Safety and Dystrophin Expression of SPOT-03 in Duchenne Muscular Dystrophy (DMD) Patients

Prior treatment

• Hospitalization for respiratory failure within 8 weeks prior to screening.
• Severe uncontrolled heart failure (NYHA III-IV), including any of the following conditions：
  • Intravenous administration of diuretics or positive inotropic drugs is required within 8 weeks prior to screening.
  • Hospitalization due to worsening heart failure or arrhythmia within 8 weeks prior to screening.
• Subjects who are undergoing immunosuppressive therapy.
• Has used other gene therapy, investigational drugs, or any treatment aimed at increasing dystrophin expression.
• Subjects with a history of major surgeries within 12 weeks prior to the initial infusion or planning to undergo major surgeries (such as scoliosis surgery) during this study.
• Subjects who are allergic to investigational products or local aesthetic drugs or have a history of severe allergies or genetic allergic reactions.
• Within 6 months prior to the initial infusion, the subjects are exposed to another investigational drug or have participated in an intervention clinical trial.

Other illness

• There are severe intellectual disabilities (such as severe autism, severe cognitive impairment, and severe behavioral disorders) that, according to the investigator's judgment, can affect the study.
• Asthma or underlying lung diseases that are poorly controlled, such as bronchitis, bronchiectasis, emphysema, or recurrent infectious pneumonia that investigator believes may affect respiratory function.
• Arrhythmias that require anti-arrhythmic treatment.
• Subjects with positive hepatitis B core antibody or hepatitis C antibody or HIV antibody during screening.
• Investigator believes that the presence of any other serious diseases, medical conditions, or chronic drug treatment needs can pose unnecessary risks to gene transfer.

Lab values

• Abnormal laboratory values considered clinically significant:
  • GGT \> 3 × upper limit of normal
  • Bilirubin ≥ 3.0 mg/dL
  • Creatinine ≥ 1.8 mg/dL
  • Hemoglobin \< 8 or \> 18 g/dL
  • White blood cell count \> 18,500/μL

Other

• Complications other than DMD that may cause muscle weakness and/or motor dysfunction.

• According to the requirements of the region/country and/or IRB/IEC, the patient and/or legal guardian have signed a written informed consent form and are aware of all relevant study content.
• Boys aged ≥ 2 years to \< 8 years and capable of walking independently for at least 10 meters.
• The medical history includes clinical diagnosis of DMD and confirmed Duchenne mutations using validated genetic testing (MLPA and whole genome sequencing).
• Able to tolerate muscle biopsy under anesthesia and have no contraindications to biopsy.
• Heart, liver, lung, and kidney functions are sufficient:
  • The left ventricular ejection fraction (LVEF) should be ≥ 50%;
  • Forced vital capacity (FVC) \> 50% of the expected value, and do not require nighttime ventilation;
  • Patient's glomerular filtration rate (GFR)\>30 mL/min/1.73 m2