Rapid Drug Desensitization Study in Adults Experiencing Hypersensitivity Reactions to Palynziq (PALLADIUM)

A Phase 4 Study to Evaluate the Impact of a Rapid Drug Desensitization (RDD) Protocol for Adults With Phenylketonuria and Experiencing Hypersensitivity Reactions to Palynziq

The purpose of this study is to determine if rapid drug desensitization (RDD) to Palynziq will improve drug tolerability and treatment persistence in adult patients on commercial Palynziq experiencing hypersensitivity reactions (HSRs) leading to treatment interruption or reduction of dose or dosing frequency. See Section 10.8 for full list of HSR preferred terms. Study details include:

• Study duration: Up to 30 weeks (up to 6 weeks for Screening, then RDD, and 24 weeks of follow-up)
• RDD duration: 1 day
• Palynziq dosing/follow-up duration: 24 weeks
• Palynziq dosing frequency: Individualized

Study Overview

• Status: Active, not recruiting
• Conditions: Phenylketonuria; PKU
• Intervention / Treatment: Drug: RDD to Palynziq

Detailed Description

This is a Phase 4 study to evaluate the impact of RDD on adult (≥18 years old) participants with PKU who have experienced HSRs leading to treatment interruption or reduction of dose or dosing frequency while receiving commercial Palynziq. This is not a blinded study. All participants will undergo the same assessments: Screening, the RDD in clinic on Day 1, in clinic dosing on Day 2, followed by remote visits in weeks 2-24 post-RDD to monitor for HSRs and changes in Palynziq dosing. Remote visits will occur every other week from Week 2 through Week 12, then monthly until Week 24.

The total duration of participation in the trial will be approximately 30 weeks: up to 6 weeks for screening, followed by RDD and 24 weeks of post-RDD follow-up.

No Data Monitoring Committee (DMC) will be used for this trial.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • Uncommon Cures

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age:

  1.Participants must be 18 years of age or older inclusive, at the time of signing the informed consent.

• Type of Participant and Disease Characteristics 2. Participants must have phenylketonuria and must have been receiving commercial Palynziq and enrolled in the REMS.

  3. Participants must have developed HSRs leading to treatment interruption or reduction of dose or dosing frequency (Graade 2 or above) while on Palynziq, and must be able to undergo RDD within 6weeks from the reactive HSR and last Palynziq dose.

• Sex and Contraceptive/Barrier Requirement 4. Males and females are eligible to participate in this clinical study. Contraceptive use is not required during the study. Please refer to the Pregnancy section of USPI for further information.
• Informed Consent 5. Participants must be capable of giving written informed consent as described in Section 10.1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

• Medical Conditions:

  1. Participant may not have any kind of disorders that, in the opinion of the investigator, may compromise the ability of the participant to give written informed consent and/or comply with any aspect of the study, and/or where any aspect of participation would be medically inadvisable for the underlying disorder.
  2. Participant must not be pregnant on the day of the RDD.
  3. Participants with uncontrolled asthma, active upper respiratory infection or other active infections, or cardiovascular disease. Asthma control will be assessed using the Asthma Control Test at screening.

• Prior/Concomitant Therapies:

  4. Participants were not using antihistamine premedication(s) at the time of reactive HSRs.

  5. Participants are willing and able to resume and tolerate Palynziq at the reactive dose prior to the RDD.

  6. Participant must not be receiving concurrent injectables containing PEG with the exception of PEG-containing vaccines, such as COVID-19 vaccinations (see Section 6.7).

  7.Participants receiving beta blockers.

• Prior/Concurrent Clinical Study Experience 8. Participants may not be currently participating in an interventional study of any investigational product, device, or procedure, or any other BioMarin clinical trial or post-marketing study.

Other Exclusions 9. Participants must not be experiencing reactions that are not appropriate for RDD, including severe cutaneous adverse reactions (SCAR) as defined by the American Academy for Allergy, Asthma, and Immunology.

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: RDD; Participants undergoing RDD to Palynziq	Drug: RDD to Palynziq; Delivery of gradually increasing doses of Palynziq at fixed time intervals over the course of several hours to a cumulative dose equal to the reactive dose. Reactive dose is defined as the dose at which the reactive HSR occurred which led to treatment interruption or reduction of dose or dose frequency.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine if RDD to Palynziq improves drug tolerability and treatment persistence in adults with PKU experiencing HSRs leading to treatment interruption or reduction of dose or dosing frequency (reactive HSR).	Tolerance, defined as the ability to restart Palynziq at the dose at which the reactive HSR occurred (reactive dose) and escalate as appropriate within 24 weeks following the RDD, without requiring treatment interruption or reduction of dose or dosing frequency due to HSRs and reduction in occurrence of HSRs Grade 2 or above within 24 weeks following RDD	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize the immune response to Palynziq following RDD	Change in PEG IgG and IgM, PAL IgG and PAL IgM, and C3/C4 from Baseline to after RDD and at Week 24	24 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: January 13, 2025
• First Submitted That Met QC Criteria: January 13, 2025
• First Posted (Actual): January 17, 2025

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Phenylketonuria; PKU; Palynziq; pegvaliase
• 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: 165-402

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No