A Phase I/II Study for the Safety and Efficacy of Intravenous Infusion With NGGT002 in Adults Patients With Classic Phenylketonuria
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Phenylketonurias
- Sponsor
- NGGT (Suzhou) Biotechnology Co., Ltd.
- Enrollment
- 18
- Locations
- 2
- Primary Endpoint
- Incidence and severity of Adverse Events (AEs)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 1/2, open-label, multiple-center, dose escalation and cohort expansion study to evaluate the safety and efficacy of NGGT002 in adult subjects with classic Phenylketonuria (PKU). NGGT002 is a rAAV8 based vector carrying a functional copy of the human PAH gene.
Participants will receive a single administration of NGGT002 and will be followed for safety and efficacy for 5 years.
Detailed Description
This study will evaluate the safety and efficacy of NGGT002 gene therapy with three dose cohorts in adult subjects with a diagnosis of classic PKU, a condition characterized by severe PAH deficiency with no residual enzyme activity. NGGT002 will be administered through intravenous infusion.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Voluntarily participating in the study and signing the informed consent form;
- •Gender is not limited; patients must carry biallelic pathogenic or likely pathogenic variants in the PAH gene;
- •Adult patients aged 18 to 55 years;
- •In the past 24 months, at least two blood Phe concentrations have been ≥600 μmol/L (10 mg/dL), with at least one of these measurements taken within 6 months prior to the screening period;
- •Willing and able to manage their diet;
- •According to the investigator's opinion, willing and able to comply with the study procedures and requirements;
- •Women of childbearing potential must have a negative serum HCG test within 7 days before dosing. Participants must agree to use highly effective contraceptive measures for at least one year after receiving NGGT002.
Exclusion Criteria
- •Presence of anti-AAV8 neutralizing antibodies（≥1:5）
- •Subjects whose disease is well-controlled with existing therapies, such as those currently receiving medications like Sapropterin Dihydrochloride tablets, Pegvaliase-pqpz, etc.;
- •Before dosing, the patient's hematological laboratory tests exceed any of the following limits:
- •Alanine Transaminase (ALT) \> 1.5×ULN and/or Aspartate Aminotransferase (AST) \> 1.5×ULN
- •Alkaline Phosphatase (ALP) \> 1.5×ULN
- •Total Bilirubin (TBil) \> 1.5×ULN, Direct Bilirubin \> 1.5×ULN
- •International Normalized Ratio (INR) \> 1.5
- •Serum Creatinine (Scr) \> 1.5×ULN
- •Hematological values outside the normal range (Hemoglobin: \<110 g/L for males, \<100 g/L for females, White Blood Cells \<3.0×10\^9/L, Neutrophils \<1.5×10\^9/L, Platelets \<100×10\^9/L)
- •Glycated Hemoglobin (HbA1c) \> 6% or Fasting Blood Glucose \> 6.1 mmol/L
Outcomes
Primary Outcomes
Incidence and severity of Adverse Events (AEs)
Time Frame: Baseline to Week 52
Incidence and severity of AEs, including serious AEs (SAEs) as assessed by CTCAE v5.0 of a single administration of NGGT002.
Change from baseline in average Plasma Phe Concentration
Time Frame: Week 12, Week 28, Week 52
To evaluate the efficacy in change of average plasma Phe concentration of IV infusion of NGGT002 in adults with classic PKU at Week 12, Week 28, Week 52
Secondary Outcomes
- Incidence of sustained plasma Phe concentration of ≤360 μmol/L (6 mg/dL) at Week 12, Week 28, Week 52 post dose(Week 12, Week 28, Week 52)
- Occurred Day to first reach Phe ≤ 360 μmol/L and the duration（days） of Phe ≤ 360 μmol/L in each dose group following NGGT002 administration(Week 52)
- Change from baseline in Phe and total protein intake at Week 28, Week 52 post dose(Week 28, Week 52)
- Score change in Phenylketonuria Quality of Life Questionnaire (PKU-QOL)(Week 28, Week 52)