Safety and Efficacy Study of NGGT002 in PKU Adult Subjects

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

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.

Study Overview

• Status: Recruiting
• Conditions: Phenylketonurias
• Intervention / Treatment: Genetic: NGGT002

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 Type: Interventional
• Enrollment (Estimated): 9
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Huan Zhou, Doctor; Phone Number: 008613665527160; Email: zhouhuanbest@vip.163.com
• Study Contact Backup: Name: Xiaoli Li, Master; Phone Number: 008615215520890; Email: 158169847@qq.com

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233000
      • Recruiting
      • The First Affiliated Hospital of Bengbu Medical College
      • Contact: Huan Zhou; Phone Number: +8613665527160; Email: zhouhuanbest@vip.163.com
      • Contact: Xiaoli Li; Phone Number: +8615215520890; Email: 158169847@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose level 1; Dose level 1 will be administered	Genetic: NGGT002; NGGT002
Experimental: Dose level 2; Dose level 2 will be administered	Genetic: NGGT002; NGGT002
Experimental: Dose level 3; Dose level 3 will be administered	Genetic: NGGT002; NGGT002

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
total protein intake	Change from baseline in total protein intake	W12, W28, W52

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Bengbu Medical College

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2023
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: September 25, 2023
• First Submitted That Met QC Criteria: September 25, 2023
• First Posted (Actual): September 29, 2023

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: PAH Deficiency
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Phenylketonurias
• Other Study ID Numbers: NGGT002-P-2202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No