ClinicalTrials.gov record NCT07477691

Immune Modulation During Palynziq® Treatment in Adults (IMPALA)

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 6, 2026

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

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 4A study of a treatment that is already approved, to learn more about its long-term effects, safety or use in everyday practice.
Age18 years old to 65 years old
SexAll
LocationUnited States
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This Phase 4, open-label study evaluates methotrexate given together with Palynziq in adults with PKU and uncontrolled blood phenylalanine. Up to 12 adults are planned in two parallel cohorts: people who are Palynziq‑naïve and people already treated with Palynziq. Participants receive weekly oral methotrexate plus Palynziq injections per usual prescribing guidance, with a 24‑week combination period and a further 24‑week follow-up on Palynziq alone.

What it is studying. The study tests whether giving oral methotrexate together with Palynziq changes the immune response against Palynziq (measured by anti-PEG and anti-PAL antibodies) and how that relates to blood phenylalanine levels, safety events, and Palynziq blood levels.

What the researchers hope to learn. To evaluate whether methotrexate modulates the immune response to Palynziq, to measure changes in blood phenylalanine, to assess safety (treatment‑emergent adverse events), and to characterize Palynziq pharmacokinetics when given with methotrexate.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Methotrexate
Biological
  • Pegvaliase

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

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

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

The overall objective of the study is to evaluate the ability of MTX, when co-administered with Palynziq, to suppress immune responses to Palynziq and thus improve the tolerability and efficacy of Palynziq in adults with phenylketonuria (PKU). Up to 12 participants will be enrolled into the study across 2 cohorts, with a target enrollment of 6 participants into each cohort:

  • Cohort A: Individuals with uncontrolled blood phenylalanine (Phe) > 600 μmol/L on existing management who have never been treated with Palynziq (Palynziq naïve)
  • Cohort B: Individuals who have uncontrolled blood Phe > 600 μmol/L after ≥ 24 consecutive weeks of treatment with Palynziq, are on a current dose of≥ 20mg/day, and are unable to further dose escalate (Palynziq experienced)

Palynziq will be initiated (Cohort A) or will continue (Cohort B) as indicated in the Palynziq United States Prescribing Information (USPI) and as prescribed by the participant's treating physician. The decision to initiate or continue Palynziq must be made independently of participation in this study. Palynziq and MTX will not be supplied by BioMarin as part of participation in this study. All participants will be administered MTX at an oral dose of 15 mg/week concurrent with Palynziq:

  • Cohort A participants will have a 4-week Screening Period, followed by a 4-week MTX Tolerability Period during which only MTX will be administered. If MTX is tolerated during the MTX Tolerability Period, the participant will then enter the 24-week Combination Treatment Period during which MTX + Palynziq will be administered concurrently.
  • Cohort B participants will have a 4-week Screening Period. Participants will then have 24 weeks of concurrent MTX + Palynziq treatment (Combination Treatment Period): participants will be assessed for MTX tolerability during the first 4 weeks of MTX + Palynziq (MTX Tolerability Period) and then receive another 20 weeks of MTX + Palynziq.

After completion of Week 24 (Combination Treatment Period), MTX will be discontinued for both cohorts and Palynziq only will continue for another 24 weeks (to Week 49; Follow-up Period). Participants will be assessed for safety and MTX tolerability. If a participant in either Cohort A or B is unable to tolerate MTX, the participant will be discontinued from MTX treatment. Participants who discontinue from MTX early should continue to complete the remaining study assessments until as long as such continued participation will not detrimentally affect the health, safety, and welfare of the participant per investigator determination

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

After a 4-week screening, Cohort A will have a 4-week oral MTX (15 mg/week) tolerability period before starting Palynziq; Cohort B will enter 24 weeks of concurrent MTX (15 mg/week) plus Palynziq. Both cohorts receive 24 weeks of combined treatment, then MTX is stopped and Palynziq-only follow-up continues to Week 49. Study visits include safety checks and regular blood tests to measure phenylalanine and antibody levels and monitoring of MTX tolerability; MTX will be discontinued if not tolerated. Participants must follow contraception requirements and carry two epinephrine devices while on Palynziq. The registry says BioMarin will not supply Palynziq or methotrexate as part of the study. Palynziq is prescribed by the participant’s own treating physician, following its US prescribing information, and the registry says the decision to start or continue it must be made independently of taking part in this study.

How the study is structured. Interventional, non-randomized, open-label, parallel groups. Participants begin with a screening period; methotrexate 15 mg taken once weekly is given during a short tolerability period and then together with Palynziq for 24 weeks. After Week 24 methotrexate is stopped and Palynziq continues for another 24 weeks. The study plans up to 12 participants across two cohorts (Palynziq‑naïve and Palynziq‑experienced).

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on phenylketonuria

Clinical trials38 trials listed for phenylketonuriaEvery trial the registry lists for phenylketonuria, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in phenylketonuria researchLatest monthly update: September 2026. Includes: Diet supply gaps. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
May 29, 2026
Primary completion
Sep 30, 2027 (estimated)
Study completion
Sep 30, 2027 (estimated)
Target enrollment
12 participants (estimated)
Last updated on registry
Jun 17, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
BioMarin Pharmaceutical

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (12)

  • UCLA Dept. of Human GeneticsNot Yet Recruiting

    Los Angeles, California, 90095 · United States

  • Children's Hospital ColoradoNot Yet Recruiting

    Aurora, Colorado, 80045 · United States

  • University Of South Florida Medical CenterNot Yet Recruiting

    Tampa, Florida, 33613 · United States

  • Ann & Robert H. Lurie Children's Hospital of ChicagoNot Yet Recruiting

    Chicago, Illinois, 60611 · United States

  • Indiana University School of MedicineNot Yet Recruiting

    Indianapolis, Indiana, 46202 · United States

  • University of Minnesota Medical SchoolNot Yet Recruiting

    Minneapolis, Minnesota, 55455 · United States

  • University of Rochester Medical Center (URMC)Not Yet Recruiting

    Rochester, New York, 14642 · United States

  • Oregon Health & Science University (OHSU) - PARENTNot Yet Recruiting

    Portland, Oregon, 97239 · United States

  • University of Pittsburgh Medical Center (UPMC) - Children's Hospital of PittsburghNot Yet Recruiting

    Philadelphia, Pennsylvania, 19104 · United States

  • UT Southwestern Medical CenterRecruiting

    Dallas, Texas, 75390 · United States

    • Markey McNutt

Terms used on this page · explanations by MedicalUpdates.ai

open-label
No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
Cohort
A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
immunosuppressive
A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
target enrollment
The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
Screening Period
The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
Follow-up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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