Duchenne Muscular DystrophyPhase 1NCT02376816
Clinical Intramuscular Gene Transfer Trial of rAAVrh74.MCK.Micro-Dystrophin to Patients With Duchenne Muscular Dystrophy
A Phase 1 study testing rAAVrh74.MCK.micro-Dystrophin in people with Duchenne Muscular Dystrophy, run by Jerry R. Mendell at 1 site in United States.
Trial summary
The proposed phase I clinical trial is a pilot study to evaluate safety and biological activity of the rAAVrh74.MCK.micro-Dystrophin vector administered by an intramuscular route. This study will evaluated the micro-Dystrophin vector as a potential dystrophin replacement mechanism for Duchenne Muscular Dystrophy. Read more about this study
- Who is it for?
- Ages 7 years and older, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- rAAVrh74.MCK.micro-Dystrophin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to Sep 2017
- Phase
- Phase 1
- 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 7 years and older
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 7 or older; must be wheelchair-dependent
- Confirmed Dystrophin mutations based on mutation compatibility with micro-dys cDNA based on previously published methods.
- Males of any ethnic group will be eligible.
- Ability to cooperate with muscle testing.
- Willingness of sexually active subjects with reproductive capacity to practice reliable method of contraception (If appropriate).
Who cannot join
- Active viral infection based on clinical observations.
- 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
- Diagnosis of (or ongoing treatment for) an autoimmune disease
Show all 9Show fewer
- Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer.
- Subjects with AAVrh74 binding antibody titers ≥ 1:50 as determined by ELISA immunoassay.
- Abnormal laboratory values in the clinically significant range as defined in protocol or 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
About this study
Official title: Phase I Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.Micro-dystrophin
The proposed phase I clinical trial is a pilot study to evaluate safety and biological activity of the rAAVrh74.MCK.micro-Dystrophin vector administered by an intramuscular route. This study will evaluated the micro-Dystrophin vector as a potential dystrophin replacement mechanism for Duchenne Muscular Dystrophy. Two cohorts will undergo gene transfer in a standard three-six dose escalation scheme to establish maximum tolerated dose (MTD) using toxicity. A minimum of three subjects will be enrolled into each cohort. The first cohort will receive a total dose of 3E11 vg. The second cohort will receive 1E12 vg total dose.
Read the detailed description
The primary objective of this study is the assessment of the safety of an intramuscular administration of rAAVrh74.MCK.micro-Dystrophin to the Extensor Digitorum Brevis (EDB) muscle of patients with Duchenne Muscular Dystrophy (DMD). Safety will be assessed by changes in hematology, serum chemistry, urinalysis, immunologic response to rAAVrh74 and micro-Dystrophin protein, and reported history and observations of symptoms. Subjects will be evaluated at baseline, injection visit (days 0-2), and return for follow up visits on days 7, 14, 30,60, 90, and 180 and at the end of 1st and 2nd years. On Day 180, subjects will undergo a muscle biopsy on the injected muscles in one foot compared with placebo-treatment in the opposite foot to establish transgene expression and any potential toxicity from gene transfer.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- rAAVrh74.MCK.micro-Dystrophin
- Keywords
- DMD, muscular dystrophy, dystrophin
- Medical subject headings
- Muscular Dystrophy, Duchenne, Muscular Dystrophies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rAAVrh74.MCK.micro-DystrophinBiological
Recombinant adeno-associated virus carrying a truncated "micro" dystrophin transgene under control of a muscle specific MCK promoter.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Low Dose | Experimental | The rAAVrh74.MCK.micro-Dystrophin vector will be injected to the Extensor Digitorum Brevis (EDB) muscle of a single foot at a total dose of 3E11 vg. The contralateral EDB muscle will injected with normal saline placebo as a comparator. Both physician and study team will be blinded as to which muscle received vector vs placebo. A minimum of three (3) patients with DMD will be enrolled in this cohort. Receives: Biological: rAAVrh74.MCK.micro-Dystrophin |
| Cohort 2: High Dose | Experimental | The rAAVrh74.MCK.micro-Dystrophin vector will be injected to the Extensor Digitorum Brevis (EDB) muscle of a single foot at a total dose of 1E12 vg. The contralateral EDB muscle will injected with normal saline placebo as a comparator. Both physician and study team will be blinded as to which muscle received vector vs placebo. A minimum of three (3) patients with DMD will be enrolled in this cohort. Receives: Biological: rAAVrh74.MCK.micro-Dystrophin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety based on number of participants with adverse events
AEs will be monitored and scored for severity and relatedness to the study article.
Measured: 2 years
Secondary outcomes (1)
Transgene Expression
Biologic activity of the vector will be measured by immunohistochemistry detection of dystrophin on muscle biopsies as compared to placebo treated controls.
Measured: 180 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2015 (estimated)
- Study startMar 2015
- Primary completionSep 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jerry R. Mendell
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor-investigator, Jerry R. Mendell, Nationwide Children's Hospital
- Investigators
- Jerry R Mendell, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02376816
- Sponsor's protocol ID
- 14-00718
- Status last verified
- Nov 2017
- First submitted
- 26 Feb 2015
- Last updated
- 24 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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 21194036Rodino-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 19904237Rodino-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
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.Micro-dystrophin
- ClinicalTrials.gov ID
- NCT02376816
- Acronym / sponsor ID
- 14-00718
- Conditions
- Duchenne Muscular Dystrophy
- Keywords
- DMD, muscular dystrophy, dystrophin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Jerry R. MendellUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Mar 2015
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 3 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed phase I clinical trial is a pilot study to evaluate safety and biological activity of the rAAVrh74.MCK.micro-Dystrophin vector administered by an intramuscular route. This study will evaluated the micro-Dystrophin vector as a potential dystrophin replacement mechanism for Duchenne Muscular Dystrophy. Two cohorts will undergo gene transfer in a standard three-six dose escalation scheme to establish maximum tolerated dose (MTD) using toxicity. A minimum of three subjects will be enrolled into each cohort. The first cohort will receive a total dose of 3E11 vg. The second cohort will receive 1E12 vg total dose.
Detailed description
The primary objective of this study is the assessment of the safety of an intramuscular administration of rAAVrh74.MCK.micro-Dystrophin to the Extensor Digitorum Brevis (EDB) muscle of patients with Duchenne Muscular Dystrophy (DMD). Safety will be assessed by changes in hematology, serum chemistry, urinalysis, immunologic response to rAAVrh74 and micro-Dystrophin protein, and reported history and observations of symptoms. Subjects will be evaluated at baseline, injection visit (days 0-2), and return for follow up visits on days 7, 14, 30,60, 90, and 180 and at the end of 1st and 2nd years. On Day 180, subjects will undergo a muscle biopsy on the injected muscles in one foot compared with placebo-treatment in the opposite foot to establish transgene expression and any potential toxicity from gene transfer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Low Dose | Experimental | Biological: rAAVrh74.MCK.micro-DystrophinThe rAAVrh74.MCK.micro-Dystrophin vector will be injected to the Extensor Digitorum Brevis (EDB) muscle of a single foot at a total dose of 3E11 vg. The contralateral EDB muscle will injected with normal saline placebo as a comparator. Both physician and study team will be blinded as to which muscle received vector vs placebo. A minimum of three (3) patients with DMD will be enrolled in this cohort. |
| Cohort 2: High Dose | Experimental | Biological: rAAVrh74.MCK.micro-DystrophinThe rAAVrh74.MCK.micro-Dystrophin vector will be injected to the Extensor Digitorum Brevis (EDB) muscle of a single foot at a total dose of 1E12 vg. The contralateral EDB muscle will injected with normal saline placebo as a comparator. Both physician and study team will be blinded as to which muscle received vector vs placebo. A minimum of three (3) patients with DMD will be enrolled in this cohort. |
Who may qualify
- Ages
- 7 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Age 7 or older; must be wheelchair-dependent
- Confirmed Dystrophin mutations based on mutation compatibility with micro-dys cDNA based on previously published methods.
- Males of any ethnic group will be eligible.
- Ability to cooperate with muscle testing.
- Willingness of sexually active subjects with reproductive capacity to practice reliable method of contraception (If appropriate).
Key exclusion criteria (9 listed)
- Active viral infection based on clinical observations.
- Symptoms or signs of cardiomyopathy, including:
- Serological evidence of HIV infection, or Hepatitis A, B or C infection
- Diagnosis of (or ongoing treatment for) an autoimmune disease
- Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rAAVrh74.MCK.micro-DystrophinRecombinant adeno-associated virus carrying a truncated "micro" dystrophin transgene under control of a muscle specific MCK promoter. | Biological | Cohort 1: Low Dose, Cohort 2: High Dose |
Primary outcome
Safety based on number of participants with adverse events
Time frame: 2 years
AEs will be monitored and scored for severity and relatedness to the study article.
1 secondary outcome
Transgene Expression
Time frame: 180 Days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2017.
- Background: PubMed 21194036Rodino-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.
- Background: PubMed 19904237Rodino-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.
- Background: PubMed 17892583Rodino-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.
- Center for Gene Therapy, The Research Institute at Nationwide Children's HospitalLink provided by the sponsor.
- Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center at Nationwide Children's HospitalLink provided by the sponsor.
- Gene Therapy Clinical Studies at Nationwide Children's HospitalLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jerry R Mendell, MD principal investigator
Nationwide Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing rAAVrh74.MCK.micro-Dystrophin in people with Duchenne Muscular Dystrophy, run by Jerry R. Mendell 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 5 inclusion and 9 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 24 Nov 2017. 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety based on number of participants with adverse events (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 NCT02376816, which also lists 3 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 24 Nov 2017.