Evaluating a new gene therapy for adults with Phenylketonuria

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

This study is testing a new gene therapy to see if it can safely help adults with Phenylketonuria by providing them with a missing enzyme.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Bengbu Medical University (Academic / other)
• Locations: 1 site (Bengbu, Anhui)
• Trial ID: NCT06061614 on ClinicalTrials.gov

What this trial studies

This open-label, dose escalation study aims to assess the safety, tolerability, and efficacy of NGGT002, a gene therapy product designed to express the human PAH enzyme in adults diagnosed with Phenylketonuria (PKU) due to PAH deficiency. Participants will receive a single intravenous infusion of NGGT002, with follow-up for safety and efficacy over a period of five years. The study will involve three dose cohorts, starting from a low dose and escalating based on safety and efficacy data collected throughout the trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of PKU caused by PAH mutations and elevated phenylalanine levels.

Not a fit: Patients with prior gene therapy or those with certain liver function abnormalities may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve metabolic control and quality of life for adults with PKU.

How similar studies have performed: While gene therapy for PKU is a novel approach, similar studies have shown promise in other genetic disorders, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Voluntarily sign informed consent form;
* Male and female subjects with diagnosis of PKU caused by confirmed phenylalanine hydroxylase(PAH) mutation according to the "Clinical Practice Guidelines for Phenylketonuria, 2020 Edition";
* Age ≥ 18 years;
* Blood phenylalanine (Phe) concentration ≥ 600 μmol/L at least once within 2 years prior to screening, with one measurement confirmed within six months of enrollment;
* Subjects are able to maintain their baseline diet throughout the study (regardless of dietary phenylalanine restriction), and willingness to follow the instruction of investigators to manage the diet for the duration of the trial;
* Subjects are required to obtain approval from the investigator prior to the use of any concomitant medications during the study period;
* Willingness and capable per Investigator opinion to comply with study procedures and requirements;
* Female participants of childbearing potential must have abstained from unprotected sexual intercourse for at least 14 days prior to dosing, and must have a documented negative serum hCG test between Day -7 and Day 0. All participants must be willing to use a highly effective method of contraception for at least 12 months following NGGT002.

Exclusion Criteria:

* Anti-AAV8 neutralizing antibody\>1:10
* 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
* Hematology values outside of the normal range (Hemoglobin \< 110 g/L (male), \< 100 g/L (female), white blood cells \< 3.0 × 10\^9/L, neutrophils \< 1.5 × 10\^9/L, platelet counts \< 100 × 10\^9/L;
* Hemoglobin A1c \> 6%, or fasting glucose \> 6.1 mmol/L;
* Clinically significant abnormalities in vital signs, physical examination findings, laboratory tests, or other assessments that, in the Investigator's judgment, are deemed unsuitable for study enrollment;
* Any contraindications to corticosteroid use or conditions potentially worsened by corticosteroids, as assessed by the Investigator, including but not limited to hypersensitivity to glucocorticoids, epilepsy, recent or unresolved bone fractures, ongoing wound healing, uncontrolled infections, or clinically significant osteoporosis;
* Subjects with a history of allergy to human serum albumin;
* All types of past and current malignancy;
* Severe diseases in the cardiovascular, respiratory, digestive tract, endocrine, kidney, blood, nervous, mental and other systems before screening;
* Subjects with history of live diseases, such as hepatitis, liver cirrhosis, liver cancer or other serious liver diseases;
* Subjects who participated in other clinical trails and took drugs within 3 months before screening;
* Other conditions that the Investigators deemed inappropriate for enrollment.

Where this trial is running

Bengbu, Anhui

• The First Affiliated Hospital of Bengbu Medical College — Bengbu, Anhui, China (Recruiting)

Study contacts

• Study coordinator: Huan Zhou, Doctor

Conditions Phenylketonurias; Phenylalanine hydroxylase Deficiency