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An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165

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Disease Information

Descriptive Information
Brief Title † An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165
Official Title † A Phase 3, Open-Label, Randomized, Multi-Center Study to Assess the Safety & Tolerability of an Induction, Titration, and Maintenance Dose Regimen of BMN 165 Self Administered by Adults With PKU Not Previously Treated With BMN 165
Brief 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 patients 18 to 70 years old with hyperphenylalaninemia due to PKU. Study BMN 165-301 is a Phase 3, open-label, randomized study designed to further characterize the safety of BMN 165 during two induction, titration, and maintenance dose regimens in adults with PKU who have not had previous exposure to BMN 165 (naive). Subjects will be randomized (1:1) to titrate up to one of two dose regimens. Other key features of this study are the dose regimens chosen for induction and titration; the study duration; self administration of study drug; and the chosen tertiary objectives.
Detailed Description Primary and Secondary Outcomes: The primary objective of the study is the following: - To characterize the safety and tolerability during induction, titration, and maintenance dosing in BMN 165-naïve subjects who self administer BMN 165 at dose levels of 20 mg/day and 40 mg/day The secondary objective of the study is the following: - To evaluate blood Phe concentration during induction, titration, and maintenance dosing in BMN 165-naïve subjects who self administer BMN 165 at dose levels of 20 mg/day and 40 mg/day The tertiary objectives of the study are the following: - To characterize the protein intake from medical food and from natural protein in BMN 165-naïve subjects administered BMN 165 at dose levels of 20 mg/day and 40 mg/day - To characterize baseline ADHD-like symptoms in BMN 165-naïve subjects - To evaluate trough plasma concentrations of BMN 165 in BMN 165-naïve subjects administered BMN 165 at dose levels of 20 mg/day and 40 mg/day Primary Analysis: All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). The incidence of AEs will be summarized by system organ class, preferred term, relationship to study drug, and severity for the subjects who are randomized to the 40 mg/day dose, the 20 mg/day dose, and overall. A by-subject listing will be provided for those subjects who experience an SAE, including death, or experience an AE associated with early withdrawal from the study or study drug. Hypersensitivity AEs and AEs that result in dosing interruption or dose reduction are of interest, and the percentage of subjects who report these AEs will be presented. Clinical laboratory data will be summarized by the type of laboratory test for the subjects who are randomized to the 40 mg/day dose, the 20 mg /day dose, and overall. Frequency and percentage of subjects who experience abnormal (ie, outside of reference range) and/or clinically significant abnormalities after study drug administration will be presented for each clinical laboratory test. For each clinical laboratory test, descriptive statistics will be provided for baseline and all subsequent post-baseline visits. Changes from baseline to the post-baseline visits will also be provided. Descriptive statistics, including clinically significant changes from baseline, of vital signs, physical examination results, ECG test results, and immunogenicity test results will also be provided in a similar manner. Additionally, antibodies and titers will be summarized at the scheduled time point. Detailed statistical methods will be provided in the Statistical Analysis Plan (SAP). Secondary Analysis: The secondary efficacy endpoint is change from baseline to end of study in blood Phe concentration. Baseline is defined as the average of blood Phe concentrations collected prior to dosing at the Screening Visit and on Day 1. The primary analysis method for the secondary endpoint will use a repeated measures model, with change from baseline Phe as the dependent variable and dose (40 mg/day or 20 mg/day), study week, and baseline Phe as independent variables. A responder analysis will be presented as a cumulative distribution function. The percentage of subjects with blood Phe concentration below "X" umol/L at the end of the study will be plotted and summarized for various "X" as a cumulative distribution function for each of the 2 doses and overall. Detailed statistical methods will be provided in the SAP. Tertiary Analyses: The statistical analysis method for tertiary endpoints (protein intake; the ADHD-RS IV score) will be descriptive. More details regarding the analysis methods for the tertiary endpoints will be provided in the SAP. Trough plasma concentrations of BMN 165 will be evaluated. DMC The Data Monitoring Committee (DMC) will act in an advisory capacity to BioMarin to monitor subject safety and the efficacy of BMN 165 in subjects who participate in Study BMN 165-301 .The DMC responsibilities may include the following: - Review the study protocol, informed consent and assent documents, and plans for data monitoring - Evaluate the progress of the trial; study data quality; timeliness; subject recruitment, accrual and retention; subjects' risk versus benefit; and other factors that could affect the study outcome - Consider relevant information that may have an effect on the safety of the participants or the ethics of the study - Protect the safety of the study participants in accordance with the stopping rules as defined in study protocol - Make recommendations to BioMarin concerning continuation or termination of the study or other modifications of the study based on their observations - If appropriate, conduct interim analysis of safety and efficacy
Study Phase Phase 3
Study Type † Interventional
Study Design †
Primary Outcome Measure † safety and tolerability
Secondary Outcome Measure † blood phe concentration
Condition † Phenylketonuria
Intervention † DrugBMN 165
Study Arms / Comparison Groups BMN 165, 20mg/day Subjects who meet the eligibility criteria will be randomized 1:1 to titrate to one of two dose regimens: 20 mg/day or 40 mg/day. The randomization will be stratified by the last available blood Phe concentration prior to Day 1 (600 to 900 μmol/L and > 900 μmol/L). BMN 165, 40mg/day Subjects who meet the eligibility criteria will be randomized 1:1 to titrate to one of two dose regimens: 20 mg/day or 40 mg/day. The randomization will be stratified by the last available blood Phe concentration prior to Day 1 (600 to 900 μmol/L and > 900 μmol/L).
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 261
Start Date † May 2013
Completion Date December 2016
Primary Completion Date November 2015
Eligibility Criteria † INCLUSION CRITERIA Individuals eligible to participate in this study must meet all of the following criteria: - A current diagnosis of PKU with the following: - Current blood Phe concentration >600 µmol/L at screening and - Average blood Phe concentration of >600 µmol/L over the past 6 months (per available data) - Have no previous exposure to BMN 165 - Are ≥18 and ≤70 years of age at the time of screening - Subjects who are 2 times the upper limit of normal - Creatinine >1.5 times the upper limit of normal.
Gender All
Ages 18 Years - 70 Years
Accepts Healthy Volunteers No
Contacts ††
Location Countries † United States
Administrative Information
NCT ID † NCT01819727
Organization ID 165-301
Secondary IDs †† Prism301
Responsible Party Sponsor
Study Sponsor † BioMarin Pharmaceutical
Collaborators ††
Investigators † Study Director: Markus Merilainen, MD, BioMarin Pharmaceutical
Information Provided By
Verification Date January 2017
First Received Date † March 18, 2013
Last Updated Date January 30, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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