165-301

Overview

Status: Recruiting
Keywords: PKU , Phenylketonuria , PEG-PAL
IRB Number: 00064283
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics

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 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 (naïve). 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.
 
OBJECTIVES:
 
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

Principal Investigator: Nicola Longo
Department: Pediatric Genetics
Co Investigator: Dave Viskochil
Co Investigator: Ashley Warnock
Co Investigator: Lorenzo Botto

Contact Information

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

Inclusion Criteria

• A current diagnosis of PKU with the following

o Current blood Phe concentration > 600 μmol/L at screening and
o 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 years of age and ≤ 70 years of age at the time of screening.
If taking Kuvan® treatment, have a treatment end date ≥ 14 days prior to Day 1 (ie, first dose of BMN 165).
• 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.
• Has identified a person who is ≥ 18 years of age who has the neurocognitive and linguistic capabilities to comprehend and complete the POMS-Observer-rated scale.
• Has identifed a competent person or persons who are ≥ 18 years of age who can observe the subject during study drug administration and for a minimum of 1 hour following administration until dose titration has completed and if needed upon return to dosing after an AE and per investigator determination. 
      A home healthcare nurse may perform the study drug observations. 
• 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. 
      o Males post vasectomy 2 years with no known pregnancies for at least 2 years do not need to use any          other forms of birth control during the study. 
      o 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 in accordance with Section 9.6.
• Have neurocognitive and linguistic capacities to comprehend and answer investigator's prompts for the  ADHD-RS IV scale and POMS scales.
• If applicable, maintained stable dose of medication for ADHD, depression, anxiety, or other psychiatric disorder for > 8 weeks prior to enrollment and willing to maintain stable dose throughout study unless a change is medically indicated.
• 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 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 that is intended to treat PKU (except Kuvan), including the use of large neutral amino acids, within 2 days prior to the administration of study drug (Day 1first dose of BMN 165). Note Kuvan treatment must be stopped > 14 days before day 1.
• 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.
• Known hypersensitivity to any components of BMN 165.
• Current use of levodopa.
• A positive test for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody.
• A history of organ transplantation or on chronic immunosuppressive therapy.
• A history of substance abuse (as defined by the Diagnostic and Statistical Manual of Mental Disorders [DSM IV]) in the past 12 months or current alcohol or drug abuse.
• current participant in the Kuvan registry study (PKU Demographics, Outcomes and Safety (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 (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.