Dose-Finding Study to Evaluate the Safety, Efficacy, & Tolerability of Multiple Doses of rAvPAL-PEG in Subjects With PKU

Inclusion Criteria

• For subjects who did not participate in PAL-001, diagnosis of PKU with both of the following: Current blood Phe concentration of ≥ 600 mmol/L at Screening and average blood Phe concentration of ≥ 600 µmol/L over the past 3 years, using available data.
• For subjects who did not participate in PAL-001, evidence that the subject is a non-responder to Kuvan® treatment (ie, 4 weeks of treatment with 20 mg/kg/day of Kuvan®, insufficient response per investigator determination, and treatment end date ≥ 14 days prior to Day 1 [ie, first dose]). Subjects who have had a previous response to Kuvan® treatment but are not currently taking Kuvan® because of noncompliance and have been off treatment for ≥ 6 months prior to Screening are eligible for participation.
• Willing and able to provide written, signed informed consent, or, in the case of participants under the age of 18, provide written assent (if required) and written informed consent by a parent or legal guardian, after the nature of the study has been explained, and prior to any research-related procedures.
• Between the ages of 16 and 55 years, inclusive.
• Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy.
• Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
• Maintained a stable diet with no significant modifications during the 4 weeks preceding the administration of study drug.
• In generally good health as evidenced by physical examination, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and electrocardiogram (ECG) at Screening.
• Willing and able to comply with study procedures.

Exclusion Criteria

• Use of any investigational product (with the exception of rAvPAL-PEG) or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
• Use of any medication that is intended to treat PKU within 14 days prior to the administration of study drug.
• Use or planned use of any injectable drugs containing PEG (other than rAvPAL-PEG), including Depo-Provera, within 3 months prior to Screening and during study participation.
• A prior reaction that included systemic symptoms (eg, respiratory or gastrointestinal problems, hypotension, angioedema, anaphylaxis) to rAvPAL-PEG or a PEG containing product. Subjects with a prior systemic reaction of generalized rash may be eligible for participation per the discretion of the Principal Investigator in consultation with the Sponsor's Medical Officer.
• Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) or to breastfeed at any time during the study.
• Concurrent disease or condition that would interfere with study participation or safety (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease).
• Any condition that, in the view of the PI, places the subject at high risk of poor treatment compliance or of not completing the study.
• Alanine aminotransferase (ALT) concentration > 2 times the upper limit of normal.
• Creatinine > 1.5 times the upper limit of normal.