Gene therapy GC310 for adults with Wilson's disease

Who can take part

• Aged ≥ 18 years, sex unrestricted
• Definitive diagnosis of Wilson disease (WD) based on:; (i) or (ii) + (iii) and (iv), or (i) or (ii) + (v); (i) Neurological and/or psychiatric symptoms; (ii) Unexplained liver injury; (iii) Reduced serum ceruloplasmin and/or elevated 24-hour urinary copper; (iv) Positive corneal Kayser-Fleischer (K-F) ring; (v) Biallelic pathogenic ATP7B variants confirmed by segregation analysis and variant pathogenicity assessment
• Serum ceruloplasmin concentration < ½ × lower limit of normal (LLN)
• Willing and able to comply with all study procedures, and has provided written informed consent

Who cannot take part

• Concurrent conditions that may interfere with study conduct or assessment, including significant gastrointestinal, cardiovascular, cerebrovascular, renal, endocrine, haematological, immunological, neurological or psychiatric disorders other than Wilson disease
• Vaccination within 2 weeks prior to planned dosing
• Prior exposure to any gene-therapy product
• Participation in any other clinical trial (WD-related or not) within 3 months before screening
• Renal impairment (any degree)
• Current hepatic decompensation or history of hepatic decompensation
• History of acute liver failure from any cause
• Evidence of advanced liver disease defined by either:; MELD score ≥ 12, or; Child-Pugh score ≥ 7
• Severe neuro-psychiatric manifestations that, in the investigator's opinion, could compromise subject safety or interfere with study participation
• Positive for HIV antibody, hepatitis C antibody, Treponema pallidum antibody, or hepatitis B surface antigen
• Contraindications to glucocorticoid therapy judged by the investigator (e.g., uncontrolled hypertension, systemic fungal infection, glaucoma, osteoporosis, active tuberculosis)
• History of severe hypersensitivity to foods or drugs, including recombinant proteins
• Any other condition or circumstance that, in the opinion of the investigator, renders the subject unsuitable for the study (e.g., poor compliance)
• Screening serum anti-AAV5 neutralizing antibody titre > 1:100
• Clinically significant laboratory abnormality at screening or baseline:; ALT or AST ≥ 5 × ULN, direct bilirubin > 1 × ULN, or albumin < 1 × LLN; Blood ammonia > 1 × ULN
• Subjects meeting ANY of the following criteria will be excluded:
• Liver stiffness measurement (LSM) ≥ 15 kPa by transient elastography at screening
• Pregnant or lactating women
• Women of child-bearing potential or fertile men who plan to conceive within 1 year after dosing or are unwilling to use highly effective contraception
• Body-mass index ≥ 24 kg/m²