Safety and Efficacy Study of NGGT002 in PKU Adult Subjects

First Affiliated Hospital Bengbu Medical College

Status and phase: Enrolling; Early Phase 1

Conditions: Phenylketonurias

Treatments: Genetic: NGGT002

Study type: Interventional

Funder types: Other

Identifiers

NCT06061614

NGGT002-P-2202

Details and patient eligibility

About

This investigator initiated trial is an open-label, dose escalation study to evaluate the safety, tolerability and efficacy of NGGT002, an AAV derived investigational gene therapy product expressing human PAH enzyme in adult Phenylketonuria (PKU) subjects with PAH deficiency. All participants will receive a single administration of NGGT002 and will be followed for safety and efficacy for 5 years.

Full description

This study will evaluate the safety and efficacy of NGGT002 gene therapy with three dose cohorts in adult subjects with diagnosis of PKU characterized by PAH deficiency with confirmed PAH gene mutations. NGGT002 will be administered through intravenous infusion. Dose escalation will be initiated from the low dose of NGGT002. After evaluating the safety and efficacy data, a decision will be made regarding the cohort expansion or the escalation to the next dose level. The same process will be followed for subsequent dose cohorts.

Enrollment: 9 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Voluntarily sign informed consent form;
• Male and female subjects with diagnosis of PKU caused by confirmed PAH mutation as per the "Clinical Practice Guidelines for Phenylketonuria 2020";
• Age ≥ 18 years;
• Phe concentration ≥ 600 μmol/L at screening and ≥ 600 μmol/L at least once within 2 years prior to screening;
• Subjects who are willing and able to maintain their baseline diet throughout the study, regardless of phenylalanine restriction, except at the investigator's request;

Exclusion criteria

• Presence of anti-AAV8 neutralizing antibody
• Prior gene therapy
• Positive hepatitis B virus surface antigen, hepatitis C virus antibody, anti-human immunodeficiency virus antibody or treponema pallidum-specific antibody
• Hepatic function abnormal: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 × ULN; alkaline phosphatase (ALP) > 1.5 × ULN; total bilirubin (TBil) > 1.5 × ULN; international normalized ratio (INR) > 1.3

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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9 participants in 3 patient groups

Dose level 1

Experimental group

Description:

Dose level 1 will be administered

Treatment:

Genetic: NGGT002

Dose level 2

Experimental group

Description:

Dose level 2 will be administered

Treatment:

Genetic: NGGT002

Dose level 3

Experimental group

Description:

Dose level 3 will be administered

Treatment:

Genetic: NGGT002