Clinical trial NCT05270837: Study to Evaluate the Safety and Efficacy of Pegvaliase in Adolescents (Ages 12-17) With Phenylketonuria
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Phenylketonuria (PKU)
Keywords: PKU
BioMarin
Phenylketonuria
BMN165
PAL
Subcutaneous Injections
Pegvaliase
adolescent PKU
Lead sponsor: BioMarin Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2022-03-08
Enrollment: 55
Sex: ALL
Minimum age (years): 12
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in blood Phe concentration
timeFrame: Treatment naïve baseline following 72 weeks on study
measure: Incidence of treatment-emergent adverse events as assessed by CTCAE v5.0
timeFrame: Treatment naïve baseline following 72 weeks on study
Secondary outcomes:
measure: Change in total dietary protein intake
timeFrame: Treatment naïve baseline following 72 weeks on study
Other outcomes:
measure: Characterize area under plasma concentration time curve (AUC) of pegvaliase
timeFrame: Baseline to 215 weeks
measure: Characterize maximum plasma concentration (Cmax) of pegvaliase
timeFrame: Baseline to 215 weeks
measure: Characterize trough plasma concentration (Ctrough) of pegvaliase
timeFrame: Baseline to 215 weeks
measure: Characterize time to reach maximum plasma concentration (Tmax) of pegvaliase
timeFrame: Baseline to 215 weeks
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Aurora
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: IU Health University Hospital
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky College of Medicine
state: Kentucky
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth)
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia School of Medicine
state: Virginia
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Mainz
country: Germany
facility: Universitat Mainz
Study officials:
affiliation: BioMarin Pharmaceutical
name: Study Director
role: STUDY_CHAIR
References: