Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Injections of BMN165 by Adults With PKU

Phenylketonuria (PKU) Clinical Trial

— Prism-2  

Official title:

A Four-Part, Phase 3, Randomized, Double-Blind, Placebo- Controlled, Four-Arm, Discontinuation Study to Evaluate the Efficacy and Safety of Subcutaneous Injections of BMN 165 Self-Administered by Adults With Phenylketonuria (PKU)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01889862
• Other study ID #: 165-302
• Status: Completed
• Phase: Phase 3
• Start date: July 29, 2013
• Est. completion date: February 5, 2019

Study information

• Verified date: April 2021
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

165-302 is a Phase 3, 4 Part, Randomized, Double-Blind, Placebo-Controlled, Discontinuation Study to Evaluate the Efficacy and Safety of Self Administered Subcutaneous Injections of BMN 165 by Adults With PKU.

This study is open only to adults who have been exposed to BMN165 in a previous study.

Study BMN 165-302 is a four-Part, Phase 3 study.

• Part 1: Open-label period

• Part 2: A Randomized, double-blind, placebo-controlled period of 8 weeks

• Part 3: Two sub-Parts to Part 3:- Part 3A - BMN 165 administered using vial and syringe during this open label period. Part 3B - BMN 165 administered using prefilled syringe during this open-label period.

• Part 4: A long-term, open-label extension period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 215
• Est. completion date: February 5, 2019
• Est. primary completion date: January 13, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Phenylketonuria (PKU)
• Phenylketonurias

Intervention

Drug:
• BMN165 20mg/day
BMN165 20mg/day self-administered daily
• BMN165 40mg/day
BMN165 40mg/day self-administered daily
• Placebo
Non-drug placebo, self-administered daily

Locations

Country	Name	City	State
United States	Albany Medical Center	Albany	New York
United States	Emory Universty, Department of Human Genetics, Division of Medical Genetics	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Cooper Health Systems	Camden	New Jersey
United States	Ann and Robert H Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	University of Missouri Health Center	Columbia	Missouri
United States	Wayne State University Clinical Research Center at the Mott Center	Detroit	Michigan
United States	University of Florida Clinical Research Center	Gainesville	Florida
United States	University of Texas Houston Medical School	Houston	Texas
United States	Indiana CTSI Clinical Research Center	Indianapolis	Indiana
United States	University of California, San Diego Clinical and Translational Research Institute	La Jolla	California
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	University of Louisville, Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Atlantic Health System - Morristown Medical Center	Morristown	New Jersey
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Icahn School of Medicine at Mount Sinai Medical Center	New York	New York
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Washington University Center for Applied Research Sciences	Saint Louis	Missouri
United States	University of Utah Hospital	Salt Lake City	Utah
United States	University of Washinton	Seattle	Washington
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2	Blood phe concentration in subjects previously exposed to BMN165 who were administered BMN165 20 or 40 mg/day compared with those who were administered a matching placebo.	At Part 2 baseline and change from baseline at Part 2 week 8
Secondary	Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2	Attention deficit hyperactivity disorder rating scale IV (ADHD RS-IV) is investigator-rated, 9-item, inattention subscale score ranges from 0 to 27, with higher scores indicative of a greater degree of impairment and a baseline score >9 indicative of a presence of symptoms.	At Part 2 baseline and change from baseline at Part 2 week 8
Secondary	Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4	The long term effect of multiple dose levels of BMN165 on blood phe concentration in subjects who are administered BMN165 using pre-filled syringes.	At Part 4 week 57, 105, 161, 209 and 249
Secondary	Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2	Phenylketonuria (PKU) Total Mood Disturbance (TMD) Profile of Mood States (POMS); PKU POMS TMD is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely).	At Part 2 baseline and change from baseline at Part 2 week 8
Secondary	Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2	PKU POMS confusion mood domain (referred to as the confusion subscale) is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely).	At Part 2 baseline and change from baseline at Part 2 week 8
Secondary	Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2	Full-length POMS TMD is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely).	At Part 2 baseline and change from baseline at Part 2 week 8

External Links

•   BioMarin sponsored PKU educational/community website