A Clinical Study for the Safety and Efficacy of IV Infusion of NGGT002 in the Treatment of Phenylketonuria

The First Affiliated Hospital of Bengbu Medical University1 个研究点分布在 1 个国家目标入组 15 人开始时间: 2023年3月30日最近更新: 2026年8月6日

适应症

干预措施

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方
入组人数: 15
试验地点: 1
主要终点: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a single-center, open-label, non-randomized, dose escalation study to evaluate the safety, tolerability and efficacy of NGGT002 in adult Phenylketonuria (PKU) subjects. All subjects will receive a single administration of NGGT002 and will be followed for safety and efficacy for 5 years.

详细描述

This study is designed to evaluate the safety and efficacy of NGGT002 gene therapy in adult subjects diagnosis with PKU due to confirmed PAH gene mutations indicative of PAH deficiency. NGGT002 will be administered via intravenous infusion. The study will begin with Dose Level 1, followed by a stepwise dose escalation. After evaluating the safety and efficacy data, a decision will be made to either expand the current cohort or proceed to the next dose level. The same process will be followed for subsequent dose cohorts.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Sequential
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Voluntarily sign informed consent form;
•Male and female subjects with diagnosis of PKU caused by confirmed phenylalanine hydroxylase(PAH) mutation according to the "Clinical Practice Guidelines for Phenylketonuria, 2020 Edition";
•Age ≥ 18 years;
•Blood phenylalanine (Phe) concentration ≥ 600 μmol/L at least once within 2 years prior to screening, with one measurement confirmed within six months of enrollment;
•Subjects are able to maintain their baseline diet throughout the study (regardless of dietary phenylalanine restriction), and willingness to follow the instruction of investigators to manage the diet for the duration of the trial;
•Subjects are required to obtain approval from the investigator prior to the use of any concomitant medications during the study period;
•Willingness and capable per Investigator opinion to comply with study procedures and requirements;
•Female participants of childbearing potential must have abstained from unprotected sexual intercourse for at least 14 days prior to dosing, and must have a documented negative serum hCG test between Day -7 and Day
•All participants must be willing to use a highly effective method of contraception for at least 12 months following NGGT002.

排除标准

•Anti-AAV8 neutralizing antibody>1:10
•Prior gene therapy
•Positive hepatitis B virus surface antigen, hepatitis C virus antibody, anti-human immunodeficiency virus antibody or treponema pallidum-specific antibody
•Hepatic function abnormal: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 × ULN; alkaline phosphatase (ALP) > 1.5 × ULN; total bilirubin (TBil) > 1.5 × ULN; international normalized ratio (INR) > 1.3
•Serum creatinine(Scr)> 1.5 × ULN
•Hematology values outside of the normal range (Hemoglobin < 110 g/L (male), < 100 g/L (female), white blood cells < 3.0 × 10^9/L, neutrophils < 1.5 × 10^9/L, platelet counts < 100 × 10^9/L;
•Hemoglobin A1c > 6%, or fasting glucose > 6.1 mmol/L;
•Clinically significant abnormalities in vital signs, physical examination findings, laboratory tests, or other assessments that, in the Investigator's judgment, are deemed unsuitable for study enrollment;
•Any contraindications to corticosteroid use or conditions potentially worsened by corticosteroids, as assessed by the Investigator, including but not limited to hypersensitivity to glucocorticoids, epilepsy, recent or unresolved bone fractures, ongoing wound healing, uncontrolled infections, or clinically significant osteoporosis;
•Subjects with a history of allergy to human serum albumin;
•All types of past and current malignancy;
•Severe diseases in the cardiovascular, respiratory, digestive tract, endocrine, kidney, blood, nervous, mental and other systems before screening;
•Subjects with history of live diseases, such as hepatitis, liver cirrhosis, liver cancer or other serious liver diseases;
•Subjects who participated in other clinical trails and took drugs within 3 months before screening;
•Other conditions that the Investigators deemed inappropriate for enrollment.