A Multi-Center, Observational Study to Evaluate the Long-Term Safety of Subcutaneous Injections of Palynziq® (pegvaliase) in Subjects with Phenylketonuria (PALace)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  PALYNZIQ
• Study drug International non-proprietary name (INN) or common name:
  PEGVALIASE
• Anatomical Therapeutic Chemical (ATC) code:
  (A16AB19) pegvaliase

  pegvaliase
• Medical condition to be studied:
  Phenylketonuria

Population studied

• Age groups:
  • Paediatric Population (< 18 years)

    • Adolescents (12 to < 18 years)
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Hepatic impaired

  Renal impaired
• Estimated number of subjects:
  450

Study design details

• Main study objective:
  To further characterize the safety profile of pegvaliase, including hypersensitivity reactions, long-term safety and tolerability, and the effectiveness of the additional risk minimization measures (aRMM) (European Union EU only) in subjects receiving pegvaliase for the treatment of phenylketonuria (PKU) in a real-world setting.
• Outcomes:
  To quantify and characterize the risk of the protocol-defined safety events in incident users receiving pegvaliase for the treatment of PKU in a real-world setting ; • Acute systemic hypersensitivity reaction ; • Anaphylaxis ; • Angioedema ; • Serum sickness ; • Severe hypersensitivity reaction ; • Severe or Persistent (≥ 6 months) arthralgia ; • Severe injection site reaction ; • Hypophenylalaninemia, ; ; Quantify & characterize the risk of: ; • Complications of immune-complex formation or PEG accumulation resulting in end-organ damage, SAEs, Severe ADRs, ADRs leading to treatment interruption/discontinuation and/or study discontinuation. ; • Safety event in subject: receiving treatment with other PEG injectable with pre-existing hepatic and renal impairment with hypoPhe ≥ 65yr < 16yr (excl. Germany).
• Data analysis plan:
  The primary analysis is the incidence rate for each primary safety event will be calculated as the number of new events divided by the total exposure person-time at risk. The 95% confidence interval of the incidence rate will also be calculated. Additional analyses involving time to first event, incidence proportion, and event rate of each primary safety event will be explored using parametric and semi-parametric modeling. Analysis of the secondary endpoint will include the incidence rate of pre-specified safety events. In addition, incidence rates of each primary safety event and the safety events from the secondary endpoint will be provided within pre-specified subsets. Tertiary analysis will include the number and proportion of subjects in Europe who received aRRMs prior to the initiation of pegvaliase treatment. Tabulations of patient characteristics at enrolment and during the study will also be summarized.