To Evaluate the Safety and Efficacy of GS1168 Injection in Adult Phenylketonuria

A Clinical Exploration Study of Adeno-Associated Virus Vector Expressing Human Phenylalanine Hydroxylase Gene in Adult Classical Phenylketonuria

This study is a single-arm, open-label, dose-escalation, exploratory study to evaluate the safety, tolerability, and efficacy of a single administration of GS1168 Injection in Chinese adult phenylketonuria (PKU) with PAH mutation.

Study Overview

• Status: Not yet recruiting
• Conditions: Phenylketonuria (PKU)
• Intervention / Treatment: Drug: GS1168 injection

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

Contacts and Locations

• Study Contact: Name: Yuntao Gong, MD; Phone Number: +8618910178979; Email: yuntao.gong@gritgen.com
• Study Contact Backup: Name: Sihui Pan; Phone Number: +8618105158856; Email: sihui.pan@gritgen.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • The First Affiliated Hospital of Anhui Medical University
      • Contact: Huan Zhou, PhD; Phone Number: +8613665527160; Email: zhouhuanbest@vip.163.com
      • Contact: Datong Deng, MD; Phone Number: +8613855134251; Email: 13855134251@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Understand the purpose and risks of the study and voluntarily sign Informed Consent Forms (ICF).
2. Male or female, aged 18-55 years.
3. Diagnosis of PKU due to PAH mutation, and be inadequately controlled with current therapy (e.g., dietary management) in the judgement of the investigator.
4. Intolerant of unresponsive to available treatment such as Kuvan or Palynziq, and have come off the medication for at least 28 days prior to signing the ICF.
5. Ability and willingness to maintain dietary protein intake consistent with baseline
6. Male and female subjects of childbearing potential must agree to use effective contraception methods from signing ICF until at least 52 weeks after GS1168 infusion. Female subjects must not be breastfeeding.
7. Agree to avoid alcohol consumption from 30 days prior to GS1168 infusion until at least 52 weeks after infusion.
8. Ability to communicate well with the Investigator and to understand and comply with the requirements of the study.

Exclusion Criteria:

1. Diagnosis of PKU due to other gene mutations.
2. Body weight ≥100 kg or Body Mass Index (BMI) ≥30 kg/m² at screening.
3. Presence of anti-AAV8 neutralizing antibody.

4. Abnormal liver function tests at screening:

   • ALT or AST >1.25 × Upper Limit of Normal (ULN)
   • GGT >1.25 × ULN
   • Total Bilirubin >1.5 × ULN

5. Abnormal laboratory findings at screening:

   • Hemoglobin <9 g/dL
   • Neutrophil count <1.0 × 10⁹/L
   • Platelet count <100 × 10⁹/L
   • Serum Creatinine ≥1.5 mg/dL (133 μmol/L)
   • Glycated Hemoglobin (HbA1c) >6% or Fasting Blood Glucose >6.1 mmol/L
6. Active or occult hepatitis B virus (HBV) infection, active hepatitis C virus (HCV) infection, positive Human Immunodeficiency Virus (HIV) antibodies and positive syphilis test.
7. Any severe conditions of respiratory, cardiovascular, gastrointestinal, renal, neurological, endocrine, immunological, hematological, psychiatric, etc.
8. History of malignancy.
9. Any other condition that, in the opinion of the Investigator, may affect subject compliance or render the subject unsuitable for participation in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group Arm of GS1168; Dose level 1, level 2 and level 3 will be administered	Drug: GS1168 injection; The dose levels are as follows: A single intravenous administration of GS1168 injection at dose level 1;; A single intravenous administration of GS1168 injection at dose level 2;; A single intravenous administration of GS1168 injection at dose level 3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse event (AE), including serious adverse event (SAE) and adverse event of special interest (AESI)	Incidence of adverse event (AE), including serious adverse event (SAE) and adverse event of special interest (AESI) as assessed by CTCAE V5.0, from baseline to week 52	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Phe levels	Change from baseline in plasma level of Phe following GS1168 injection administration	Week 52
Total protein intake	Change from baseline in total protein intake following GS1168 injection administration	Week 52
Phenylketonuria Quality of Life (PKU-QOL) scores	Change in Phenylketonuria Quality of Life Questionnaire (PKU-QOL, Score range: 0-100, higher scores indicate worse outcomes.)	Week 52

Collaborators and Investigators

• Sponsor: Gritgen Therapeutics Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2025
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): August 30, 2031

Study Registration Dates

• First Submitted: December 1, 2025
• First Submitted That Met QC Criteria: December 19, 2025
• First Posted (Actual): January 6, 2026

Study Record Updates

• Last Update Posted (Actual): January 6, 2026
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Phenylketonurias
• Other Study ID Numbers: GS1168-201

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