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

NCT01819727 | Completed Phase 3 Results DMC

• 2 other identifiers: 165-301Prism301
• Study Type: interventional
• Target: 261
• Locations: 1 country
• Sites: 31

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.

Conditions

Phenylketonuria

Keywords

PKU; PEG-PAL; BioMarin; rAv-PAL PEG; BMN 165; open label; Prism301; Pegvaliase

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Hypersensitivity Adverse Reaction

  Hypersensitivity AEs will be identified in two ways: * Broad Algorithmic anaphylactic reaction Standardized MedDRA Queries (SMQ) * Modified Hypersensitivity SMQ to include above additional preferred terms

  baseline and 36 weeks

Secondary Outcomes (1)

• Blood Phenylalanine Concentration

  baseline and 36 weeks

Other Outcomes (1)

• Dietary Phenylalanine

  baseline and 36 weeks

Study Arms (2)

BMN 165, 20mg/day

ACTIVE COMPARATOR

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

BMN 165, 40mg/day

ACTIVE COMPARATOR

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

Interventions

BMN 165 DRUG

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 (Weeks 5 up to 34) 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 amount of time it takes to reach a dose regimen of 20 mg/day with no dose interruptions) and up to 30 weeks (accounts for dose reduction or interruption due to AEs). Subjects will stop titration once they have achieved either the 20 mg/day or 40 mg/day dose regimen. The majority of subjects will maintain the 20 or 40 mg/day dose regimen for at least an additional 2 weeks until a minimum of approximately 26 weeks or a maximum of 36 weeks in the study.

Also known as: rAvPAL-PEG, Pegvaliase

BMN 165, 20mg/day; BMN 165, 40mg/day

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (31)

University of California, Altman Clinical and Translational Research Institute

La Jolla, California, 92037, United States

Location

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

The Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Florida Clinical Research Center

Gainesville, Florida, 32610, United States

Location

University of Miami Health System

Miami, Florida, 33136, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Emory Universty

Decatur, Georgia, 30033, United States

Location

Ann and Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Riley Children's Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

Weisskopf Child Evaluation Center / University of Louisville

Louisville, Kentucky, 40202, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

University of Missouri

Columbia, Missouri, 65212, United States

Location

Washington University Center for Applied Research Sciences

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Cooper Health Systems

Camden, New Jersey, 08103, United States

Location

Atlantic Health System - Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Icahn School of Medicine at Mount Sinai Medical Center

New York, New York, 10029, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

University Hospital Cleveland, Case Medical Center

Cleveland, Ohio, 44106, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Health Science at Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Bilder DA, Arnold GL, Dimmock D, Grant ML, Janzen D, Longo N, Nguyen-Driver M, Jurecki E, Merilainen M, Amato G, Waisbren S. Improved attention linked to sustained phenylalanine reduction in adults with early-treated phenylketonuria. Am J Med Genet A. 2022 Mar;188(3):768-778. doi: 10.1002/ajmg.a.62574. Epub 2021 Nov 26.

  PMID: 34826353 DERIVED

Related Links

• Biomarin Pharmaceutical website
• BioMarin sponsored PKU educational/community website

MeSH Terms

Conditions

Phenylketonurias

Interventions

pegvaliase

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Principal Scientist I, Clinical Sciences
• Organization: BioMarin Pharmaceutical Inc.

dlounsbury@bmrn.com

415-506-6348

Study Officials

• Markus Merilainen, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: All subjects receive Study Drug. Subjects will be randomized (1:1) to titrate up to one of two dose regimens: 20 mg/day or 40 mg/day.Eligible subjects will be randomized 1:1 using an IWRS to titrate to one of two dose regimens: 20 mg/day or 40 mg/day. The randomization will be stratified by blood Phe levels of 600 to 900 µmol/L and \>900 µmol/ using the last available blood Phe concentration prior to Day 1 of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2013
• First Posted: March 28, 2013
• Study Start: May 1, 2013
• Primary Completion: November 25, 2015
• Study Completion: November 25, 2015
• Last Updated: February 26, 2019
• Results First Posted: September 10, 2018

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (31)