Duchenne Muscular DystrophyPhase 1NCT00428935
Safety Study of Mini-dystrophin Gene to Treat Duchenne Muscular Dystrophy
A Phase 1 study testing rAAV2.5-CMV-minidystrophin (d3990) in people with Duchenne Muscular Dystrophy, run by Nationwide Children's Hospital at 1 site in United States.
Trial summary
The purpose of this study is to determine the safety of a miniature dystrophin gene in the treatment of progressive muscle weakness due to Duchenne Muscular Dystrophy (DMD). Read more about this study
- Who is it for?
- Ages 5 to 15 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- rAAV2.5-CMV-minidystrophin (d3990)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2006to Jul 2010
- 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 5 to 15 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Known null mutation of the Dystrophin gene
- Male age of 5 years or older
- If taking corticosteroids, must have dose unchanged for the past 3 months
- Serum creatine kinase elevation greater than 10x normal value (established by Children's Hospital)
- Progressive, symmetrical proximal muscle weakness of arms and legs
Who cannot join
- Unable to cooperate for muscle strength testing
- Joint contractures that prohibit muscle strength testing
- Concomitant illness
- Individuals predisposed to excessive vagal responses (bradyarrhythmia or hypotension)
- Controlled substance abuse
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1 Clinical Trial of rAAV2.5-CMV-mini-Dystrophin Gene Vector in Duchenne Muscular Dystrophy
The purpose of this study is to determine the safety of a miniature dystrophin gene in the treatment of progressive muscle weakness due to Duchenne Muscular Dystrophy (DMD).
Read the detailed description
This phase I randomized double blind dose escalation study investigates the safety and efficacy of the mini-dystrophin gene transferred to the biceps muscle for Duchenne muscular dystrophy patients, ages 5 to 12 years of age, using a recombinant adeno-associated virus. Eligible participants must have a known dystrophin gene mutation and may be concurrently treated with corticoid steroids. The mini-dystrophin gene or a placebo agent (normal saline or empty viral capsids) are injected directly into both biceps muscles while under conscious sedation. Following the gene transfer, patients are admitted to the hospital for 48 hours of observation followed by weekly outpatient visits at the Columbus Children's Hospital Neuromuscular Clinic. A bilateral muscle biopsy is preformed following 6 weeks with long term follow up will consisting of bi-annual visits for the next 2 years.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- rAAV2.5-CMV-minidystrophin (d3990)
- Keywords
- Duchenne, Muscle, Muscular Dystrophy, Gene Therapy, Dystrophin, Adeno-Associated Virus, AAV
- 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.
rAAV2.5-CMV-minidystrophin (d3990)Biological
Recombinant adeno-associated virus (AAV) carrying a truncated human dystrophin gene (mini-dystrophin) expressed from a cytomegalovirus (CMV) promoter.
| Study group | Role | What they receive |
|---|---|---|
| Low Dose | Experimental | Low dose cohort - 2.0E10 vg/kg Receives: Biological: rAAV2.5-CMV-minidystrophin (d3990) |
| High Dose | Experimental | High Dose - 1.0E11 vg/kg Receives: Biological: rAAV2.5-CMV-minidystrophin (d3990) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Physical Exams assessing major organ systems and safety labs (GGT, Bilirubin, Glucose, Amylase, CBC/Diff, AFP, Platelets, PT/PTT, Creatinine, Electrolytes, Total protein, Alkaline phosphatase, and Urinalysis)
Measured: followed for 2 years post injection
Secondary outcomes (2)
mini-dystrophin gene expression at the site of gene transfer
Measured: 90 days post injection
Maximal Volume Isometric Contraction Testing as a measure of muscle strength
Measured: out to 2 years post injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2007 (estimated)
- Study startMar 2006
- Primary completionMar 2009
- Study completionJul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- 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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- AskBio Inc
- Responsible party
- Principal 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
- NCT00428935
- Sponsor's protocol ID
- CCRI IRB05-00118
- Status last verified
- Feb 2013
- First submitted
- 26 Jan 2007
- Last updated
- 5 Feb 2013
- Results posted
- No
Publications
Watchko J, O'Day T, Wang B, Zhou L, Tang Y, Li J, Xiao X. Adeno-associated virus vector-mediated minidystrophin gene therapy improves dystrophic muscle contractile function in mdx mice. Hum Gene Ther. 2002 Aug 10;13(12):1451-60. doi: 10.1089/10430340260185085.
PubMed 12215266Wang B, Li J, Xiao X. Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13714-9. doi: 10.1073/pnas.240335297.
PubMed 11095710Mendell JR, Campbell K, Rodino-Klapac L, Sahenk Z, Shilling C, Lewis S, Bowles D, Gray S, Li C, Galloway G, Malik V, Coley B, Clark KR, Li J, Xiao X, Samulski J, McPhee SW, Samulski RJ, Walker CM. Dystrophin immunity in Duchenne's muscular dystrophy. N Engl J Med. 2010 Oct 7;363(15):1429-37. doi: 10.1056/NEJMoa1000228.
PubMed 20925545Bowles DE, McPhee SW, Li C, Gray SJ, Samulski JJ, Camp AS, Li J, Wang B, Monahan PE, Rabinowitz JE, Grieger JC, Govindasamy L, Agbandje-McKenna M, Xiao X, Samulski RJ. Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol Ther. 2012 Feb;20(2):443-55. doi: 10.1038/mt.2011.237. Epub 2011 Nov 8.
PubMed 22068425
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Clinical Trial of rAAV2.5-CMV-mini-Dystrophin Gene Vector in Duchenne Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT00428935
- Acronym / sponsor ID
- CCRI IRB05-00118
- Conditions
- Duchenne Muscular Dystrophy
- Keywords
- Duchenne, Muscle, Muscular Dystrophy, Gene Therapy, Dystrophin, Adeno-Associated Virus, AAV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Collaborators
- AskBio Inc
- Study start
- Mar 2006
- Primary completion
- Mar 2009 (actual)
- Study completion
- Jul 2010 (actual)
- First posted
- 30 Jan 2007 (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 purpose of this study is to determine the safety of a miniature dystrophin gene in the treatment of progressive muscle weakness due to Duchenne Muscular Dystrophy (DMD).
Detailed description
This phase I randomized double blind dose escalation study investigates the safety and efficacy of the mini-dystrophin gene transferred to the biceps muscle for Duchenne muscular dystrophy patients, ages 5 to 12 years of age, using a recombinant adeno-associated virus. Eligible participants must have a known dystrophin gene mutation and may be concurrently treated with corticoid steroids. The mini-dystrophin gene or a placebo agent (normal saline or empty viral capsids) are injected directly into both biceps muscles while under conscious sedation. Following the gene transfer, patients are admitted to the hospital for 48 hours of observation followed by weekly outpatient visits at the Columbus Children's Hospital Neuromuscular Clinic. A bilateral muscle biopsy is preformed following 6 weeks with long term follow up will consisting of bi-annual visits for the next 2 years.
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 |
|---|---|---|
| Low Dose | Experimental | Biological: rAAV2.5-CMV-minidystrophin (d3990)Low dose cohort - 2.0E10 vg/kg |
| High Dose | Experimental | Biological: rAAV2.5-CMV-minidystrophin (d3990)High Dose - 1.0E11 vg/kg |
Who may qualify
- Ages
- 5 to 15 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Known null mutation of the Dystrophin gene
- Male age of 5 years or older
- If taking corticosteroids, must have dose unchanged for the past 3 months
- Serum creatine kinase elevation greater than 10x normal value (established by Children's Hospital)
- Progressive, symmetrical proximal muscle weakness of arms and legs
Key exclusion criteria (5 listed)
- Unable to cooperate for muscle strength testing
- Joint contractures that prohibit muscle strength testing
- Concomitant illness
- Individuals predisposed to excessive vagal responses (bradyarrhythmia or hypotension)
- Controlled substance abuse
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 |
|---|---|---|
| rAAV2.5-CMV-minidystrophin (d3990)Recombinant adeno-associated virus (AAV) carrying a truncated human dystrophin gene (mini-dystrophin) expressed from a cytomegalovirus (CMV) promoter. | Biological | High Dose, Low Dose |
Primary outcome
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: followed for 2 years post injection
Physical Exams assessing major organ systems and safety labs (GGT, Bilirubin, Glucose, Amylase, CBC/Diff, AFP, Platelets, PT/PTT, Creatinine, Electrolytes, Total protein, Alkaline phosphatase, and Urinalysis)
2 secondary outcomes
mini-dystrophin gene expression at the site of gene transfer
Time frame: 90 days post injection
Maximal Volume Isometric Contraction Testing as a measure of muscle strength
Time frame: out to 2 years post injection
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 5 Feb 2013.
- Background: PubMed 12215266Watchko J, O'Day T, Wang B, Zhou L, Tang Y, Li J, Xiao X. Adeno-associated virus vector-mediated minidystrophin gene therapy improves dystrophic muscle contractile function in mdx mice. Hum Gene Ther. 2002 Aug 10;13(12):1451-60. doi: 10.1089/10430340260185085.
- Background: PubMed 11095710Wang B, Li J, Xiao X. Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13714-9. doi: 10.1073/pnas.240335297.
- Results publication: PubMed 20925545Mendell JR, Campbell K, Rodino-Klapac L, Sahenk Z, Shilling C, Lewis S, Bowles D, Gray S, Li C, Galloway G, Malik V, Coley B, Clark KR, Li J, Xiao X, Samulski J, McPhee SW, Samulski RJ, Walker CM. Dystrophin immunity in Duchenne's muscular dystrophy. N Engl J Med. 2010 Oct 7;363(15):1429-37. doi: 10.1056/NEJMoa1000228.
- Results publication: PubMed 22068425Bowles DE, McPhee SW, Li C, Gray SJ, Samulski JJ, Camp AS, Li J, Wang B, Monahan PE, Rabinowitz JE, Grieger JC, Govindasamy L, Agbandje-McKenna M, Xiao X, Samulski RJ. Phase 1 gene therapy for Duchenne muscular dystrophy using a translational optimized AAV vector. Mol Ther. 2012 Feb;20(2):443-55. doi: 10.1038/mt.2011.237. Epub 2011 Nov 8.
- Columbus Children's Research InstituteLink provided by the sponsor.
- Asklepios BioPharmaceutical Inc.Link 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 rAAV2.5-CMV-minidystrophin (d3990) in people with Duchenne Muscular Dystrophy, run by Nationwide Children's Hospital 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 5 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 5 Feb 2013. 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?
Number of Participants with Adverse Events as a Measure of Safety and Tolerability (time frame: followed for 2 years post injection). 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 NCT00428935, which also lists 4 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 5 Feb 2013.