Safety and Efficacy Study of NGGT002 in PKU Adult Subjects

Early Phase 1

Recruiting

• Conditions: Phenylketonurias
• Interventions: Genetic: NGGT002

• Registration Number: NCT06061614
• Lead Sponsor: First Affiliated Hospital Bengbu Medical College

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2023-03-30
• Study First Submitted: 2023-09-25
• Study First Submitted QC: 2023-09-25
• Study First Posted: 2023-09-29
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-05
• Last Update Posted: 2024-02-07
• Primary Completion: 2028-12-30
• Study Completion: 2028-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 9

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose level 1	NGGT002	Dose level 1 will be administered
Dose level 2	NGGT002	Dose level 2 will be administered
Dose level 3	NGGT002	Dose level 3 will be administered

Primary Outcome Measures

Name	Time	Method
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)	Week 52	Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) from baseline to week 52 (W52)

Secondary Outcome Measures

Name	Time	Method
plasma Phe levels	W12, W28, W52	Change from baseline in mean plasma Phe levels

Trial Locations

Locations (1)

The First Affiliated Hospital of Bengbu Medical College; 🇨🇳 Bengbu, Anhui, China