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.
Adult patients aged 18 to 55 years, inclusive, regardless of sex.
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.
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.
Single group
PL54
Biological/VaccinePhase 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.
Adverse Events (AEs)
including the incidence of overall and categorized AEs
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.
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.
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.
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).
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