An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165 (Prism301)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by BioMarin Pharmaceutical
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01819727
First received: March 18, 2013
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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 equal or greater than 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 (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.


Condition Intervention Phase
Phenylketonuria
Drug: BMN 165
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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 w/Phenylketonuria

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • safety and tolerability [ Time Frame: 14 to 36 weeks ] [ Designated as safety issue: Yes ]
    Assessments and procedures for safety and blood Phe concentration will be performed every 4 weeks throughout this study. Safety will be monitored throughout the study by assessment of vital signs, physical examination, electrocardiograms (ECGs), AEs, concomitant medications, and clinical laboratory tests (chemistry, hematology, and urinalysis).


Secondary Outcome Measures:
  • blood phe concentration [ Time Frame: 14 to 36 weeks ] [ Designated as safety issue: Yes ]
    Subjects will be assessed for plasma blood Phe concentration at baseline (predose on Day 1), Week 3, Week 4, and every 4 weeks thereafter.


Other Outcome Measures:
  • Metabolism [ Time Frame: 14-36 weeks ] [ Designated as safety issue: Yes ]
    All patients will complete a 3-day diety diary to be submitted monthly. Their dietary intake will be calculated and analyzed through a computer software program, "Metabolic Pro" The diary data will be analyzed by nutritional software for total kcals, protein, phe, tyrosine, and the percentage of DRI provided for protein, phe, tyrosine, vitamins, and minerals. Blood and urine tests for glucose, calcium, nitrogen and creatinine will be evaluated on a monthly basis.


Estimated Enrollment: 90
Study Start Date: May 2013
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 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).
Drug: BMN 165

After informed consent, eligible subjects will be randomized (1:1) to titrate up to one of two dose regimens: 20 mg/day or 40 mg/day. All subjects will initiate IP at a fixed-dose of 2.5 mg/week for 4 weeks (Induction).

After the Induction Period, subjects will enter the Titration Period (Week 5 up to Week 32) where they will increase their weekly BMN 165 dose to a daily dose regimen of 20 mg/day or 40 mg/day. The Titration Period will be individualized to each subject based on a minimum of 6 weeks (the time it takes to reach a dose regimen of 20 mg/day with no dose interruptions) and up to 28 weeks (accounts for dose interruptions due to AEs). Subjects will stop titration once they have achieved either the 20 mg/day or 40 mg/day dose. A maintenance dose will be administered for 4 weeks.

Other Names:
  • BMN 165
  • previously refered to as:
  • rAvPAL-PEG
  • PEG-PAL
Active Comparator: 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).
Drug: BMN 165

After informed consent, eligible subjects will be randomized (1:1) to titrate up to one of two dose regimens: 20 mg/day or 40 mg/day. All subjects will initiate IP at a fixed-dose of 2.5 mg/week for 4 weeks (Induction).

After the Induction Period, subjects will enter the Titration Period (Week 5 up to Week 32) where they will increase their weekly BMN 165 dose to a daily dose regimen of 20 mg/day or 40 mg/day. The Titration Period will be individualized to each subject based on a minimum of 6 weeks (the time it takes to reach a dose regimen of 20 mg/day with no dose interruptions) and up to 28 weeks (accounts for dose interruptions due to AEs). Subjects will stop titration once they have achieved either the 20 mg/day or 40 mg/day dose. A maintenance dose will be administered for 4 weeks.

Other Names:
  • BMN 165
  • previously refered to as:
  • rAvPAL-PEG
  • PEG-PAL

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ≥16 and ≤70 years of age at the time of screening
  • If taking Kuvan, 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
  • For females of childbearing potential, must have a negative pregnancy test at screening and be willing to have additional pregnancy tests during the study.
  • If sexually active, must be willing to use 2 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 enrollment 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 neurocognitive and linguistic capacities to complete ADHD-RS IV 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 and ECG tests performed 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 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 administration of study drug Day 1 (first 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 participation 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01819727

Contacts
Contact: Jeri Williams 415-506-6444 jwilliams@bmrn.com

  Show 38 Study Locations
Sponsors and Collaborators
BioMarin Pharmaceutical
Investigators
Study Director: Markus Merilainen, MD BioMarin Pharmaceutical
  More Information

Additional Information:
No publications provided

Responsible Party: BioMarin Pharmaceutical
ClinicalTrials.gov Identifier: NCT01819727     History of Changes
Other Study ID Numbers: 165-301, Prism301
Study First Received: March 18, 2013
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by BioMarin Pharmaceutical:
PKU
PEG-PAL
BioMarin
rAv-PAL PEG
BMN 165
open label
Prism301

Additional relevant MeSH terms:
Phenylketonurias
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases

ClinicalTrials.gov processed this record on September 18, 2014