Phase I/II Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of GC310 Injection in Patients With Wilson's Disease (WD)

Официальное название

A Multicenter, Open-label, Single-dose, Dose-escalation Phase I/II Clinical Trial Evaluating the Safety, Tolerability, and Efficacy of GC310 Adeno-associated Virus Injection in the Treatment of Patients With Wilson's Disease (WD)

Обзор

The goal of this clinical trial is to learn if GC310 (AAV5-ATP7B) gene therapy can treat Wilson's Disease (WD) in patients over the age of 18 years old. The main questions it aims to answer are: Is GC310 safe and tolerable to WD patients? What is the recommended phase II dose (RP2D)? What is the change from baseline in 24-hour urinary copper concentration after 52 weeks of administration? Participants will be administrated GC310 intravenously and be followed up for 52 weeks to observe drug safety, tolerability and efficacy .

Вмешательства

• Генная терапия GC310
  GC310 is an adeno-associated virus 5 (AAV5) vector delivering a functional copy of the truncated human ATP7B gene

Первичные конечные точки

• Incidence of adverse events after GC310 administration [Срок оценки: within 12 weeks]
• Incidence of dose-limiting toxicity (DLT) events after GC310 administration; [Срок оценки: within 4 weeks]
• Change from baseline in serum ceruloplasmin (CP) concentration after GC310 administration; [Срок оценки: 52 weeks]
• Change from baseline in 24-hour urinary copper excretion after GC310 administration. [Срок оценки: 52 weeks]

Вторичные конечные точки (8)

• Change from baseline in the urinary copper-to-creatinine ratio [Срок оценки: 52 weeks]
• Change from baseline in ALT and AST levels [Срок оценки: 52 weeks]
• Change from baseline in hepatic imaging findings [Срок оценки: 52 weeks]
• Change from baseline in Kayser-Fleischer (K-F) rings observed by slit-lamp examination [Срок оценки: 52 weeks]
• Evaluation of adverse-event incidence [Срок оценки: 52 weeks]
• Serum anti-AAV5 and anti-ATP7B antibody levels [Срок оценки: 52 weeks]
• Change in blood GC310 vector genome copy number [Срок оценки: 52 weeks]
• AAV shedding [Срок оценки: 52 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

Subjects meeting ANY of the following criteria will be excluded:

• 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.
• Renal impairment (any degree).
• Current hepatic decompensation or history of hepatic decompensation.
• Liver stiffness measurement (LSM) ≥ 15 kPa by transient elastography at screening.
• 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).
• 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.
• 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.
• History of severe hypersensitivity to foods or drugs, including recombinant proteins.
• 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.
• Any other condition or circumstance that, in the opinion of the investigator, renders the subject unsuitable for the study (e.g., poor compliance).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking Union Medical College — Пекин

Идентификаторы

NCT: NCT07173933 · JLJY-GC310-WD-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗