Immune Modulation During Palynziq® Treatment in Adults (IMPALA) for Phenylketonuria

This study, called IMPALA, is looking at how a medication called methotrexate (MTX) might help adults with Phenylketonuria (PKU) who are taking Palynziq®. PKU is a genetic condition where the body can't break down a substance called phenylalanine (Phe). Palynziq® helps lower Phe levels, but some people have immune reactions to it. This study wants to see if adding methotrexate can reduce these reactions and make Palynziq® work better. Researchers will measure your blood Phe levels and immune responses to Palynziq® at different times over 49 weeks. You can join if you are 18-65 years old with PKU and are either new to Palynziq® or have been taking it but still have high Phe levels. The study aims to enroll up to 12 participants, but its current status is unclear.

Study design: This is an open-label study, meaning you and your doctors will know which treatments you are receiving. It plans to enroll up to 12 participants across two groups.
What's involved: You will receive Palynziq® by injection and take oral methotrexate once weekly. Your blood will be tested at various points over 49 weeks to measure Phe levels and immune responses.
Compensation: Not stated in the trial record.
Follow-up: Your blood Phe levels and immune responses will be monitored up to Week 49 of the study.

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Immune Modulation During Palynziq® Treatment in Adults (IMPALA)

Recruiting

PHASE4Ages 18–65InterventionalTreatment

BioMarin Pharmaceutical

~12 participants

Updated 2026-06-17 on ClinicalTrials.gov

What's tested:PegvaliaseMethotrexate

At a glance

Recruiting sites

1 of 12 listed sites are recruiting right now

RecruitingSuspended, closed, or not yet open

What they're measuring

Change in blood Phe levels from baseline to Week 25 and Week 49

Measured over Baseline to Week 25 and Baseline to Week 49

+1 more outcome measured

Conditions

Phenylketonuria

Where it's being run

12 sites across 12 states

California1

Colorado1

Florida1

Illinois1

Indiana1

Minnesota1

New York1

Oregon1

Study leadership

Medical Director, MD · STUDY_DIRECTOR · BioMarin Pharmaceutical

Who to contact

Trial Specialist

[email protected]

1-800-983-4587

Email the study team

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

Adults between 18 and 65 years old

Have a confirmed diagnosis of phenylketonuria (PKU)

Are in generally good health based on medical evaluation

Are willing and medically eligible to receive Palynziq and methotrexate (MTX) Cohort A: Have never taken Palynziq before and are willing to start it during the study Cohort B: Have blood \> 600 μmol/L after taking Palynziq for at least 24 weeks, are on a daily dose of at least 20mg and unable to increase the dose further

Agree to use required contraception if they or their partner could become pregnant

Are willing to carry two epinephrine devices at all times during Palynziq treatment

Exclusion

Pregnant, breastfeeding, planning to become pregnant, planning to father a child, or not using effective birth control if applicable

Have a known severe allergy or hypersensitivity reaction to methotrexate (MTX), Palynziq, or other PEG-containing medications

Have a serious active infection or a history of severe or recurrent infections

Have significant medical conditions that may affect safety or participation (such as serious heart, lung, liver, kidney, immune, neurological, psychiatric, or cancer-related conditions)

Have a history of substance or alcohol abuse within the past 12 months

Have had an organ transplant or are taking chronic immunosuppressive medications

Are currently taking medications that are not allowed in the study, including other PKU treatments besides Palynziq

Are using, or plan to use, injectable PEG-containing medications other than Palynziq during the study

Have major surgery planned during the study participation period

Are currently participating in another clinical study involving Palynziq

In the opinion of the study doctor, are not a suitable candidate for the study or may have difficulty complying with study requirements

What this trial measures

Change in blood Phe levels from baseline to Week 25 and Week 49Baseline to Week 25 and Baseline to Week 49
To evaluate blood Phe response in adults with PKU co-administered Palynziq with MTX for 6 months
Anti-PEG IgG, IgM, anti-PAL IgG, IgM levels at Weeks 5, 9, 25, and 49Baseline to Week 5, Week 9, Week 25, and Week 49
To evaluate the ability of MTX to modulate the immune response to Palynziq in adults with PKU

Trialytics