A Long Term, Post-marketing Study of Immune Response in Patients Receiving Palynziq Treatment for PKU (PALisade)

A Multi-Center, Prospective, Longitudinal, Study Evaluating Immunologic, Inflammatory, and Laboratory Parameters Associated With Long-Term Palynziq® (Pegvaliase) Treatment in Subjects With Phenylketonuria (PKU) in the United States

This is a 10-year multi-center, prospective, longitudinal, single arm study evaluating immunologic, inflammatory and laboratory parameters associated with long-term Palynziq treatment in subjects with phenylketonuria (PKU) in the United States (US). Subjects in the US for whom a clinical decision has been made that they will receive pegvaliase to treat their PKU within 30 days following the date of enrollment in Study 165-501 (incident-users) or who have previously started treatment with pegvaliase at the date of enrollment in Study 165-501 (prevalent-users) are eligible for participation in Study 165-503.

Study Overview

• Status: Recruiting
• Conditions: Phenylketonuria (PKU)
• Intervention / Treatment: Drug: Pegvaliase

Detailed Description

This is a 10-year multi-center, prospective, longitudinal, single arm study evaluating immunologic, inflammatory and laboratory parameters associated with long-term Palynziq treatment in subjects with phenylketonuria (PKU) in the United States (US). Subjects in the US for whom a clinical decision has been made that they will receive pegvaliase to treat their PKU within 30 days following the date of enrollment in Study 165-501 (incident-users) or who have previously started treatment with pegvaliase at the date of enrollment in Study 165-501 (prevalent-users) are eligible for participation in Study 165-503. Subjects participating in the 165-501 study who consent to participate in this study (165-503) will be requested to provide pre-dose blood samples for Phe, immunologic and inflammatory marker testing approximately every 3 months for the first 3 years of participation, then every 6 months for the remainder of the study. Subjects will be requested to provide additional pre-dose blood samples at the time of Study 165-501 -protocol defined safety events. Additional pre-dose samples will be drawn as per standard of care as detailed in protocol 165-501. The blood Phe, immunologic (PAL IgG, PEG IgG, PEG IgM, anti-pegvaliase IgE), and inflammatory (C3/C4, hsCRP) markers, will be sent to a central laboratory for processing. Data collected in the 165-501 study will be combined with the data collected in this study to decrease burden on sites for data entry and to avoid duplication of ADR reporting (see Criteria for Evaluation). The combined data will be reported in the Clinical Study Report for this study. Subjects can withdraw from Study 165-503 and remain on Study 165-501, but they cannot withdraw from Study 165-501 and remain on Study 165-503 as safety events and other data-points are collected in Study 165-501.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Medical Director, MD; Phone Number: 1-800-983-4587; Email: medinfo@bmrn.com
• Study Contact Backup: Name: 165-503 Program Director; Phone Number: 1-800-983-4587; Email: medinfo@bmrn.com

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Recruiting
      • Tulane University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Subjects enrolled at US sites participating in the 165-501 study.

Description

Inclusion Criteria:

• Subjects enrolled at US sites participating in the 165-501 study.

Exclusion Criteria:

• Legal incapacity or limited legal capacity without legal guardian representation.
• Subject is unable or unwilling to provide informed consent for the additional interventional burden of the study (blood sampling).

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate immunologic and inflammatory responses associated with occurrences of	Acute systemic hypersensitivity reaction; Anaphylaxis; Angioedema; Serum sickness; Severe hypersensitivity reaction; Severe or Persistent arthralgia; Severe injection site reaction	A maximum of 10 years treatment duration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of immunologic and/or inflammatory responses over time	To evaluate immunologic and inflammatory responses (immunologic testing, inflammatory markers) associated with occurrences of end-organ function (eg, kidney, liver) related, immune-mediated adverse drug reactions (ADRs)*	A maximum of 10 years treatment duration.
Evaluation of immunologic responses over time	To evaluate the potential association between immunologic responses and blood Phe levels * A list of end-organ function related, immune-mediated ADRs is included as an appendix to the statistical analysis plan (SAP).	A maximum of 10 years treatment duration.

Collaborators and Investigators

• Sponsor: BioMarin Pharmaceutical
• Investigators: Study Director: Medical Director, MD, BioMarin Pharmaceutical

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2024
• Primary Completion (Estimated): November 18, 2033
• Study Completion (Estimated): November 18, 2033

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: March 8, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: observational; Phenylketonuria; PKU; safety study; Palynziq; pegvaliase; immunogenicity assessment; inflammatory assessment
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Phenylketonurias
• Other Study ID Numbers: 165-503

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No