Safety and Efficacy Study of NGGT002 in cPKU Adult Subjects

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

  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

  Week 12, Week 28, Week 52

Secondary Outcomes (4)

• 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

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）
• 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
• In the investigator's assessment, the subject 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

  First Affiliated Hospital of Bengbu Medical College

  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 25, 2024
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2031
• Last Updated: November 14, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)