NCT02704325

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

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.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The proposed clinical trial study of rAAVrh74.MCK.GALGT2 for duchenne muscular dystrophy (DMD) patients that will involve direct intramuscular injection to the extensor digitorum brevis muscle (EDB). Read more about this study

Who is it for?
Ages 9 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?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteUnited States
Study dates
Apr 2016to Feb 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

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

Who may be able to join

  • Nonambulant subjects, age 9 or older
  • Confirmed mutation in the DMD gene using a clinically accepted technique that completely defines the mutation
  • A magnetic resonance image of the EDB showing preservation of sufficient muscle mass to permit transfection
  • Males of any ethnic group will be eligible
  • Ability to cooperate with all study procedures
  • Willingness of sexually active subjects with reproductive capacity to practice reliable method of contraception (If appropriate).
  • Stable dose of corticosteroid therapy (including either prednisone or deflazacort and 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
  • 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 A, B or C infection
Show all 12Show fewer
  • 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 ≥ 1:400 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 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 that will involve direct intramuscular injection to the extensor digitorum brevis muscle (EDB).

Read the detailed description

This is a phase I safety and tolerability study. Three DMD subjects will receive bilateral injections into the EDB muscle, with one EDB receiving the GALGT2 vector (rAAVrh74.MCK.GALGT2) and the other side receiving saline alone (assigned in a randomized fashion). Three subjects will receive a single gene transfer dose of 1E12 vector genomes, and patients and investigators will be blinded as to which muscle is injected with vector. Muscle biopsies will be performed at three months (12 weeks) in two subjects and at 1.5 months (6 weeks) in one subject and evaluated blindly for the expression of the GALGT2 transgene.

Being tested
rAAVrh74.MCK.GALGT2, PLACEBO (Saline)
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

    Direct intramuscular injection of rAAVrh74.MCK.GALGT2 transferred to the extensor digitorum brevis muscle (EDB) of one foot and the other side receiving saline alone.

  • PLACEBO (Saline)Other

    Direct intramuscular injection of rAAVrh74.MCK.GALGT2 transferred to the extensor digitorum brevis muscle (EDB) of one foot and the OTHER side receiving saline alone.

Study groups in NCT02704325
Study groupRoleWhat they receive
GALGT2 Viral VectorExperimentalDose: 1E12 vg (total dose) (n=3) of rAAVrh74.MCK.GALGT2 vs Placebo (Saline). All participants will receive rAAVrh74.MCK.GALGT2 in the right or the left EDB muscle and receive Saline in the opposite EDB muscles. The investigator will not know which side will receive rAAVrh74.MCK.GALGT2 vs Saline until after the trial is over. At the end of the trial the investigator will be unblinded.
Receives: Biological: rAAVrh74.MCK.GALGT2
SalineExperimentalDose: 1E12 vg (total dose) (n=3) of rAAVrh74.MCK.GALGT2 vs Placebo (Saline). All participants will receive rAAVrh74.MCK.GALGT2 in the right or the left EDB muscle and receive Saline in the opposite EDB muscles. The investigator will not know which side will receive rAAVrh74.MCK.GALGT2 vs Saline until after the trial is over. At the end of the trial the investigator will be unblinded.
Receives: Other: PLACEBO (Saline)

What is being measured

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

  1. Treatment related toxicities

    Based on the development of unacceptable toxicity defined as the occurrence of any one Grade III or higher treatment-related toxicities.

    Measured: 2 years

Secondary outcomes (9)

  1. Expression of GALGT2 demonstrated with anti-CT epitope antibodies.

    Measured: 6 or 12 weeks

  2. GALGT2 protein expression quantified by western blot and assessed by densitometry

    Measured: 6 or 12 weeks

  3. Transduction efficiency measured by qPCR of the GALGT transgene from muscle, and expressed as vector genomes normalized to a genomic single-copy control.

    Measured: 6 or 12 weeks

  4. Number of fibers containing central nuclei compared between muscles by paired t-tests

    Measured: 6 or 12 weeks

  5. Dystrophin expression demonstrated with antibodies to N-terminal, C-terminal, and rod domains

    Measured: 6 or 12 weeks

  6. Utrophin expression

    Measured: 6 or 12 weeks

  7. Leukocyte markers including CD45, CD3, CD4, CD8, and MAC 387

    Measured: 6 or 12 weeks

  8. Muscle will be examined for histological appearance

    Measured: 6 or 12 weeks

  9. Antibodies to rAAVrh74 along with PBMC ELISpots to both rAAVrh74 capsid and GALGT protein will be evaluated at different time points during the study

    Measured: 6 or 12 weeks

Timeline

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

  1. First posted10 Mar 2016 (estimated)
  2. Study startApr 2016 (estimated)
  3. Primary completionJul 2018 (estimated)
  4. Study completionFeb 2020 (estimated)

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02704325
Sponsor's protocol ID
GALGT2 for DMD
Status last verified
Feb 2018
First submitted
23 Dec 2015
Last updated
6 Feb 2018
Results posted
No
Data monitoring committee
Yes
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

  • Martin PT, Xu R, Rodino-Klapac LR, Oglesbay E, Camboni M, Montgomery CL, Shontz K, Chicoine LG, Clark KR, Sahenk Z, Mendell JR, Janssen PM. Overexpression of Galgt2 in skeletal muscle prevents injury resulting from eccentric contractions in both mdx and wild-type mice. Am J Physiol Cell Physiol. 2009 Mar;296(3):C476-88. doi: 10.1152/ajpcell.00456.2008. Epub 2008 Dec 24.

    PubMed 19109526

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 7 inclusion and 12 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: withdrawn, as of the sponsor's last update on 6 Feb 2018. 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

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 NCT02704325, which also lists 2 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 6 Feb 2018.

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