Safety and Efficacy Study of NGGT002 in Adult Patients With Phenylketonuria

NCT06687733 | Recruiting Phase 1

• 1 other identifier: NGGT002-P-2302
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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.

Conditions

Phenylketonurias

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of Adverse Events (AEs)

  Incidence and severity of AEs, including serious AEs (SAEs) as assessed by CTCAE v5.0 of a single administration of NGGT002.

  Baseline to Week 52

• Change from baseline in average Plasma Phe Concentration at Weeks 12, 28 and 52.

  To evaluate the efficacy of intravenous infusion of NGGT002 in adults with classic PKU, as assessed by the change from baseline in mean plasma Phe concentration at Weeks 12, 28, and 52.

  Baseline, Week 12, Week 28, Week 52

Secondary Outcomes (4)

• Incidence of participants in each dose cohort with a plasma Phe concentration ≤360 μmol/L (6 mg/dL) at Weeks 12, 28, and 52 following NGGT002 administration.

  Week 12, Week 28, Week 52

• Time to first achievement of a plasma Phe concentration ≤360 μmol/L and duration of maintenance of plasma Phe concentration at ≤360 μmol/L in each dose cohort following NGGT002 administration.

  Week 52

• Change from baseline in daily Phe intake (mg/day) and total natural protein intake (g/day) at Weeks 28 and 52.

  Baseline, Week 28, Week 52

• Change from baseline in Phenylketonuria Quality of Life Questionnaire (PKU-QOL) score at Weeks 28 and 52.

  Baseline, Week 28, Week 52

Study Arms (1)

NGGT002

EXPERIMENTAL

Six to eighteen patients will be enrolled into three cohorts at three dose levels.

Genetic: NGGT002

Interventions

NGGT002 GENETIC

adeno-associated viral vector with human phenylalanine hydroxylase gene

NGGT002

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Presence of anti-AAV8 neutralizing antibodies（≥1:5）
• Participants whose disease is well-controlled with existing therapies, such as those currently receiving medications like Sapropterin Dihydrochloride tablets, Pegvaliase-pqpz, etc. (excluding participants who have previously received the above-mentioned drug therapies but did not respond, and have been off treatment for more than 6 weeks);
• 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
• In the investigator's assessment, the participant has contraindications to corticosteroid use or conditions that could lead to a worsening of the condition;
• 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;
• 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;
• History of malignant tumors;
• Imaging (liver ultrasound) evidence of severe liver diseases such as hepatic fibrosis or cirrhosis;

Sponsors & Collaborators

• NGGT (Suzhou) Biotechnology Co., Ltd.: lead

Study Sites (2)

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

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Jianping Weng, PhD

  The First Affiliated Hospital of Bengbu Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Huan Zhou, PhD

CONTACT

8613665527160; zhouhuanbest@vip.163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2024
• First Posted: November 14, 2024
• Study Start: July 16, 2024
• Primary Completion (Estimated): August 11, 2027
• Study Completion (Estimated): June 11, 2030
• Last Updated: August 13, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)