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

NCT ID: NCT03694353

Last Updated: 2022-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-13
• Study Completion Date: 2021-01-13

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.

Detailed Description

Pegvaliase dosing will continue without interruption from Parent Study 165-302 (NCT02468570) or Parent Study PAL-003 (NCT00924703). Beginning on Day 1, subjects will receive the same dose and regimen of pegvaliase they were receiving in either 165-302 or PAL-003. A subject who reduces to a dose of 40 mg/day or lower for 32 consecutive weeks will be discontinued from study drug and withdrawn from the study as they will have the option to transition to commercial drug. Dose reductions may be performed if warranted due to AEs or hypophenylalaninemia. Dose increases to up to 60 mg/day may be performed per investigator discretion in consultation with the sponsor's medical monitor. Dosing will continue for approximately 121 weeks.

Conditions

Phenylketonuria (PKU)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pegvaliase

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.

Group Type: EXPERIMENTAL

Pegvaliase

Intervention Type: DRUG

40-60mg/day

Interventions

Pegvaliase

40-60mg/day

Intervention Type: DRUG

Other Intervention Names

rAvPAL-PEG

Eligibility Criteria

Inclusion Criteria

• 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).

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioMarin Pharmaceutical

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director, MD

Role: STUDY_DIRECTOR

BioMarin Pharmaceutical

Locations

University of Florida

Gainesville, Florida, United States

University of South Florida

Tampa, Florida, United States

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

Chicago, Illinois, United States

Indiana CTSI Clinical Research Center

Indianapolis, Indiana, United States

University of Kentucky Medical Center

Lexington, Kentucky, United States

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

Detroit, Michigan, United States

University of Missouri Health Care

Columbia, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Morristown Medical Center

Morristown, New Jersey, United States

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, United States

Oregon Health and Science University

Portland, Oregon, United States

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

University of Texas Health Science Center at Houston

Houston, Texas, United States

Medical College of Milwaukee

Milwaukee, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

165-304

Identifier Type: -

Identifier Source: org_study_id