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

Phenylketonuria (PKU) Clinical Trial

Official title:

An Open-label Extension Study to Evaluate the Safety and Efficacy of Subcutaneous Injections of Pegvaliase (> 40 mg/Day Dose) in Adults With Phenylketonuria

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03694353
• Other study ID #: 165-304
• Status: Completed
• Phase: Phase 3
• Start date: September 13, 2018
• Est. completion date: January 13, 2021

Study information

• Verified date: February 2022
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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A subject who reduces to a dose of 40 mg/day or lower for 32 consecutive weeks will be discontinued from study drug and withdrawn from the study as they will have the option to transition to commercial drug.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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: January 13, 2021
• Est. primary completion date: January 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Phenylketonuria (PKU)
• Phenylketonurias

Intervention

Drug:
• Pegvaliase
40-60mg/day

Locations

Country	Name	City	State
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University of Missouri Health Care	Columbia	Missouri
United States	Wayne State University, Center for Molecular Medicine and Genetics, Pediatrics and Pathology	Detroit	Michigan
United States	University of Florida	Gainesville	Florida
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	Indiana CTSI Clinical Research Center	Indianapolis	Indiana
United States	University of Kentucky Medical Center	Lexington	Kentucky
United States	Medical College of Milwaukee	Milwaukee	Wisconsin
United States	Morristown Medical Center	Morristown	New Jersey
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Oklahoma Health Science Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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).