Safety, Tolerability, and Efficacy Study of rAvPAL-PEG Administered Daily in Subjects With Phenylketonuria (PKU)
Condition: Phenylketonuria
MeSH terms: Phenylketonurias
Intervention: rAvPAL-PEG
Intervention description: 0.06 mg/kg/day, 0.1 mg/kg/day, 0.2 mg/kg/day, 0.4 mg/kg/day, 0.6 mg/kg/day, 0.8 mg/kg/day
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 16 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: PEG PAL; PKU; injection;

Summary:

      The purpose of this study is to evaluate the effect of daily administration of rAvPAL-PEG on
      the reduction of blood Phe concentrations in subjects with PKU.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of PKU with both of the following: current blood Phe concentration of ≥ 600
             micromol/L at screening and average blood Phe concentration of ≥ 600 micromol/L over
             the past 3 years, using available data

          -  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 ≥ 4 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 legally authorized representative, after the nature of the study
             has been explained, and prior to any research-related procedures.

          -  Willing and able to comply with all study procedures.

          -  Between the ages of 16 and 70 years, inclusive.

          -  Negative pregnancy test at screening and willing to have additional pregnancy tests
             performed during the study for females of childbearing potential only. Females
             considered not of childbearing potential are those who have been in menopause for at
             least 2 years or have had a tubal ligation at least 1 year prior to screening, or who
             have had a total hysterectomy.

          -  Willing to use an acceptable method of contraception while participating in the study
             (sexually active subjects only).

          -  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 ECG at screening.

        Exclusion Criteria:

          -  Prior use of rAvPAL-PEG.

          -  Use of any investigational product 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.

          -  Known hypersensitivity to rAvPAL-PEG excipients.

          -  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 investigator, 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.