Phenylketonuria (PKU)
Conditions
Brief summary
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.
Interventions
DRUGGS1168 injection
The dose levels are as follows: 1. A single intravenous administration of GS1168 injection at dose level 1; 2. A single intravenous administration of GS1168 injection at dose level 2; 3. A single intravenous administration of GS1168 injection at dose level 3.
Sponsors
Gritgen Therapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse event (AE), including serious adverse event (SAE) and adverse event of special interest (AESI) | Week 52 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Phe levels | Week 52 | Change from baseline in plasma level of Phe following GS1168 injection administration |
| Total protein intake | Week 52 | Change from baseline in total protein intake following GS1168 injection administration |
| Phenylketonuria Quality of Life (PKU-QOL) scores | Week 52 | Change in Phenylketonuria Quality of Life Questionnaire (PKU-QOL, Score range: 0-100, higher scores indicate worse outcomes.) |
Countries
China
Contacts
CONTACTYuntao Gong, MD
CONTACTSihui Pan
Outcome results
None listed