AAV8 Gene Therapy in PKU Adult Subjects

Study Overview
=================
Brief Summary
-----------------
This is a open-label, dose escalation study in adult PKU particpants.

Detailed Description
-----------------
This is a investigator initated trial which is an open-label, dose escalation study to evaluate the safety, tolerability of NGGT002 in adult PKU subjects with PAH deficiency. All Participants will only receive one administration of NGGT002 and will be followed for safety and efficacy up to five years.

Official Title
-----------------
A Clinical Study for the Safety and Efficacy of IV Infusion of NGGT002 in the Treatment of Phenylketonuria

Conditions
-----------------
Phenylketonurias

Intervention / Treatment
-----------------
* Genetic: NGGT002


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: single group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose level 1<br>Dose level 1 will be administered | Genetic: NGGT002<br>* NGGT002<br>|
| Experimental: Dose level 2<br>Dose level 2 will be administered | Genetic: NGGT002<br>* NGGT002<br>|
| Experimental: Dose level 3<br>Dose level 3 will be administered | Genetic: NGGT002<br>* NGGT002<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) | Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) from baseline to week 52 (W52) | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma Phe levels | Change from baseline in mean plasma Phe levels | W12, W28, W52 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PAH Deficiency