Recruiting

Palynziq with MTX

Sponsor:

BioMarin Pharmaceutical

Code:

NCT07477691

Conditions

Phenylketonuria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Pegvaliase

Methotrexate

Study Details

Brief summary:

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.

Conditions

Phenylketonuria

Study ID

NCT07477691

Start date

May 29, 2026

Status verified date

Jun, 2026

Completion date

Sep 30, 2027

Anticipated

Primary completion date

Sep 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

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 Design

Enrollment

12 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Palynziq naïve

Individuals with uncontrolled blood phenylalanine (Phe) > 600 μmol/L on existing management who have never been treated with Palynziq. 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. 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).

experimental: Palynziq experienced

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). 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).

Interventions

Pegvaliase

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

Methotrexate

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

Primary outcome measure

  • Change in blood Phe levels from baseline to Week 25 and Week 49 [ Time Frame: Baseline to Week 25 and Baseline to Week 49 ]
  • Anti-PEG IgG, IgM, anti-PAL IgG, IgM levels at Weeks 5, 9, 25, and 49 [ Time Frame: Baseline to Week 5, Week 9, Week 25, and Week 49 ]

Central Contacts and Locations

Central contacts

Trial Specialist

1-800-983-4587medinfo@bmrn.com

Locations

UT Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

More Information

Sponsor

BioMarin Pharmaceutical

Last update posted

Jun 17, 2026

Last verified

Jun, 2026

Keywords

  • PKU
  • Phenylketonuria
  • Pegvaliase
  • Palynziq
  • Methotrexate
  • Immune Response
  • Safety
  • Immune Modulation
  • BMN 165-401
  • Hyperphenylalaninemia
  • Enzyme Substitution Therapy
  • Pharmacologic Immunosuppression

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by BioMarin Pharmaceutical on 2026-06-17.