Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 4INTERVENTIONAL

Immune Modulation During Palynziq® Treatment in Adults (IMPALA)

A Phase 4 Study of Immune Modulation During Palynziq® Treatment in Adults With Phenylketonuria (PKU)

Immune Modulation During Palynziq® Treatment in Adults (IMPALA) (NCT07477691) is a Phase 4 interventional studying Phenylketonuria, sponsored by BioMarin Pharmaceutical. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

What Stage of Research Is This?

Phase 4 studies happen after a treatment has been approved by the FDA. They monitor long-term safety, real-world effectiveness, and any rare side effects that only emerge in larger populations over longer periods. Phase 4 results sometimes lead to label changes, additional warnings, or — rarely — withdrawal of approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 12 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 Who Should NOT Join This Trial: - 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 Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * 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 Criteria: * 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

Treatments Being Tested

BIOLOGICAL

Pegvaliase

Pegvaliase (Palynziq) administered by subcutaneous injection. Dosing follows U.S. Prescribing Information and investigator judgement.

DRUG

Methotrexate

Oral methotrexate 15 mg administered once weekly during the Tolerability Period and the Combination Treatment Period.

Locations (12)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

UCLA Dept. of Human Genetics

Los Angeles, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

University Of South Florida Medical Center

Tampa, Florida, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Indiana University School of Medicine

Indianapolis, Indiana, United States

University of Minnesota Medical School

Minneapolis, Minnesota, United States

University of Rochester Medical Center (URMC)

Rochester, New York, United States

Oregon Health & Science University (OHSU) - PARENT

Portland, Oregon, United States

University of Pittsburgh Medical Center (UPMC) - Children's Hospital of Pittsburgh

Philadelphia, Pennsylvania, United States

UT Southwestern Medical Center

Dallas, Texas, United States

University of Utah Hospital

Salt Lake City, Utah, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT07477691), the sponsor (BioMarin Pharmaceutical), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT07477691 clinical trial studying?

Study 165-401 is a Phase 4, open-label study designed to examine the concomitant use of methotrexate (MTX) to suppress immune responses to Palynziq and improve tolerability and efficacy in adults with PKU. The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT07477691?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT07477691?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

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Source: ClinicalTrials.gov API v2 record for NCT07477691. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT07477691. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-26 · Data from ClinicalTrials.gov.