SPOT-03 IV gene therapy to deliver dystrophin in boys with Duchenne muscular dystrophy

A Pilot Study for the Safety and Expression of Dystrophin in Skeletal Muscle After SPOT-03 Administration in Duchenne Muscular Dystrophy (DMD) Patients

This trial will test whether intravenous SPOT-03 is safe and increases dystrophin in ambulatory boys aged 2 to under 8 with Duchenne muscular dystrophy.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 2 Years to 7 Years
• Sex: Male
• Sponsor: Shanghai Siponuoyin Biotechnology Co Ltd (Industry-sponsored)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07188012 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, open-label, single-arm, single-center study testing muscle-targeted extracellular vesicles (SPOT-03) loaded with full-length dystrophin nucleic acid delivered by IV infusion. Six to nine ambulatory boys aged 2 to <8 will be enrolled into two dosing schedules that differ by total administrations, with concurrent oral tacrolimus to manage immune response. The primary focus is safety and tolerability, with planned measurements of dystrophin nucleic acid and protein expression from muscle biopsy, anti-dystrophin antibodies, cytokine profiles, and body composition changes. Dosing includes intensive repeat infusions and scheduled follow-up assessments to capture engraftment and biomarker changes.

Who should consider this trial

Good fit: Ambulatory boys aged 2 to less than 8 years with genetically confirmed Duchenne muscular dystrophy who can tolerate muscle biopsy and meet cardiac, pulmonary, and renal function criteria are the intended participants.

Not a fit: Nonambulatory patients, those with severe cardiac, pulmonary, or renal impairment, alternative causes of muscle weakness, or contraindications to biopsy or immunosuppression are unlikely to be eligible or benefit from this protocol.

Why it matters

Potential benefit: If successful, SPOT-03 could increase dystrophin production in muscle and potentially slow muscle degeneration and preserve function.

How similar studies have performed: AAV-based micro-dystrophin gene therapies have shown early expression and some functional signals in other trials, but EV-based delivery of full-length dystrophin like SPOT-03 is a novel and unproven approach in humans.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. Boys aged ≥ 2 years to \< 8 years and capable of walking independently for at least 10 meters.
3. The medical history includes clinical diagnosis of DMD and confirmed Duchenne mutations using validated genetic testing (MLPA and whole genome sequencing).
4. Able to tolerate muscle biopsy under anesthesia and have no contraindications to biopsy.
5. Heart, liver, lung, and kidney functions are sufficient:

   1. The left ventricular ejection fraction (LVEF) should be ≥ 50%;
   2. Forced vital capacity (FVC) \> 50% of the expected value, and do not require nighttime ventilation;
   3. Patient's glomerular filtration rate (GFR)\>30 mL/min/1.73 m2

Exclusion Criteria:

1. Complications other than DMD that may cause muscle weakness and/or motor dysfunction.
2. 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.
3. Hospitalization for respiratory failure within 8 weeks prior to screening.
4. 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.
5. Severe uncontrolled heart failure (NYHA III-IV), including any of the following conditions：

   1. Intravenous administration of diuretics or positive inotropic drugs is required within 8 weeks prior to screening.
   2. Hospitalization due to worsening heart failure or arrhythmia within 8 weeks prior to screening.
6. Abnormal laboratory values considered clinically significant:

   1. GGT \> 3 × upper limit of normal
   2. Bilirubin ≥ 3.0 mg/dL
   3. Creatinine ≥ 1.8 mg/dL
   4. Hemoglobin \< 8 or \> 18 g/dL
   5. White blood cell count \> 18,500/μL
7. Arrhythmias that require anti-arrhythmic treatment.
8. Subjects who are undergoing immunosuppressive therapy.
9. Has used other gene therapy, investigational drugs, or any treatment aimed at increasing dystrophin expression.
10. 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.
11. Subjects who are allergic to investigational products or local aesthetic drugs or have a history of severe allergies or genetic allergic reactions.
12. Within 6 months prior to the initial infusion, the subjects are exposed to another investigational drug or have participated in an intervention clinical trial.
13. Subjects with positive hepatitis B core antibody or hepatitis C antibody or HIV antibody during screening.
14. Investigator believes that the presence of any other serious diseases, medical conditions, or chronic drug treatment needs can pose unnecessary risks to gene transfer.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Children's Medical Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Wang Jiwen — Shanghai Children's Medical Center
• Study coordinator: Winston Town

Conditions Duchenne Muscular Dystrophy; North Star Ambulatory Assessment; Dystrophin; Gene Therapy; Extracellular Vesicles