A Study to Evaluate Subcutaneously Administered rAvPAL-PEG in Patients With Phenylketonuria for 24 Weeks
Condition: Phenylketonuria
MeSH terms: Phenylketonurias
Intervention: BMN 165 (rAvPAL-PEG)
Intervention description: Subcutaneous injection of rAvPAL-PEG administered from 1 time up to 5 times per week between 2.5mg up to a maximum of 375mg for 24 weeks.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 16 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: PKU; Injections; PEG-PAL; PAL

Summary:

      The primary objective of the study is to evaluate the effect of dosing regimens of multiple
      subcutaneous (SC) doses of rAvPAL-PEG to induce an early and sustained Phe reduction while
      decreasing the frequency and severity of hypersensitivity reactions in patients with PKU.
    

Eligibility criteria:

        Inclusion Criteria:

          1. A diagnosis of PKU, with the following:

               -  Current blood Phe concentration of ≥ 600 µmol/L at Screening.

               -  Average blood Phe concentration of ≥ 600 µmol/L over the past 6 months, using
                  available data.

               -  Naïve to prior treatment with rAvPAL-PEG.

          2. Evidence that the patient is a non responder to Kuvan® treatment (ie, 4 weeks of
             treatment with 20 mg/kg/day of Kuvan, insufficient response per investigator
             determination, unsuitable for Kuvan® per Investigator determination, and treatment end
             date ≥ 2 days prior to Day 1 [ie, first dose]). Patients 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.

          3. Willing and able to provide written, signed informed consent after the nature of the
             study has been explained and prior to any research-related procedures. In the case of
             participants under the age of 18 or participants who have been deemed mentally unable
             to provide informed consent, a parent or legal guardian may provide written informed
             consent (and, if required, the patient will provide written assent).

          4. Willing and able to comply with all study procedures.

          5. Between the ages of 16 and 70 years, inclusive.

          6. 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.

          7. Sexually active patients must be willing to use an acceptable method of contraception
             while participating in the study.

          8. Maintained a stable diet with no significant modifications during the 4 weeks
             preceding the administration of study drug and willing to continue with the diet while
             on study so as to avoid potential variability of response due to variations in dietary
             intake.

          9. In generally good health as evidenced by physical examination, clinical laboratory
             evaluations (hematology, chemistry, and urinalysis), and electrocardiogram (ECG) at
             Screening.

        Exclusion Criteria:

          1. 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.

          2. Use of any medication that is intended to treat PKU, including use of large amino
             acids, within 2 days prior to the administration of study drug.

          3. 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.

          4. A prior reaction that included systemic symptoms (eg, respiratory or gastrointestinal
             problems, hypotension, angioedema, anaphylaxis) to a PEG containing product. Patients
             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.

          5. Pregnant or breastfeeding at Screening or planning to become pregnant (self or
             partner) or to breastfeed at any time during the study.

          6. 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).

          7. Any condition that, in the view of the PI, places the patient at high risk of poor
             treatment compliance or of not completing the study.

          8. Alanine aminotransferase (ALT) concentration > 2 times the upper limit of normal.

          9. Creatinine > 1.5 times the upper limit of normal.

         10. A positive test for human immunodeficiency virus (HIV) antibody, hepatitis B surface
             antigen and hepatitis C antibody.