Immune Modulation During Palynziq® Treatment in Adults (IMPALA)

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