Duchenne Muscular DystrophyPhase 1/2NCT04240314
AAV9 U7snRNA Gene Therapy to Treat Boys With DMD Exon 2 Duplications.
A Phase 1/2 study testing scAAV9.U7.ACCA in people with Duchenne Muscular Dystrophy, run by Megan Waldrop at 1 site in United States.
Trial summary
Open-label, single dose clinical trial of scAAV9.U7.ACCA via peripheral limb vein injection for Duchenne muscular dystrophy boys who have a duplication of exon 2. Read more about this study
- Who is it for?
- Ages 6 months to 13 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- scAAV9.U7.ACCA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2020to 1 Jul 2025
- 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 6 months to 13 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Age greater than 6 months and less than 14 years
- Confirmed duplication of exon 2 in the DMD gene using a clinically accepted technique that completely defines the mutation
- Pre-ambulant (not yet walking) or ambulant (as defined by the ability to walk 10 meters without assistance)
- Males of any ethnic group will be eligible
- Ability to cooperate with muscle testing
- In subjects age 4 and above, stable dose and regimen of corticosteroid therapy (prednisone, deflazacort, or their generic forms) for at least 12 weeks prior to gene transfer.
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 B or C infection
- Diagnosis of (or ongoing treatment for) an autoimmune disease
Show all 10Show fewer
- 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 SI creates unnecessary risks for gene transfer
- AAV9 binding antibody titers ≥ 1:400 as determined by ELISA immunoassay
- Abnormal laboratory values in the clinically significant range as listed in Table 7, 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/IIa Systemic Gene Delivery Clinical Trial of scAAV9.U7.ACCA for Exon 2 Duplication-Associated Duchenne Muscular Dystrophy
Open-label, single dose clinical trial of scAAV9.U7.ACCA via peripheral limb vein injection for Duchenne muscular dystrophy boys who have a duplication of exon 2.
Read the detailed description
The proposed clinical trial is a systemic (intravenous) delivery of scAAV9.U7.ACCA for DMD patients with a duplication of exon 2 in the DMD gene. Preclinical data shows that the small nuclear RNA (snRNA) construct delivered by the scAAV9.U7.ACCA vector causes significant skipping of exon 2, resulting in exclusion of the exon from the mature messenger RNA (mRNA) with a high degree of efficiency, leading to mRNA containing only a single exon 2 (wild type [WT] mRNA) or no copies of exon 2 (Del2 mRNA). Translation of the wild-type mRNA results in entirely normal dystrophin protein, whereas translation of the Del2 mRNA via translational initiation of an internal ribosome entry sequence, or IRES) results in a highly functional isoform expressed in patients known to walk into their eighth decade.
The study is designed as an open-label trial to assess safety and obtain preliminary efficacy data. scAAV9.U7.ACCA will be delivered to the systemic circulation via peripheral limb vein.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- scAAV9.U7.ACCA
- 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.
scAAV9.U7.ACCABiological
A single dose of scAAV9.U7.ACCA will be systemically delivered via a peripheral vein injection.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (Minimal Efficacious Dose) | Experimental | The Minimal Effective Dose (MED) will be delivered. Receives: Biological: scAAV9.U7.ACCA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Unacceptable Toxicity.
Unacceptable toxicity is defined as the occurrence of two or more unexpected Grade III or higher treatment-related toxicities, as defined by CTCAE 5.0.
Measured: 2 years
Secondary outcomes (3)
Change in Dystrophin Expression From Baseline Following Treatment With scAAV9.U7.ACCA.
Expression of dystrophin will be measured by immunofluorescent (IF) staining in muscle biopsies taken before and after gene therapy. This method allows for visualization of the protein and its proper location in the muscle fiber in comparison to normal protein expression.
Measured: 1 year
Change in Dystrophin Expression From Baseline Following Treatment With scAAV9.U7.ACCA.
Expression of dystrophin will be quantified by western blotting in muscle biopsies taken before and after gene therapy. This method allows for quantification of the protein amount in comparison to normal protein expression amounts.
Measured: 1 year
Changes in Percent of Exon 2 Skipping/Exclusion in the Dystrophin mRNA Transcript.
Exon 2 exclusion will be measured using RT-PCR analysis.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2020
- Study start15 Jan 2020
- Primary completion13 Nov 2023
- Study completion1 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This trial will deliver the minimal efficacious dose as determined by preclinical studies and approved by the FDA to determine safety and target engagement.
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Megan Waldrop
- Sponsor type
- University, hospital or other
- Collaborators
- Audentes Therapeutics, Astellas Pharma Inc
- Responsible party
- Sponsor-investigator, Megan Waldrop, Nationwide Children's Hospital
- Investigators
- Megan Waldrop, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04240314
- Sponsor's protocol ID
- AAV9 Dup2 U7
- Status last verified
- Aug 2025
- First submitted
- 22 Jan 2020
- Last updated
- 11 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Wein N, Vulin A, Falzarano MS, Szigyarto CA, Maiti B, Findlay A, Heller KN, Uhlen M, Bakthavachalu B, Messina S, Vita G, Passarelli C, Brioschi S, Bovolenta M, Neri M, Gualandi F, Wilton SD, Rodino-Klapac LR, Yang L, Dunn DM, Schoenberg DR, Weiss RB, Howard MT, Ferlini A, Flanigan KM. Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice. Nat Med. 2014 Sep;20(9):992-1000. doi: 10.1038/nm.3628. Epub 2014 Aug 10.
PubMed 25108525Vulin A, Wein N, Simmons TR, Rutherford AM, Findlay AR, Yurkoski JA, Kaminoh Y, Flanigan KM. The first exon duplication mouse model of Duchenne muscular dystrophy: A tool for therapeutic development. Neuromuscul Disord. 2015 Nov;25(11):827-34. doi: 10.1016/j.nmd.2015.08.005. Epub 2015 Aug 11.
PubMed 26365037Gurvich OL, Maiti B, Weiss RB, Aggarwal G, Howard MT, Flanigan KM. DMD exon 1 truncating point mutations: amelioration of phenotype by alternative translation initiation in exon 6. Hum Mutat. 2009 Apr;30(4):633-40. doi: 10.1002/humu.20913.
PubMed 19206170Flanigan KM, Dunn DM, von Niederhausern A, Howard MT, Mendell J, Connolly A, Saunders C, Modrcin A, Dasouki M, Comi GP, Del Bo R, Pickart A, Jacobson R, Finkel R, Medne L, Weiss RB. DMD Trp3X nonsense mutation associated with a founder effect in North American families with mild Becker muscular dystrophy. Neuromuscul Disord. 2009 Nov;19(11):743-8. doi: 10.1016/j.nmd.2009.08.010. Epub 2009 Sep 29.
PubMed 19793655Vulin A, Barthelemy I, Goyenvalle A, Thibaud JL, Beley C, Griffith G, Benchaouir R, le Hir M, Unterfinger Y, Lorain S, Dreyfus P, Voit T, Carlier P, Blot S, Garcia L. Muscle function recovery in golden retriever muscular dystrophy after AAV1-U7 exon skipping. Mol Ther. 2012 Nov;20(11):2120-33. doi: 10.1038/mt.2012.181. Epub 2012 Sep 11.
PubMed 22968479
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/IIa Systemic Gene Delivery Clinical Trial of scAAV9.U7.ACCA for Exon 2 Duplication-Associated Duchenne Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT04240314
- Acronym / sponsor ID
- AAV9 Dup2 U7
- Conditions
- Duchenne Muscular Dystrophy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Megan WaldropUniversity, hospital or other
- Collaborators
- Audentes Therapeutics, Astellas Pharma Inc
- Study start
- 15 Jan 2020 (actual)
- Primary completion
- 13 Nov 2023 (actual)
- Study completion
- 1 Jul 2025 (actual)
- First posted
- 27 Jan 2020 (actual)
- Results
- Posted 11 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Open-label, single dose clinical trial of scAAV9.U7.ACCA via peripheral limb vein injection for Duchenne muscular dystrophy boys who have a duplication of exon 2.
Detailed description
The proposed clinical trial is a systemic (intravenous) delivery of scAAV9.U7.ACCA for DMD patients with a duplication of exon 2 in the DMD gene. Preclinical data shows that the small nuclear RNA (snRNA) construct delivered by the scAAV9.U7.ACCA vector causes significant skipping of exon 2, resulting in exclusion of the exon from the mature messenger RNA (mRNA) with a high degree of efficiency, leading to mRNA containing only a single exon 2 (wild type [WT] mRNA) or no copies of exon 2 (Del2 mRNA). Translation of the wild-type mRNA results in entirely normal dystrophin protein, whereas translation of the Del2 mRNA via translational initiation of an internal ribosome entry sequence, or IRES) results in a highly functional isoform expressed in patients known to walk into their eighth decade.
The study is designed as an open-label trial to assess safety and obtain preliminary efficacy data. scAAV9.U7.ACCA will be delivered to the systemic circulation via peripheral limb vein.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This trial will deliver the minimal efficacious dose as determined by preclinical studies and approved by the FDA to determine safety and target engagement.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (Minimal Efficacious Dose) | Experimental | Biological: scAAV9.U7.ACCAThe Minimal Effective Dose (MED) will be delivered. |
Who may qualify
- Ages
- 6 months to 13 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Age greater than 6 months and less than 14 years
- Confirmed duplication of exon 2 in the DMD gene using a clinically accepted technique that completely defines the mutation
- Pre-ambulant (not yet walking) or ambulant (as defined by the ability to walk 10 meters without assistance)
- Males of any ethnic group will be eligible
- Ability to cooperate with muscle testing
Key exclusion criteria (10 listed)
- Active viral infection based on clinical observations
- Symptoms or signs of cardiomyopathy, including:
- 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
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 |
|---|---|---|
| scAAV9.U7.ACCAA single dose of scAAV9.U7.ACCA will be systemically delivered via a peripheral vein injection. | Biological | Cohort 1 (Minimal Efficacious Dose) |
Primary outcome
Number of Participants With Unacceptable Toxicity.
Time frame: 2 years
Unacceptable toxicity is defined as the occurrence of two or more unexpected Grade III or higher treatment-related toxicities, as defined by CTCAE 5.0.
3 secondary outcomes
Change in Dystrophin Expression From Baseline Following Treatment With scAAV9.U7.ACCA.
Time frame: 1 year
Change in Dystrophin Expression From Baseline Following Treatment With scAAV9.U7.ACCA.
Time frame: 1 year
Changes in Percent of Exon 2 Skipping/Exclusion in the Dystrophin mRNA Transcript.
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25108525Wein N, Vulin A, Falzarano MS, Szigyarto CA, Maiti B, Findlay A, Heller KN, Uhlen M, Bakthavachalu B, Messina S, Vita G, Passarelli C, Brioschi S, Bovolenta M, Neri M, Gualandi F, Wilton SD, Rodino-Klapac LR, Yang L, Dunn DM, Schoenberg DR, Weiss RB, Howard MT, Ferlini A, Flanigan KM. Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice. Nat Med. 2014 Sep;20(9):992-1000. doi: 10.1038/nm.3628. Epub 2014 Aug 10.
- Background: PubMed 26365037Vulin A, Wein N, Simmons TR, Rutherford AM, Findlay AR, Yurkoski JA, Kaminoh Y, Flanigan KM. The first exon duplication mouse model of Duchenne muscular dystrophy: A tool for therapeutic development. Neuromuscul Disord. 2015 Nov;25(11):827-34. doi: 10.1016/j.nmd.2015.08.005. Epub 2015 Aug 11.
- Background: PubMed 19206170Gurvich OL, Maiti B, Weiss RB, Aggarwal G, Howard MT, Flanigan KM. DMD exon 1 truncating point mutations: amelioration of phenotype by alternative translation initiation in exon 6. Hum Mutat. 2009 Apr;30(4):633-40. doi: 10.1002/humu.20913.
- Background: PubMed 19793655Flanigan KM, Dunn DM, von Niederhausern A, Howard MT, Mendell J, Connolly A, Saunders C, Modrcin A, Dasouki M, Comi GP, Del Bo R, Pickart A, Jacobson R, Finkel R, Medne L, Weiss RB. DMD Trp3X nonsense mutation associated with a founder effect in North American families with mild Becker muscular dystrophy. Neuromuscul Disord. 2009 Nov;19(11):743-8. doi: 10.1016/j.nmd.2009.08.010. Epub 2009 Sep 29.
- Background: PubMed 22968479Vulin A, Barthelemy I, Goyenvalle A, Thibaud JL, Beley C, Griffith G, Benchaouir R, le Hir M, Unterfinger Y, Lorain S, Dreyfus P, Voit T, Carlier P, Blot S, Garcia L. Muscle function recovery in golden retriever muscular dystrophy after AAV1-U7 exon skipping. Mol Ther. 2012 Nov;20(11):2120-33. doi: 10.1038/mt.2012.181. Epub 2012 Sep 11.
Related trials for Duchenne Muscular Dystrophy
RecruitingEarly Phase 1
Safety and Dystrophin Expression of SPOT-03 in Duchenne Muscular Dystrophy (DMD) Patients
Duchenne Muscular Dystrophy (DMD)
RecruitingPhase 2
Safety and Efficacy of KER-065 in Participants With Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy
Not yet recruitingPhase 2
A Phase 2 Trial to Investigate the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Tegacorat in Male Participants 4 to <7 Years of Age With Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy (DMD)
Not yet recruitingObservational study
Multimodal Study About Absence of Dp140 in Becker Muscular Dystrophy: Brain-muscle Imaging, Cognition and Muscle Function
Becker Muscular Dystrophy
Enrolling by invitationObservational study
A Long-term Observational Study Evaluating Eteplirsen, Golodirsen, or Casimersen in Routine Clinical Practice
Duchenne Muscular Dystrophy
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.
Megan Waldrop, 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 1/2 study testing scAAV9.U7.ACCA in people with Duchenne Muscular Dystrophy, run by Megan Waldrop 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 6 inclusion and 10 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 11 Sep 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 11 Sep 2025). 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 Participants With Unacceptable Toxicity. (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 NCT04240314, which also lists 5 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 11 Sep 2025.