Evaluating NGGT002 for treating adult Phenylketonuria

A Phase I/II Study for the Safety and Efficacy of Intravenous Infusion With NGGT002 in Adults Patients With Classic Phenylketonuria

This study is testing a new gene therapy called NGGT002 to see if it can safely help adults with classic Phenylketonuria lower their blood phenylalanine levels.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: NGGT (Suzhou) Biotechnology Co., Ltd. (Industry-sponsored)
• Locations: 2 sites (Bengbu, Anhui and 1 other locations)
• Trial ID: NCT06687733 on ClinicalTrials.gov

What this trial studies

This study is a Phase 1/2, open-label, multi-center trial aimed at assessing the safety and efficacy of NGGT002, a gene therapy product, in adult patients with classic Phenylketonuria (PKU). Participants will receive a single intravenous infusion of NGGT002, which contains a functional copy of the PAH gene, and will be monitored for safety and efficacy over a period of five years. The study includes multiple dose cohorts to determine the optimal dosage and its effects on blood phenylalanine levels.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 55 with biallelic pathogenic variants in the PAH gene and poorly controlled phenylalanine levels.

Not a fit: Patients whose PKU is well-controlled with existing therapies or those with anti-AAV8 neutralizing antibodies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve metabolic control and quality of life for adults with classic PKU.

How similar studies have performed: While gene therapy approaches for PKU are emerging, this specific application of NGGT002 is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily participating in the study and signing the informed consent form;
2. Gender is not limited; patients must carry biallelic pathogenic or likely pathogenic variants in the PAH gene;
3. Adult patients aged 18 to 55 years;
4. 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;
5. Willing and able to manage their diet;
6. According to the investigator's opinion, willing and able to comply with the study procedures and requirements;
7. 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:

1. Presence of anti-AAV8 neutralizing antibodies（≥1:5）
2. Subjects whose disease is well-controlled with existing therapies, such as those currently receiving medications like Sapropterin Dihydrochloride tablets, Pegvaliase-pqpz, etc.;
3. 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
4. At screening, clinically significant abnormal vital signs, physical examination, laboratory test results, or other relevant findings that, in the investigator's opinion, make the subject unsuitable for inclusion;
5. In the investigator's assessment, the subject has contraindications to corticosteroid use or conditions that could lead to a worsening of the condition;
6. Hepatitis A virus infection, active or occult hepatitis B virus infection, active hepatitis C virus infection, positive for Human Immunodeficiency Virus (HIV) antibodies, positive syphilis test, active or latent tuberculosis (TB) infection;
7. A significant history of liver disease, such as steatosis, fibrosis, non-alcoholic steatohepatitis, and cirrhosis, biliary diseases, within 6 months prior to signing the informed consent form, except for Gilbert's syndrome;
8. History of malignant tumors;
9. Imaging (liver ultrasound) evidence of severe liver diseases such as hepatic fibrosis or cirrhosis;
10. In the investigator's assessment, the subject has a history of serious cardiovascular, respiratory, gastrointestinal, endocrine, renal, hematological, neurological, psychiatric, or other systemic diseases before screening;
11. History of allergy to human serum albumin;
12. Subjects with a history of substance abuse (e.g., alcohol, heroin, amphetamines, etc.);
13. Subjects who have received gene therapy at any time in the past.
14. Subjects who have participated in other non-gene therapy drug clinical trials and received the investigational drug within 3 months (or 5 half-lives of the other investigational drug) prior to screening;
15. Subjects with elevated Alpha-fetoprotein (AFP);
16. Other conditions that, in the investigator's opinion, make the subject unsuitable for inclusion, such as severe comorbidities associated with PKU (e.g., renal insufficiency or renal failure, osteoporosis, anemia, gastroesophageal reflux or peptic ulcer, major depressive disorder, epilepsy, etc.);
17. Subjects weighing more than 100 kg;
18. Subjects whose daily diet includes excessive natural protein intake (\>2 g/kg/day).

Where this trial is running

Bengbu, Anhui and 1 other locations

• First Affiliated Hospital of Bengbu Medical College — Bengbu, Anhui, China (Recruiting)
• Xinhua Hospital Affifiated to Shanghai Jiao Tong University School of Medicine — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Jianping Weng, PhD — First Affiliated Hospital of Bengbu Medical College
• Study coordinator: Huan Zhou, PhD

Conditions Phenylketonurias