Pegvaliase

(165-306 [PEGASUS])

Trial Status Active, Not Recruiting

Condition

Phenylketonuria

Technology

• Enzyme

Title

Study to Evaluate the Safety and Efficacy of Pegvaliase in Adolescents (Ages 12-17) With Phenylketonuria (PEGASUS)

Study Description

This is a Phase 3, open-label, randomized, controlled study enrolling approximately 54 adolescents with PKU. The study is designed to assess the safety and efficacy of pegvaliase injections.

Primary Outcome Measures*

• Change in blood Phe concentration
• Incidence of treatment-emergent adverse events as assessed by CTCAE v5.0

Select Inclusion Criteria*

• Must be 12 to 17 years old
• Signed informed consent

Secondary Outcome Measures*

• Change in total dietary protein intake

Select Exclusion Criteria*

• Previous treatment with pegvaliase
• Use of any medication that is intended to treat PKU within 14 days prior to administration

* Additional measures/criteria may apply.
CTCAE v5.0, Common Terminology Criteria for Adverse Events version 5.0; Phe, phenylalanine; PKU, phenylketonuria.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT05270837

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Pegvaliase

(165-402 [PALLADIUM])

Trial Status Recruiting

Condition

Phenylketonuria

Technology

• Enzyme

Title

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

Study Description

This is a Phase 4 study to evaluate the impact of rapid drug desensitization (RDD) on adult (≥18 years old) participants with PKU who have experienced hypersensitivity reactions (HSRs) leading to treatment interruption or reduction of dose or dosing frequency while receiving commercial Palynziq.

Primary Outcome Measures*

• 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 2. Reduction in occurrence of HSRs Grade 2 or above within 24 weeks following RDD

Select Inclusion Criteria*

• 18 years of age or older
• Have phenylketonuria and been receiving commercial Palynziq and enrolled in the REMS
• Have developed HSRs leading to treatment interruption or reduction of dose or dosing frequency (Grade 2 or above) while on Palynziq, and be able to undergo RDD within 6 weeks from the reactive HSR and last Palynziq dose

Secondary Outcome Measures*

• Change in PEG IgG and IgM, PAL IgG and PAL IgM, and C3/C4 from Baseline to after RDD and at Week 24

Select Exclusion Criteria*

• Medical Conditions:
  Pregnant on the day of the RDD
  Uncontrolled asthma, active upper respiratory infection or other active infections, or cardiovascular disease
• Prior/Concomitant Therapies:
  Not using antihistamine premedication(s) at the time of reactive HSRs
  Willing and able to resume and tolerate Palynziq at the reactive dose prior to the RDD
  Receiving concurrent injectables containing PEG with the exception of PEG-containing vaccines, such as COVID-19 vaccinations
  Receiving beta blockers

* Additional measures/criteria may apply.

REMS, Risk Evaluation & Mitigation Strategy; HSR, Hypersensitivity Reactions; PEG, Polyethylene glycol; PAL, Phenylalanine ammonia lyase; IgG, Immunoglobulin G; IgM, Immunoglobulin M;

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT06780332

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Pegvaliase

(165-501[PALace])

Trial Status Recruiting

Condition

Phenylketonuria

Technology

• Enzyme

Title

A Long-term, Post-marketing Safety Study of Palynziq in Patients With PKU (PALace)

Study Description

This is a 10-year multicenter, global, observational study 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 (aRMMs) (European Union [EU] only) in subjects receiving pegvaliase for the treatment of PKU.

Primary Outcome Measures*

• To quantify and characterize the risk of protocol-defined safety events in incident-users receiving pegvaliase for the treatment of PKU in a real-world setting

Select Inclusion Criteria*

• Documented diagnosis of PKU per local standard of care
• Receiving or plan to receive pegvaliase treatment within 30 days of enrollment

Secondary Outcome Measures*

• To quantify and characterize the risk of protocol-defined safety events in subjects receiving pegvaliase for the treatment of PKU in a real-world setting

Select Exclusion Criteria*

• Subject has any kind of disorder that may compromise the ability of the subject to give written informed consent
• Currently participating in an interventional study of any investigational product, device, or procedure

* Additional measures/criteria may apply.
PKU, phenylketonuria.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT05813678

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Pegvaliase

(165-503 [PALisade])

Trial Status Recruiting

Condition

Phenylketonuria

Technology

• Enzyme

Title

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

Study 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).

Primary Outcome Measures*

• 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

Select Inclusion Criteria*

• Enrolled at US sites participating in the 165-501 (PALace) study.

Secondary Outcome Measures*

• Immunologic and inflammatory responses (immunologic testing, inflammatory markers) associated with occurrences of end-organ function (e.g., kidney, liver) related, immune-mediated adverse drug reactions
• The potential association between immunologic responses and blood Phe levels

Select 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)

* Additional measures/criteria may apply.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT06305234

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4

Pegvaliase

(165-504 [PALomino])

Trial Status Recruiting

Condition

Phenylketonuria

Technology

• Enzyme

Title

A Global, Multicenter Study to Assess Maternal, Fetal and Infant Outcomes of Exposure to Palynziq® (Pegvaliase) During Pregnancy and Breastfeeding (PALomino)

Study Description

This is a Phase 4 observational study designed to assess the impact of Palynziq® (pegvaliase) treatment in pregnant women with PKU and on their offspring who were exposed to pegvaliase at any time during pregnancy and breastfeeding.

Primary Outcome Measures*

• Pregnancy outcome and infant development for women who have been treated with Palynziq (pegvaliase) within 2 weeks of their last menstrual period

Select Inclusion Criteria*

• Subject or legal guardian consent
• Confirmation of ongoing pregnancy
• Diagnosed with PKU

Secondary Outcome Measures*

• Pregnancy outcomes
• Serious adverse events
• Maternal pegvaliase use during breastfeeding

Select Exclusion Criteria*

• Currently participating in a BioMarin-sponsored interventional study

* Additional measures/criteria may apply.
PKU, phenylketonuria.

For reference and comprehensive trial information, visit ClinicalTrials.gov NCT05579548

Pre-IND

Phase 1

Phase 2

Phase 3

Phase 4