AAV9 U7snRNA Gene Therapy to Treat Boys With DMD Exon 2 Duplications.
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|ClinicalTrials.gov Identifier: NCT04240314|
Recruitment Status : Enrolling by invitation
First Posted : January 27, 2020
Last Update Posted : January 27, 2020
|Condition or disease||Intervention/treatment||Phase|
|Duchenne Muscular Dystrophy||Biological: scAAV9.U7.ACCA||Phase 1 Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||3 participants|
|Intervention Model:||Single Group Assignment|
|Intervention 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)|
|Official Title:||Phase I/IIa Systemic Gene Delivery Clinical Trial of scAAV9.U7.ACCA for Exon 2 Duplication-Associated Duchenne Muscular Dystrophy|
|Actual Study Start Date :||January 15, 2020|
|Estimated Primary Completion Date :||January 15, 2023|
|Estimated Study Completion Date :||January 15, 2025|
Experimental: Cohort 1 (Minimal Efficacious Dose)
The Minimal Effective Dose (MED) will be delivered.
A single dose of scAAV9.U7.ACCA will be systemically delivered via a peripheral vein injection.
- Monitoring for the development of 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.
- Change in dystrophin expression from baseline following treatment with scAAV9.U7.ACCA. [ Time Frame: 1 year ]Expression of dystrophin will be measured by immunofluorescent staining in muscle biopsies taken before and after gene therapy.
- Change in dystrophin expression from baseline following treatment with scAAV9.U7.ACCA. [ Time Frame: 1 year ]Expression of dystrophin will be quantified by western blotting in muscle biopsies taken before and after gene therapy.
- Changes in exon 2 inclusion in the dystrophin mRNA transcript. [ Time Frame: 1 year ]Exon 2 inclusion will be measured using RT-PCR analysis.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04240314
|United States, Ohio|
|Nationwide Children's Hospital|
|Columbus, Ohio, United States, 43205|
|Principal Investigator:||Megan Waldrop, MD||Nationwide Children's Hospital|