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

A Phase I Multicenter Open-label Dose-escalation Study of Safety, Tolerability, PK/PD and Immunogenicity of Single/Multiple Subcutaneous PL54 Injection in Adult PKU Patients

The primary objective of this clinical trial is to evaluate the safety and tolerability of single and multiple administrations of PL54 in patients aged 18-55 years. The key questions it aims to answer include:

How safe and tolerable is PL54 in PKU patients following single and multiple administrations?

Researchers will compare the safety and tolerability profiles between single and multiple dosing regimens to assess PL54.

Participants will be required to:

Phase Ia (Single Administration):

Receive a single subcutaneous injection of PL54 based on body weight. Undergo a 28-day observation period post-injection. Visit the clinic for assessments on: D1 (administration day), D2, D7, D8, D10, D15, D22, and D29.

Phase Ib (Multiple Administrations):

Receive subcutaneous injections of PL54 every 7 days (4 doses total) based on body weight. Undergo a 35-day observation period after the last injection. Visit the clinic for assessments on: D1 (first administration), D3, D8, D15, D21, D22, D29, D36, D43, and D57

Data to be recorded include:

Incidence, severity, seriousness, relationship to PL54 treatment, duration, and outcome of adverse events (AEs).

Change from baseline in blood phenylalanine (Phe) concentration.

Study Overview

• Status: Recruiting
• Conditions: Phenylketonuria (PKU)
• Intervention / Treatment: Biological: PL54

Detailed Description

This is a multicenter, open-label, dose-escalation Phase I clinical study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of single or multiple subcutaneous injections of PL54 injection in adult patients with phenylketonuria (PKU). The trial is divided into Phase Ia and Phase Ib.

Phase Ia:

A single subcutaneous injection will be administered. The phase includes a 2-week screening period, a single administration on Day 1 (D1), and a 4-week follow-up period, totaling approximately 6 weeks. Approximately 30 subjects will be enrolled across five dose groups: 0.01 mg/kg, 0.04 mg/kg, 0.1 mg/kg, 0.25 mg/kg, and 0.5 mg/kg, with 6 subjects per group (including 1 sentinel). The first subject in each dose group will receive a single subcutaneous injection of PL54, and the remaining subjects in the same dose group will be enrolled only after the first subject has completed at least 14 days of safety assessment. Dose escalation to the next group will proceed only after all subjects in the previous dose group have completed at least 14 days of visit assessments and the Safety Monitoring Committee (SMC) determines that the dose escalation termination criteria have not been met.

Phase Ib:

Approximately 18 subjects will be enrolled. Subcutaneous injections will be administered once weekly for 4 consecutive weeks (the dosing period for subsequent dose groups may be adjusted based on observed anti-drug antibody [ADA], pharmacokinetic [PK], and pharmacodynamic [PD] results from previous dose groups). Three dose groups are planned: 0.04 mg/kg, 0.1 mg/kg, and 0.25 mg/kg, with 6 subjects per group (the actual dose groups and dosing regimen will be adjusted based on Phase Ia results). Dose escalation to the next group will proceed only after all subjects in the previous dose group have completed at least 28 days of visit assessments and the SMC determines that the dose escalation termination criteria have not been met.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jing Sun; Phone Number: 86-13983367811; Email: sunj@pegbiocq.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • Recruiting
      • The First Affiliated Hospital of Anhui Medical University
      • Principal Investigator: Huan Zhou
      • Contact: Huan Zhou; Phone Number: 86-13983367811; Email: sunj@pegbiocq.com
      • Principal Investigator: Jianping Weng

Participation Criteria

Eligibility Criteria

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

Description

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.

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: PL54; subcutaneous injection administration. Single -dose escalation will start from the initial dose of 0.01 mg/kg and proceed sequentially to higher doses.

Biological: PL54; Phase Ia: Single, subcutaneous injection administration. Dose escalation will start from the initial dose of 0.01 mg/kg and proceed sequentially to higher doses. Phase Ib: Administration via subcutaneous injection. Dosing frequency: once weekly. Dose escalation will start from the initial dose of 0.04 mg/kg and proceed sequentially to higher doses.; Other Names: PEGylated Recombinant Phenylalanine Ammonia-Lyase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	including the incidence of overall and categorized AEs	Day 1-29 of Phase Ia; Day 1-57 of Phase Ib

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in blood phenylalanine concentration from baseline	Comparing the average phenylalanine concentrations at different timepoints and different doses with the concentration at baseline in Phase Ia and Phase Ib studies.	Day 1-29 of Phase Ia; Day 1-57 of Phase Ib
The proportion of subjects whose blood phenylalanine concentration decreased to the target range (60-600 μmol/L)	Monitor the blood phenylalanine concentration at each visit and calculate the proportion of subjects whose phenylalanine concentration drops to the target range (60-600 μ mol/L) for each dose group in Phase Ia and Phase Ib studies.	Day 1-29 of Phase Ia; Day 1-57 of Phase Ib
PK parameters of PL54 after single dose and multiple doses	Calculate the following PK parameters, including but not limited to Cmax, Tmax, AUC0-t, AUC0-∞, T1/2, λz, CL/F, Vz/F for Phase Ia, and AUC0-τ, Cmin,ss, Cmax,ss, Tmax,ss, T1/2 for Phase Ib.	Day 1-29 of Phase Ia; Day 1-57 of Phase Ib
Immunogenicity of PL54	Total anti-drug antibodies (if applicable), anti-PAL4 antibodies, anti-PEG IgG/IgM, neutralizing antibodies that inhibit PL54 activity (NAbs), and detection of anti-PL54 IgE antibodies in subjects experiencing severe allergic reactions (WAO criteria).	Day 1-29 of Phase Ia; Day 1-57 of Phase Ib

Collaborators and Investigators

• Sponsor: Chongqing Peg-Bio Biopharm Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: June 17, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 29, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 28, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Phenylketonuria; PKU
• 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: PL54-A101

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