165-302

Overview

Status: Recruiting
Keywords: PKU , PEG-PAL
IRB Number: 00066308
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics

Brief Summary

BMN 165-302 is a three-part, Phase 3 study. Part 1 is an open-label run-in period designed to stabilize the dosing regimen of subjects who enroll from a previous BMN 165 study. Part 2 is a double-blind, placebo-controlled, four-arm, discontinuation study designed to compare the blood Phe concentrations of subjects who continue administration with BMN 165 versus those of subjects who temporarily receive placebo. Part 3 is a long-term, open-label extension study designed to evaluate the long-term efficacy and safety of BMN 165 and to provide long-term access to BMN 165. To better access long-term BMN 165 exposure, subjects prevented by dosing-limiting AEs from achieving a stable dose of 20 or 40 mg/day in Part 1 (3 to 12 weeks) may go directly from Part 1 to Part 3 (PK/PD and open-label extension). In addition, once 120 subjects are randomized in Part 2, subjects remaining in Part 1 may go directly to Part 3 at their current doses. During the open-label extension, dose may be increased to 60 mg/day at investigator discretion based on documented risk/benefit considerations. 

the provision outlined in Section 9.1.3 : PART 3: PK/PD and Long-Term Extension to increase subject dose to 60 mg/day in Part 3 is being suspended as of today, March 28, 2014. No subject's dose can be increased to 60 mg/day until further notice. Study 165-302 will continue with the other changes detailed in Amendment 1. The Federal Drug Administration (FDA) has requested that BioMarin provide safety and efficacy data in support of the option to administer 60 mg/day in subjects on 165-302.
 

OBJECTIVES: 

Part 1: Run-In Period 

The objective of Part 1 of this study is the following: 

• To evaluate the safety of BMN 165 (40 or 20 mg/day) in previously exposed subjects who self administer BMN 165 

Part 2: Blinded, Randomized, Discontinuation 

The primary efficacy objective of Part 2 of this study is the following: 

• To evaluate blood Phe concentration in previously exposed subjects who self administer BMN 165 (40 or 20 mg/day) compared with previously exposed subjects who self administer a placebo 

The secondary efficacy objective of Part 2 of this study is the following: 

• To evaluate cognitive and mood symptoms in subjects who self administer BMN 165 (40 or 20 mg/day) compared with previously exposed subjects who self administer a placebo 

The safety objective of Part 2 of this study is the following: 

• To evaluate the safety of BMN 165 in previously exposed subjects who self administer BMN 165 (40 or 20 mg/day) compared with previously exposed subjects who self administer a placebo 

The tertiary objectives of Part 2 of this study are the following: 

• To characterize the protein intake from medical food and from natural protein in subjects who self administer BMN 165 (40 or 20 mg/day) 

• To evaluate the trough plasma concentrations of BMN 165 in subjects who self administer BMN 165 (40 or 20 mg/day) 

Part 3: Long-Term Extension 

The objectives of Part 3 of this study are the following: 

• To evaluate the long-term effect of BMN 165 (40 mg/day) on blood Phe concentration in subjects who self administer BMN 165 

• To characterize long-term cognitive and mood symptoms in subjects who self administer BMN 165 (40 mg/day) 

 

 

Principal Investigator: Nicola Longo
Department: Pediatric Genetics
Co Investigator: Nicola Longo
Co Investigator: Sharon Ernst
Co Investigator: Krista Viau
Co Investigator: Chelsey Clegg
Co Investigator: Lorenzo Botto

Contact Information

Name:Carrie Bailey
Phone: 8015873605
Email: carrie.bailey@hsc.utah.edu

Inclusion Criteria

 

Have completed ≥ 14 weeks of administration with BMN 165 prior to screening. 

• Have had a stable BMN 165 dose regimen for ≥ 28 days prior to screening. 

• Are ≥ 18 years of age and ≤ 70 years of age at the time of screening. 

• 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. 

• Are willing and able to comply with all study procedures. 

• For females of childbearing potential, must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study. (Females are considered not of childbearing potential if they 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.) 

• If sexually active, must be willing to use two acceptable methods of contraception while participating in the study. 

• Have maintained their diet (including medical formula) with no significant modifications during the 4 weeks prior to randomization and are willing to maintain their current diet and, if needed, adjust their dietary and/or medical food protein intake according to the study protocol. 

• Have cognitive and linguistic capacities to complete the cognitive and mood scales. 

• Are in generally good health, as evidenced by physical examination, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and ECG tests performed at screening. 

 

 

Exclusion Criteria

 

Use of any investigational product (with the exception of 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 other than BMN 165 that is intended to treat PKU, including the use of large neutral amino acids, within 2 days prior to the administration of study drug (Day 1 [ie, first dose of BMN 165]). 

• Have known hypersensitivity to Dextran® or components of Dextran®. 

• Use or planned use of any injectable drugs containing PEG (other than 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 (subjects who participated in Study PAL-003 only). 

• A history of organ transplantation or on chronic immunosuppressive therapy. 

• A history of substance abuse (as defined by the DSM IV) in the past 12 months or current alcohol or drug abuse. 

• Have initiated or adjusted medication for treatment of ADHD, depression, or anxiety ≤ 8 weeks prior to enrollment. 

• 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 (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease). 

• 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 > 2 times the upper limit of normal. 

• Creatinine > 1.5 times the upper limit of normal. 

To preclude study subjects from participating in more than one PKU study simultaneously, subjects enrolled in the BioMarin-sponsored Kuvan registry study are ineligible for this study.