The primary objective of this study is to evaluate the safety and and tolerability of SPOT-mRNA03 administered by intravenous (IV) infusion to DMD patients. In addition, this study will preliminarily investigate the concentration changes in dystrophin mRNA concentration, dystrophin protein expression and engraftment, as well as cytokine profiles and immunogenicity.
This is a FIH, open-label, single-arm, and single-center exploratory clinical study of SPOT-mRNA03 administered via IV infusion for DMD patients. SPOT-mRNA03 is a muscle-targeted extracellular vesicles (EVs) loaded with full-length dystrophin mRNA. The targeting ability of SPOT-mRNA03 is conferred by molecular targeting peptides on the EVs membrane, enabling the delivery of dystrophin mRNA as a gene therapy product for DMD. The study has two ascending dose cohorts, 5.0 × 10\^9 CN dystrophin mRNA / kg and 5.0 × 10\^10 CN dystrophin mRNA / kg. The study will have a screening period of 30 days, during which patients or their legal guardian written informed consent will be obtained before screening assessments and eligibility will be determined. A total of 6 eligible subjects will participate in the study with 3 subjects in each dose cohort \[No previous treatment with corticosteroids\]. All subjects started taking 0.05-0.1mg/kg (adjusted according to the actual clinical situation) tacrolimus or sirolimus orally once daily at D-3 (3 days before initial dose of SPOT-mRNA03) for 4 weeks. All subjects are first administered via intravenous infusion on D1 and then administered twice a week (once every 4 days) for a total of 8 doses. Four weeks after the initial administration of the subjects in the previous dose cohort, if there are no serious adverse events related to the treatment, it will be determined that the subjects in next dose cohort could be administered after discussion between the investigators and the sponsor. Safety evaluations on subjects are conducted during each administration and follow-up.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
mRNA therapy delivered by extracellular vesicles (EVs)
Shanghai Children's Medical Center
Shanghai, Shanghai Municipality, China
RECRUITINGNumber of Participants with Treatment-Related Adverse Events Following Intravenous (IV) Infusion of SPOT-mRNA03 in DMD patients
Safety and tolerability of SPOT-mRNA03 will be assessed by collection and quantification of all adverse events, graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: From enrollment through 6 months post-treatment
Concentration of Dystrophin mRNA in Serum
Dystrophin mRNA concentration measured in serum of DMD patients before and after IV infusion of SPOT-mRNA03. Quantification is performed by qPCR.
Time frame: 16 weeks
Concentration of Dystrophin mRNA in Muscles
Dystrophin mRNA concentration measured in muscles of DMD patients at baseline and after the last IV infusion (dose 8) of SPOT-mRNA03. Quantification is performed by qPCR.
Time frame: 4 weeks
Percent of Normal Dystrophin Protein Expression in Muscles
Dystrophin protein measured in muscles of DMD patients at baseline and after the last IV infusion (dose 8) of SPOT-mRNA03, expressed as percent of the mean wild-type level in healthy individuals without DMD or Becker muscular dystrophy. Quantification is performed by Western Blot.
Time frame: 4 weeks
Percentage of Dystrophin-Positive Fibers in Muscles
Fiber intensity and dystrophin-positive fibers measured in muscles of DMD patients at baseline and after the last IV infusion (dose 8) of SPOT-mRNA03. Quantification is performed by Immunohistochemistry (IHC).
Time frame: 4 weeks
Concentration of Cytokines in Serum
Immunogenicity assessment will be measured by evaluating the changes of cytokines levels (TNF-α, INF-γ, IL-2, IL-6, and IL-10) in the serum of DMD patients before and after IV infusion of SPOT-mRNA03. Quantification is performed by enzyme-linked immunosorbent assay (ELISA).
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Enrollment
6
Time frame: 28 weeks
Concentration of Anti-Dystrophin Antibody in Serum
Anti-dystrophin antibody concentration measured in the serum of DMD patients before and after IV infusion of SPOT-mRNA03. Quantification is performed by enzyme-linked immunosorbent assay (ELISA).
Time frame: 28 weeks