Wilson disease
Conditions
Interventions
Dose Group 1 (3.0E 13 d.vg/kg):GC310 Adeno-associated Virus Injection Intravenous(3.0E+13 d.vg/kg)
Second dose group (6.0E 13 d.vg/kg):GC310 Adeno-associated Virus Injection Intravenous(6.0E+13 d.vg/kg)
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age =18 years, no gender restriction; 2. Meet the following ((1) or (2)) ((3) and (4)) or ((1) or (2)) (5) diagnostic criteria for a clear diagnosis of WD: (1) Neurological and/or psychiatric symptoms; (2) Liver damage of unknown cause; (3) Reduced serum ceruloplasmin concentration and/or increased 24-hour urinary copper; (4) Positive K-F ring in the cornea; (5) Both chromosomes of the patient carry pathogenic variants of the ATP7B gene confirmed through family co-segregation and pathogenicity analysis; 3. Serum ceruloplasmin concentration < 1/2 × LLN; 4. Willing and able to comply with all study protocol requirements and procedures, voluntarily participate, and sign the informed consent form.
Exclusion criteria
Exclusion criteria: 1. Serum anti-AAV5 neutralizing antibody >1:100 during the screening period; 2. Laboratory test abnormalities during the screening or baseline period, such as: (1) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >=5×ULN, direct bilirubin (DBil) >1×ULN, albumin 1×ULN; 3. Presence of renal insufficiency; 4. Presence of decompensated liver cirrhosis or a history of decompensated liver cirrhosis; 5. Liver stiffness measurement (LSM) >=15 KPa on liver elastography during screening; 6. History of liver failure caused by any etiology; 7. During screening, liver disease severity assessment meets any of the following: (1) MELD score >=12; (2) Child-Pugh score >=7; 8. Severe neuropsychiatric symptoms that the investigator believes could interfere with the subject’s safety or make participation inappropriate; 9. Positive for HIV antibody, HCV antibody, or syphilis antibody, or positive for hepatitis B surface antigen; 10. Investigator determines the subject has contraindications to glucocorticoid use, such as severe hypertension, systemic fungal infection, glaucoma, osteoporosis, tuberculosis, etc.; 11. Patients with other diseases that may interfere with the study or its evaluation, such as severe digestive system diseases, cardiovascular and cerebrovascular diseases, urological diseases, endocrine disorders, hematologic diseases, immune system diseases, neurological diseases, and psychiatric disorders, excluding Wilson’s disease (WD); 12. Pregnant or breastfeeding women; 13. Subjects of childbearing potential who plan to conceive within 1 year after administration or are unwilling to use effective contraception; 14. Body mass index >=24 kg/m²; 15. History of severe food or drug allergic reactions, including allergy or hypersensitivity to recombinant protein products; 16. Vaccination within less than 2 weeks before administration; 17. Prior use of gene therapy drugs; 18. Participation in other WD drug clinical trials or any clinical trial within 3 months prior to screening; 19. Investigator deems the subject unsuitable for participation, such as poor compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events within 12 weeks after administration of GC310;Incidence of DLT events within 4 weeks after GC310 administration; | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in 24-hour urinary copper over 52 weeks after GC310 administration;Change from baseline in serum ceruloplasmin (CP) concentration over 52 weeks after GC310 administration;Change from Baseline in Urinary Copper/Creatinine Ratio at 52 Weeks After GC310;Ophthalmic Slit Lamp K-F Ring Changes from Baseline 52 Weeks After GC310 Administration;Evaluate the occurrence of adverse events within 52 weeks after administration of GC31;Genomic copy number changes of GC310 vector in blood within 52 weeks after GC310 administration;Changes in ALT and AST from baseline within 52 weeks after GC310 administration;AAV shedding within 52 weeks after GC310 administration;Levels of serum anti-AAV5 and anti-ATP7B antibodies before and within 52 weeks after GC310 administration;Hepatic imaging changes from baseline at 52 weeks after GC310 administration; | — |
Countries
China
Contacts
Public ContactZhengqing Qiu
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed