Clinical Trial to Evaluate the Safety and Efficacy of EXG001-307 in Patients With Spinal Muscular Atrophy Type I

The purpose of this study was to evaluate the safety and preliminary efficacy of a single intravenous injection of exg001-307 in patients with type I spinal muscular atrophy.

The research process includes the screening period (the screening period is from the time the subject signs the informed consent to the time before hormone pretreatment, with a maximum of 28 days), the treatment period (the subject receives hospitalization and observation including hormone pretreatment and single infusion of study drugs), and the follow-up period (the end of the treatment period until the subject reaches the age of 18 months, loss of follow-up, active withdrawal from the study or death). The qualified subjects in the screening period enter the treatment period, receive exg001-307 treatment, and enter the follow-up period after hospitalization observation. At the end of the study visit (subjects 18 months old), eligible subjects will be asked to transfer to the long-term follow-up study.


Eligibility Criteria:
Inclusion Criteria:

1. SMA was diagnosed by bilateral allele SMN1 mutation (deletion or point mutation) gene, and there were 2 copies of SMN2 gene.
2. On the day of administration, the age of the subjects did not exceed the 180th day after birth.
3. The clinical history and signs are consistent with the manifestations of type I SMA, that is, hypotonia, lagging development of motor function, poor head control, round shoulder posture and excessive joint activity.
4. The legal guardian of the subject understands the purpose, possible risks and rights of the test, agrees the subject to participate in the test, completes all research steps, tests and visits, and voluntarily signs the informed consent.
5. During the study period, according to the changes of the subject's condition, the subject's legal guardian was willing to carry out standard treatment requirements such as nasal feeding, noninvasive mechanical ventilation and expectoration machine according to the researcher's suggestions.

Exclusion Criteria:

1. The gestational age at birth was less than 35 weeks (245 days).
2. During the screening period, when the subjects were awake or asleep and did not receive any auxiliary oxygen supply or respiratory support, the blood oxygen saturation was less than 96%.
3. Invasive ventilation or tracheotomy is required, or the current use of noninvasive ventilation support is ≥ 16 hours / day on average.
4. According to the WHO child growth standard (who 2009), the weight is lower than the 3rd percentile by age.
5. Before administration, if the subjects have not been vaccinated or delayed vaccination according to the national vaccination plan of the current month, it will significantly affect their safety according to the evaluation of the researcher and the medical manager of the project team;
6. Active viral infections (including HIV, covid-19, seropositive for hepatitis B or C, torch virus, EBV virus and syphilis).
7. Severe non respiratory diseases within 2 weeks before screening.
8. Upper respiratory tract infection or lower respiratory tract infection within 4 weeks before screening.
9. There are other severe infections or diseases.
10. There are known heart diseases or ECG abnormalities with clinical significance.
11. Known allergy to prednisolone, other glucocorticoids or their excipients.
12. Receive immunosuppressive therapy (e.g. cyclosporin, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab) requiring preventive administration within 3 months before administration.
13. Immunomodulatory drugs (such as thymosin, interferon, etc.) are being used to treat myopathy, neuritis and diabetes (such as immunosuppressive agents, glucocorticoids, insulin).
14. Anti AAV9 antibody titer \> 1:50 (determined by ELISA). If the potential subject's anti AAV9 antibody titer \> 1:50, it can be retested during the screening period. When the anti AAV9 antibody titer is ≤ 1:50, it can continue to participate in the screening.
15. Abnormal laboratory test values with clinical significance (GGT, ALT and AST \> 2.5) × ULN, bilirubin ≥ 3.0 mg / dl, creatinine ≥ 1.0 mg / dl, hemoglobin \< 8 or \> 18 g / dl; Leukocyte count \> 20000 / cm3; Platelet count \< 100000 / cm3).
16. Previously participated in clinical research on the treatment of other SMA drugs.
17. Major surgery was expected during study treatment.
18. Other situations that the researcher judges are not suitable to participate in this study.