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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 February 2015 by BioMarin Pharmaceutical
Sponsor:
Information provided by (Responsible Party):
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01819727
First received: March 18, 2013
Last updated: February 27, 2015
Last verified: February 2015
  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 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.


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 With PKU Not Previously Treated With BMN 165

Resource links provided by NLM:


Further study details as provided by BioMarin Pharmaceutical:

Primary Outcome Measures:
  • safety and tolerability [ Time Frame: 1 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: 1 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: 1 to 36 weeks ] [ Designated as safety issue: Yes ]
    All patients will complete a 3-day diety diary to be submitted baseline (predose on Day 1), Week 4, and every 4 weeks thereafter. 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 will be evaluated on a monthly basis.


Estimated Enrollment: 300
Study Start Date: May 2013
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (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
  • rAvPAL-PEG
  • PEG-PAL
  • Pegvaliase
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
  • rAvPAL-PEG
  • PEG-PAL
  • Pegvaliase

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

    • Subjects who are < 18 years of age but are already enrolled into the study may continue to participate
  • 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
  • Has identified a person who is ≥ 18 years of age who has the neurocognitive and linguistic capacities to comprehend and complete the POMS-Observer-rated scale
  • Has identified 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 2 acceptable methods of contraception while participating in the study and 4 weeks after the study.

    • 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.
    • 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 dietician confirming that the subject is capable of maintaining their diet in accordance with dietary information presented in the protocol.
  • Have neurocognitive and linguistic capacities to comprehend and answer investigator's prompts for the 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 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
  • Creatinine >1.5 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

  Hide Study Locations
Locations
United States, California
University of California, San Diego School of Medicine Recruiting
La Jolla, California, United States, 92103
Contact: Nancy Tang    619-316-7538    n6tang@ucsd.edu   
Contact: Annette Feigenbaum    (619) 543-3565    afeigenbaum@ucsd.edu   
Principal Investigator: Annette Feigenbaum, MD         
Children's Hospital and Research Center Recruiting
Oakland, California, United States, 94609
Contact: Paul Harmatz, M.D.    510-428-3058    pharmatz@mail.cho.org   
Contact: Kaimiala Cardines    510-428-3885 ext 2098    kcardines@mail.cho.org   
Principal Investigator: Paul Harmatz, MD         
Children's Hospital of Orange County Not yet recruiting
Orange, California, United States, 92868
Contact: Nina Movsesyan    714-509-8475    nmovsesyan@choc.org   
Contact: Richard Chang, MD    714-289-4949    rchang@choc.org   
Principal Investigator: Richard Chang, MD         
United States, Colorado
The Children's Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Laurel Ware    720-777-5642    Laurel.Ware@childrenscolorado.org   
Contact: Janet Thomas, MD    303-724-2334    janet.thomas@childrenscolorado.org   
Principal Investigator: Janet Thomas, MD         
United States, Florida
University of Florida, Pediatrics Genetics & Metabolism Recruiting
Gainesville, Florida, United States, 32610
Contact: Christel Gross, RN    352-273-7763    grosscd@ufl.edu   
Contact: Roberto Zori, MD    352-294-5050    zorirt@peds.ufl   
Principal Investigator: Roberto Zori, MD         
University of Miami Health System Terminated
Miami, Florida, United States, 33136
University of South Florida Recruiting
Tampa, Florida, United States, 33606
Contact: Laurie Joughin    813-844-8153    ljoughin@tgh.org   
Contact: Amarillis Sanchez-Valle, MD    813-844-7829    asanche6@health.usf.edu   
Principal Investigator: Amarilis Sanchez-Valle, M.D.         
United States, Georgia
Emory Universty Not yet recruiting
Decatur, Georgia, United States, 30033
Contact: Eleanor Botha    404-778-8517    eleanor.botha@emoryhealthcare.org   
Contact: Hong Li    404-778-8529    Hong.li@emory.com   
Principal Investigator: Hong Li, MD         
United States, Illinois
Ann and Robert H Lurie Children's Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Barbara Burton, M.D.    312-227-6120    bburton@luriechildrens.org   
Contact: Rachel Katz    312-227-6764    rkatz@luriechildrens.org   
Principal Investigator: Barbara Burton, MD         
United States, Indiana
Riley Children's Hospital Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Susan Romie    317-278-6650    sromie@iu.edu   
Contact: Mary Stuy , MD    317-274-3966    mstuy@iu.edu   
Principal Investigator: Mary Stuy, MD         
United States, Kentucky
University of Kentucky Recruiting
Lexington, Kentucky, United States, 40536
Contact: Dianne Richeson    859-323-2093    Dianne.Richeson@uky.edu   
Contact: Stephen Amato, MD    859-323-0396    stephen.amato@uky.edu   
Principal Investigator: Stephen Amato, MD         
Weisskopf Child Evaluation Center / University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
Contact: Lauren Rayborn    502-629-7544    lauren.rayborn@louisville.edu   
Contact: Kara Goodin, MD    502-852-5334    kara.goodin@louisville.edu   
Principal Investigator: Kara Goodin, MD         
United States, Massachusetts
Children's Hospital Boston Recruiting
Boston, Massachusetts, United States, 02115
Contact: Vera Anastasoaie    617-355-7346    vera.anastasoaie@childrens.harvard.edu   
Contact: Harvey Levy, MD    617-355-6346    harvey.levy@childrens.harvard.edu   
Principal Investigator: Harvey Levy, MD         
United States, Michigan
Wayne State University Recruiting
Detroit, Michigan, United States, 48201
Contact: Linda Spencer    313-745-4513    LSpencer@dmc.org   
Contact: Robert Conway, MD    (313) 577-6298    tconway@med.wayne.edu   
Principal Investigator: Robert Conway, M.D.         
United States, Missouri
University of Missouri Recruiting
Columbia, Missouri, United States, 65212
Contact: Dawn Peck    573-884-5192    peckda@health.missouri.edu   
Contact: Esperanza Font-Montgomery, MD    573-882-6991    fontmontgomerye@health.missouri.edu   
Principal Investigator: Esperanza Font-Montgomery, MD         
Washington University Center for Applied Research Sciences Active, not recruiting
St. Louis, Missouri, United States, 63110
United States, Nebraska
Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Rachel Cooper    402-559-6256    rachel.cooper@unmc.edu   
Contact: William Rizzo, MD    402-559-2560    wrizzo@unmc.edu   
Principal Investigator: William Rizzo, MD         
United States, New Jersey
Cooper Health Systems Recruiting
Camden, New Jersey, United States, 08103
Contact: Sandy Corut    856-968-7366    corut-sandra@cooperhealth.edu   
Contact: Caroline Eggerding, MD    856-342-2226    eggerding.caroline@cooperhealth.edu   
Principal Investigator: Carolyn Eggerdng, M.D.         
Atlantic Health System - Morristown Medical Center Not yet recruiting
Morristown, New Jersey, United States, 07960
Contact: Christina Flora    973-971-6471    Christina.Flora@atlantichealth.org   
Contact: Darius Adams, MD    973524-1898    darius.adams@atlantichealth.org   
Principal Investigator: Darius Adams, MD         
United States, New York
Albany Medical College Recruiting
Albany, New York, United States, 12208
Contact: Cheryl Clow    518-262-5721    ClowC@mail.amc.edu   
Contact: Natasha Shur, MD    518-262-5120    shurn@mail.amc.edu   
Principal Investigator: Natasha Shur, MD         
Mount Sinai Medical Center Active, not recruiting
New York, New York, United States, 10029
University of Rochester Active, not recruiting
Rochester, New York, United States, 14642
United States, Ohio
University Hospital Cleveland, Case Medical Center Not yet recruiting
Cleveland, Ohio, United States, 94609
Contact: Cathy Tasi    216-844-3312    catherine.tasi@uhhospitals.org   
Contact: Jirair Bedoyan, MD    216-844-3936    jirair.bedoyan@uhhospitals.org   
Principal Investigator: Jirair Bedoyan, MD         
United States, Oklahoma
University of Oklahoma Recruiting
Oklahoma City, Oklahoma, United States, 73140
Contact: Ashley Ethriedge    405-271-8001    ashley-ethriedge@ouhsc.edu   
Contact: Klass Wierenga, MD    405-271-8685    klaas.wierenga@ouhsc.edu   
Principal Investigator: Klaas Wierenga, M.D.         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Cary O. Harding, MD    503-494-7608    hardingc@ohsu.edu   
Contact: Bettina Marrone    503-418-3620    marronet@ohsu.edu   
Principal Investigator: Cary O Harding, MD         
United States, Pennsylvania
St. Christopher's Hospital for Children Recruiting
Philadelphia, Pennsylvania, United States, 19134
Contact: Melissa Lech       msl46@drexelmed.edu   
Contact: Reena Jethva, MD    215-427-8372    rjethva@drexelmed.edu   
Principal Investigator: Reena Jethva, MD         
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Gerard Vockley, MD    412-692-7746    Gerard.Vockley@chp.edu   
Contact: Jessica Lindenberger, RN    412-692-7530    Jessica.lindenberger@chp.edu   
Principal Investigator: Gerard Vockley, MD         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Natalie Owen    615-322-7602    natalie.n.owen@vanderbilt.edu   
Contact: John Phillips, lll, MD    615-322-7601    john.a.phillips@vanderbilt.edu   
Principal Investigator: John Philips III, MD         
United States, Texas
University of Texas Houston Medical School Recruiting
Houston, Texas, United States, 77030
Contact: Joy Tomochek    713-500-5064    joy.tomochek@uth.tmc.edu   
Contact: Hope Northrup, MD    713-792-5330    hope.northrup@uth.tmc.edu   
Principal Investigator: Hope Northrup, M.D.         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Carrie Bailey    801-587-3605    carrie.bailey@hsc.utah.edu   
Contact: Nicola Longo, MD    801-585-2457    nicola.longo@hsc.utah.edu   
Principal Investigator: Nicola Longo, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98195
Contact: Jie Feng    215-616-7192    jief@uw.edu   
Contact: Ronald C Scott, MD    206-543-3370    crscott@u.washington.edu   
Principal Investigator: Ronald C Scott, MD         
United States, Wisconsin
Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Ashley Boerst    414-337-4210    ABoerst@mcw.edu   
Contact: David Dimmock, MD    414-266-2979    ddimmock@mcw.edu   
Principal Investigator: David Dimmock, M.D.         
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: February 27, 2015
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
Pegvaliase

ClinicalTrials.gov processed this record on March 03, 2015