Study to Evaluate the Safety and Efficacy of Pegvaliase in Adolescents (Ages 12-17) With Phenylketonuria

Phenylketonuria (PKU) Clinical Trial

— PEGASUS  

Official title:

A Phase 3 Multi-Center Study to Evaluate the Safety and Efficacy of Subcutaneous Injections of Pegvaliase in Adolescent Subjects (Ages 12-17) With Phenylketonuria Featuring an Open-Label Randomized Two-Arm (Active vs Diet-Only Control) Design

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05270837
• Other study ID #: 165-306
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 17, 2022
• Est. completion date: October 2027

Study information

• Verified date: January 2024
• Source: BioMarin Pharmaceutical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 3 open-label randomized controlled study enrolling approximately 54 adolescents with PKU. The study is designed to assess the safety and efficacy of pegvaliase injections.

Description:

This Phase 3 multicenter study is designed to evaluate the safety and efficacy of pegvaliase administered daily to adolescents (ages 12 to 17 years old (US), inclusive, and 12 to 15 years old (EU), inclusive 12-17) with phenylketonuria (PKU). Participants will be randomized in a 2:1 ratio to the active (pegvaliase) and control (diet-only) treatment arms, respectively, with 36 participants receiving pegvaliase and 18 participants managing their PKU with diet alone.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 55
• Est. completion date: October 2027
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

Inclusion Criteria

• Is 12 to 17 years old (US), inclusive, or 12 to 15 years (EU), inclusive, at the start of the Screening/Run-in Period (Day -28).
• Diagnosis of PKU and failure to maintain recommended blood Phe levels on existing management (sapropterin dihydrochloride and Phe-restricted diet) demonstrated by 2 blood Phe concentration measurements > 600 µmol/L during the Screening/Run-in Period (7 to 10 days in between blood Phe assessments) and average blood Phe concentration > 600 µmol/L over the past 12 months (per available data).
• Willing and able to maintain and adjust dietary and medical protein food intake according to the study protocol under the supervision of a study dietician or adequately trained designee per investigator discretion during study participation.
• If on medication for ADHD, depression, or other psychiatric disorder, stable dose of medication for = 8 weeks prior to enrollment and willing to maintain stable dose unless a change is medically indicated.
• An adult (= 18 years of age) has been identified who is willing and competent to observe the participant during study drug administration and for a minimum of 1 hour following administration.
• Participants must be capable of giving signed informed consent
• If sexually active, male or female participants must not plan to become pregnant (self or partner) and must use 2 acceptable methods of contraception while participating in the study beginning at Screening and for 4 weeks after discontinuing study drug. Exclusion Criteria
• Previous treatment with pegvaliase.
• Use of any medication that is intended to treat PKU, including the use of large neutral amino acids, within 14 days prior to the administration of study drug on Day 1.
• Use or planned use of any injectable drugs containing polyethylene glycol (PEG; other than pegvaliase), including medroxyprogesterone injection, within 3 months prior to the start of Screening/Run-in and during study participation with the exception of COVID-19 vaccinations.
• A history of organ transplantation or on chronic immunosuppressive therapy.
• Use of any investigational product or investigational medical device within 30 days prior to Screening/Run-in or requirement for any investigational agent prior to completion of all scheduled study assessments.
• A positive test for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody.
• Alanine aminotransferase (ALT) concentration > 2 × the upper limit of normal (ULN).
• Creatinine > 1.5 × ULN.
• Inability to identify and/or communicate to others that the participant is experiencing symptoms of potential anaphylaxis due to cognitive impairment or other reasons.

Related Conditions & MeSH terms

• Phenylketonuria (PKU)
• Phenylketonurias

Intervention

Drug:
• Pegvaliase
Pegvaliase 2.5mg/10mg/20mg/40mg/60mg self-administered from 1 time up to 7 times a week

Other:
• Diet Only
Diet Control

Locations

Country	Name	City	State
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Universitat Mainz	Mainz
United States	Children's Hospital of Colorado	Aurora	Colorado
United States	Boston Children's Hospital	Boston	Massachusetts
United States	University of Virginia School of Medicine	Charlottesville	Virginia
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University of Florida (Gainesville)	Gainesville	Florida
United States	McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth)	Houston	Texas
United States	IU Health University Hospital	Indianapolis	Indiana
United States	University of Kentucky College of Medicine	Lexington	Kentucky
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	University of Utah Medical Center	Salt Lake City	Utah
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
BioMarin Pharmaceutical

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Characterize area under plasma concentration time curve (AUC) of pegvaliase		Baseline to 215 weeks
Other	Characterize maximum plasma concentration (Cmax) of pegvaliase		Baseline to 215 weeks
Other	Characterize trough plasma concentration (Ctrough) of pegvaliase		Baseline to 215 weeks
Other	Characterize time to reach maximum plasma concentration (Tmax) of pegvaliase		Baseline to 215 weeks
Primary	Change in blood Phe concentration		Treatment naïve baseline following 72 weeks on study
Primary	Incidence of treatment-emergent adverse events as assessed by CTCAE v5.0		Treatment naïve baseline following 72 weeks on study
Secondary	Change in total dietary protein intake		Treatment naïve baseline following 72 weeks on study