Safety and Efficacy of Self Administered Injections of Pegvaliase (>40mg/Day Dose) in Adults With PKU

NCT03694353 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 165-304
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 17

Brief Summary

This is a Phase 3 open-label extension study enrolling adult patients with PKU who were previously treated with pegvaliase in Studies PAL-003 (NCT00924703) or 165-302 (NCT02468570). The study is designed to evaluate the long-term safety and efficacy of pegvaliase administered at doses \> 40 mg/day to 60 mg/day.

Conditions

Phenylketonuria (PKU)

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0

  A treatment-emergent AE was defined as any adverse event (AE) newly appearing or worsened in severity following initiation of study drug until 4 weeks after last dose of pegvaliase

  Up to Day 741 (approximately Week 106)

• Change in Blood Phe Concentration

  Change in blood phenylalanine (Phe) concentration from Parent Study baseline (naïve/pretreatment).

  The Outcome Measure Data Table below uses the 'analysis visit' as defined by the mapping rule in the SAP. The last Phe measurement was mapped to 'analysis visit' week 121. The actual date of the last Phe measurement was day 836 (approximately Week 119).

Study Arms (1)

Pegvaliase

EXPERIMENTAL

Beginning on Day 1, subjects will receive the same dose and regimen of pegvaliase they were receiving in 165-302 or PAL-003 (pegvaliase dosing should continue without interruption from the previous study). Subsequent revisions to dosing regimens are allowed following consultation with the medical monitor.

Drug: Pegvaliase

Interventions

Pegvaliase DRUG

40-60mg/day

Also known as: rAvPAL-PEG

Pegvaliase

Eligibility Criteria

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

You may qualify if:

• Must be enrolled in PAL-003 or 165-302 Part 4 at the time of screening for 165-304 and most recently receiving pegvaliase at a dose \> 40 mg/day.
• Has identified a competent person or persons ≥ 18 years of age who can observe the subject during study drug administration and for a minimum of 1 hour following administration in situations required per protocol.
• For females with childbearing potential, must have negative pregnancy test at screening and be willing to have additional pregnancy tests during the study.
• If sexually active and not planning to become pregnant (self or partner), must be willing to use 2 acceptable methods of contraception while participating in the study and for 4 weeks after the study.
• Is 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; a legally authorized representative may provide written consent and assent may be requested.
• Is willing and able to comply with all study procedures.
• Is in generally good health, as evidenced by physical examination and/or clinical laboratory evaluations (hematology, chemistry, and urinalysis).

You may not qualify if:

• Use of any investigational product (except pegvaliase) 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 pegvaliase) intended to treat PKU, including the use of large neutral amino acids, within 2 days prior to the administration of pegvaliase (Day 1).
• Use or planned use of any injectable drugs containing PEG (other than pegvaliase), including medroxyprogesterone injection, within 3 months prior to screening and during study participation.
• A history of organ transplantation or on chronic immunosuppressive therapy
• A history of substance abuse (as defined by the American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders \[DSM\]) in the past 12 months or current alcohol or drug abuse
• Current participation in the Kuvan® registry study (PKU Demographics, Outcomes and Safety \[PKUDOS\])
• 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)
• 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

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (17)

University of Florida

Gainesville, Florida, 32610, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Indiana CTSI Clinical Research Center

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky Medical Center

Lexington, Kentucky, 40536, United States

Location

Wayne State University, Center for Molecular Medicine and Genetics, Pediatrics and Pathology

Detroit, Michigan, 48201, United States

Location

University of Missouri Health Care

Columbia, Missouri, 65201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07960, United States

Location

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Medical College of Milwaukee

Milwaukee, Wisconsin, 53226, United States

Location

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: Debra Lounsbury/Sr. Director, Clinical Sciences
• Organization: BioMarin Pharmaceutical Inc

Dlounsbury@bmrn.com

415-506-6348

Study Officials

• Medical Director, 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: October 3, 2018
• Study Start: September 13, 2018
• Primary Completion: January 13, 2021
• Study Completion: January 13, 2021
• Last Updated: February 17, 2022
• Results First Posted: February 17, 2022

Record last verified: 2022-02

Locations

US (17)