AAV Gene Therapy Clinical Study in Adult Classic PKU (PHEdom)

Exclusion Criteria

• •1. Subjects with PKU that is not due to PAH mutation
• •2. Presence of anti-AAV8 neutralizing antibodies
• •3. Prior to dosing, subjects exceed the limit of any of the following liver function and hematology tests in two consecutive blood laboratory tests:
• •* Alanine aminotransferase (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
• •* Blood creatinine (Scr) \>1.5×ULN
• •* Hematology values outside of the normal range (Hemoglobin \<110 g/L (male), \<100 g/L (female), white blood cell \<3.0×10\^9/L, neutrophil \<1.5×10\^9/L, platelet \<100×10\^9/L)
• •* Hemoglobin A1c \>6% or fasting glucose \>6.1 mmol/L
• •4. At the time of screening, abnormal vital signs (i.e. Temperature\<36.3°C or \>37.4°C; Blood pressure\<100/60 mmHg or \>130/80 mmHg; heart rate \<60/min or\>100/min; respiratory rate \<12/min or \>18/min; oxygen saturation\<95%), physical examination, laboratory tests, or other related results that have clinical significance, and the researchers believe they are unsuitable for enrollment.
• •5. Contraindications to corticosteroid use or possible deterioration of corticosteroid use assessed and determined by the Investigator.
• •6. Active infection with hepatitis A virus (HAV ribonucleic acid \[RNA\] positive), active or occult hepatitis B virus infection (positive HBV-DNA or anti-HBc positive with negative hBsAg, HBV surface antigen), active infection with hepatitis C virus (HCV RNA positive), infection with the human immunodeficiency virus (HIV) as measured by antibodies to HIV-1 and HIV-2, active or latent infection with tuberculosis (TB) measured by Quantiferon Gold, infection with syphilis by rapid plasma regainn (RPR) and/or serum syphilis antibody, treponema pallidum particle agglutination (TPPA).
• •7. Subjects with history of liver disease such as clinically significant steatosis, fibrosis, non-alcoholic steatohepatitis (NASH) and cirrhosis, biliary disease within 6 months of informed consent; except for Gilbert's syndrome.
• •8. All types of past and current malignancy
• •9. Imaging (liver ultrasound) proved the existence of Liver fibrosis, liver cirrhosis and other serious liver diseases
• •10. Severe diseases in the cardiovascular, respiratory, digestive tract, endocrine, kidney, blood, nervous, mental and other systems before screening.
• •11. History of allergy to Albumin (Human)
• •12. The subjects who have Substance Use Disorder (for example alcohol, heroin, amphetamine, etc)
• •13. The subjects who have received any gene therapy in the past, regardless of when it was administered.
• •14. The subjects who have received any investigational treatment and took drugs within 3 months before screening (or 5 half-lives, if longer)
• •15. Subjects with elevated circulating serum alpha-fetoprotein (AFP)
• •16. Other conditions that the Investigators deemed inappropriate for enrollment, such as PKU severe comorbidities and conditions (i.e. renal insufficiency or kidney failure, osteoporosis, anemia, acid reflux or gastro-esophageal ulcer, major depression, epilepsy, etc.), which may be deteriorated with the potential risks of NGGT002.
• •17. Subjects who are presently on available medications for the treatment of PKU, such as Kuvan, Palynziq, etc.
• •18. Subjects who weight over 120 Kg
• •19. Subjects who consume too much natural protein (\>2 g/Kg body weight/day) in their daily diet
• •20. Breastfeeding subjects will not be included in the study