Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Injections of BMN165 by Adults With PKU
Condition: Phenylketonuria (PKU)
MeSH terms: Phenylketonurias
Intervention: BMN165 20mg/day; BMN165 40mg/day; Placebo
Intervention description: BMN165 20mg/day self-administered daily; BMN165 40mg/day self-administered daily; Non-drug placebo, self-administered daily
Intervention MeSH terms: Dextrans
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 215.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: PKU; PEG-PAL; Prism; BioMarin; rAvPAL-PEG; BMN165

Summary:

      The BMN 165 clinical development program has been designed to demonstrate the safety and
      efficacy of BMN 165 in reducing blood Phe concentrations in adults with PKU.
    

Eligibility criteria:

        INCLUSION CRITERIA

        Individuals eligible to participate in this study must meet all of the following criteria:

          -  Have completed a prior BMN 165 study (PAL-003, 165-205, or 165-301) prior to screening

          -  Have had a stable BMN 165 dose regimen for at least 14 days prior to screening

          -  Are at least 18 y/o and no older than 70 y/o at screening

               -  Subjects who are < 18 y/o and are already enrolled into Study 165-301 under
                  Amendment #1 (10JAN2014) may enroll into this study

          -  Has identified a person who is > 18 y/o who has the neurocognitive and linguistic
             capacities to comprehend and complete the Profile of Mood States (POMS)-Observer rated
             scale

          -  Has identified a competent person(s) > 18 y/o who can observe the subject during study
             drug administration at certain points in the study

               -  A home healthcare nurse may perform the study drug observations

          -  Are 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; for minors,
             parent or guardian provides written consent and assent may be requested

          -  Are willing and able to comply with all study procedures

          -  For females of childbearing potential, a negative pregnancy test at screening and
             willing to have additional pregnancy tests during the study

          -  If sexually active, willing to use two acceptable methods of contraception during and
             for 4 weeks after the study

               -  Males post vasectomy for 2 years with no known pregnancies do not need to use any
                  other forms of contraception during the study.

               -  Females who have been in menopause for at least 2 years, have had a tubal
                  ligation at least 1 year prior to screening, or have had a total hysterectomy do
                  not need to use any other forms of contraception during the study.

          -  Have received documented approval from a study dietitian confirming that the subject
             is capable of maintaining their diet

          -  Have neurocognitive and linguistic capacities to comprehend and answer investigator's
             prompts for the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS)
             Investigator rated instrument and to complete the POMS-Subject rated scale

          -  If applicable, maintained stable dose of medication for Attention Deficit
             Hyperactivity Disorder (ADHD), depression, anxiety, or other psychiatric disorder ≥8
             weeks prior to enrollment and willing to maintain stable dose throughout study unless
             a change is medically indicated

          -  General good health, as evidenced by physical examination, clinical laboratory
             evaluations, and ECG tests at screening

        Exclusion Criteria

        Individuals who meet any of the following exclusion criteria will not be eligible to
        participate in the study:

          -  Use of any investigational product (except BMN 165) 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 (except BMN 165) intended to treat PKU, including the use of
             large neutral amino acids, within 2 days prior to the administration of study drug

          -  Have known hypersensitivity to Dextran® or components of Dextran

          -  Use or planned use of any injectable drugs containing PEG (except for BMN 165),
             including medroxyprogesterone injection, within 3 months prior to screening and during
             study participation

          -  Current use of levodopa

          -  A positive test for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody

          -  A history of organ transplantation or taking chronic immunosuppressive therapy

          -  A history of substance abuse in the past 12 months or current alcohol or drug abuse

          -  Current participation in the Kuvan registry study (PKUDOS). Patients may discontinue
             the PKUDOS registry trial to allow enrollment in this study

          -  Pregnant or breastfeeding at screening or planning to become pregnant (self or
             partner) or breastfeed at any time during the study

          -  Concurrent disease or condition that would interfere with study participation or
             safety.

          -  Major surgery planned during the study period

          -  Any condition that in the view of the investigator, places the subject at high risk of
             poor treatment compliance or terminating early from the study

          -  Alanine aminotransferase (ALT) concentration at least 2x the upper limit of normal

          -  Creatinine at least 1.5x the upper limit of normal