A Clinical Study on the Safety and Tolerability of PL54 Injection in Adult Patients With Phenylketonuria (PKU)

Key Inclusion Criteria:

• Adult patients aged 18 to 55 years, inclusive, regardless of sex.

• Subjects with a prior diagnosis of phenylketonuria (PKU) meeting the following criteria:

  • Blood Phe concentration ≥600 µmol/L at screening;
  • Average blood Phe concentration ≥600 μmol/L within the 12 months prior to screening (with at least two test results available);
  • Genetic test report confirming the presence of phenylalanine hydroxylase (PAH) gene defects.
• Ability to maintain dietary stability from 3 days prior to screening through the end of the trial.
• Subjects (including partners) capable of practicing effective contraception during the trial period, with no plans for conception within 3 months after trial completion.
• Voluntarily sign the informed consent form and, in the investigator's judgment, able to comply with all study requirements.

Key Exclusion Criteria:

• Known hypersensitivity to PL54 injection or any of its excipients.
• Medical conditions or history assessed by the investigator that may increase the risk of severe allergic reactions (e.g., acute exacerbation of allergic asthma, atopic constitution, history of anaphylaxis, etc.).
• Use of any medication for PKU (including large neutral amino acids) within 14 days prior to study drug administration or within 5 half-lives of the drug (whichever is longer).
• Use or planned use of any injectable medication containing polyethylene glycol (PEG) (except the investigational drug) within 3 months prior to screening or during the study period, including medroxyprogesterone acetate injection.
• Prior use of Pegvaliase (PALYNZIQ®).
• History of any of the following manifestations associated with prior PEG-containing product use: systemic symptoms (e.g., respiratory or gastrointestinal symptoms, hypotension, angioedema, allergic reactions). The investigator will determine eligibility based on the severity of previous symptoms.
• Clinically significant abnormal vital signs, physical examination, laboratory tests, or other relevant findings at screening, deemed by the investigator to render the subject unsuitable for enrollment.
• Significant medical history of immunological, cardiovascular, respiratory, gastrointestinal, endocrine, renal, hematological, neurological, psychiatric, or malignant diseases (except basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been excised with no evidence of recurrence) assessed by the investigator prior to screening.
• Stable use of immunosuppressants (e.g., cyclosporine, azathioprine) within 4 weeks prior to screening, with inability to discontinue use during the study period.
• Vaccination within 4 weeks prior to screening or planned vaccination during the study period.
• Positive serology for Treponema pallidum-specific antibodies, human immunodeficiency virus (HIV) antibodies, hepatitis C virus (HCV) antibodies, or hepatitis B virus (HBV) surface antigen.
• Serum creatinine ratio > 1.5 × upper limit of normal (ULN).
• Alanine aminotransferase (ALT) > 2 × ULN.
• Pregnant or breastfeeding women.
• Participation in any investigational drug trial and receipt of an investigational product within 3 months prior to screening.
• Prior use of any gene therapy for phenylketonuria (including participation in clinical studies).
• Any other condition deemed by the investigator to preclude participation in the trial.