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

NCT05270837 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 1 other identifier: 165-306
• Study Type: interventional
• Target: 55
• Locations: 2 countries
• Sites: 16

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.

Conditions

Phenylketonuria (PKU)

Keywords

PKU; BioMarin; Phenylketonuria; BMN165; PAL; Subcutaneous Injections; Pegvaliase; adolescent PKU

Outcome Measures

Primary Outcomes (8)

• Change From Baseline in Blood Phe Concentration Following 72 Weeks (Average of the Week 69 and Week 73) on Study.

  The blood Phe measurement following 72 weeks on study is defined as the average of the Week 69 and Week 73 blood Phe measurements. Change from baseline in blood Phe will be compared between participants in the active (pegvaliase) and the control (diet-only) treatment arms. Baseline blood Phe concentration at Part 1 was defined as the average of 3 pre-treatment measurements collected between Screening/Run-in (2) and Day 1 pre-dose (1).

  Baseline to Week 72 (average of the Week 69 and Week 73)

• Incidence of Treatment-emergent Adverse Events (Part 1)

  Treatment-emergent adverse events (TEAE) is defined as any AE that newly appeared or worsened in severity after first dose of pegvaliase (pegvaliase arm) or on or after study day 1 (diet-only arm) until 30 days after last dose of the study. Serious adverse event (SAE).

  Up to Week 73

• Percentage of Participants With Positive Anti-pegvaliase Total Antibody (TAb)

  The anti-pegvaliase total antibody (TAb) method captures drug-binding antibodies comprised of different isotypes and specificities. Antibody Positivity = number of subjects testing positive at any study visit / total number of subjects at study visit. The baseline was defined as the last non-missing measurement collected prior to the first pegvaliase dose (pegvaliase arm) or prior to or on Visit 1 date (diet-only arm)

  Baseline (Day 1), Week 73

• Percentage of Participants With Positive PAL IgG Antibody

  The presence of immunoglobulin G (IgG) Antibodies against phenylalanine ammonia lyase (PAL) is measured overtime. The baseline was defined as the last non-missing measurement collected prior to the first pegvaliase dose (pegvaliase arm) or prior to or on Visit 1 date (diet-only arm)

  Baseline (Day 1), Week 73

• Percentage of Participants With Positive PAL IgM Antibody

  The presence of immunoglobulin M (IgM) Antibodies against PAL (phenylalanine ammonia lyase) is measured overtime. PAL IgM was positive if the titer value was greater than or equal to the median of all baseline PAL IgM titers. The baseline was defined as the last non-missing measurement collected prior to the first pegvaliase dose (pegvaliase arm) or prior to or on Visit 1 date (diet-only arm)

  Baseline (Day 1), Week 73

• Percentage of Participants With Positive PEG IgG Antibody

  The presence of IgG Antibodies against polyethylene glycol (PEG) is measured overtime The baseline was defined as the last non-missing measurement collected prior to the first pegvaliase dose (pegvaliase arm) or prior to or on Visit 1 date (diet-only arm)

  Baseline (Day 1), Week 73

• Percentage of Participants With Positive PEG IgM Antibody

  The presence of IgM Antibodies against PEG (polyethylene glycol) is measured overtime The baseline was defined as the last non-missing measurement collected prior to the first pegvaliase dose (pegvaliase arm) or prior to or on Visit 1 date (diet-only arm)

  Baseline (Day 1), Week 73

• Percentage of Participants With Positive Neutralizing Antibodies (NAb)

  Neutralizing antibodies (NAbs) capable of inhibiting the enzymatic activity of pegvaliase were measured. The baseline was defined as the last non-missing measurement collected prior to the first pegvaliase dose (pegvaliase arm) or prior to or on Visit 1 date (diet-only arm)

  Baseline (Day 1), Week 73

Secondary Outcomes (9)

• Change From Baseline in Total Dietary Protein Intake (i.e., Medical Food and/or Intact Food) Following 72 Weeks (Average of Week 69 and Week 73) on Study

  Baseline to Week 72 (average of Week 69 and week 73)

• Percentage Change From Baseline in Total Dietary Protein Intake (i.e., Medical Food and/or Intact Food) Following 72 Weeks (Average of Week 69 and Week 73) on Study

  Baseline to Week 72 (average of Week 69 and week 73)

• Pegvaliase Tmax (Week 73 Intensive PK)

  Week 73

• Pegvaliase Cmax (Week 73 Intensive PK)

  Week 73

• Pegvaliase AUC0-24 (Week 73 Intensive PK)

  Week 73

Study Arms (2)

Pegvaliase

EXPERIMENTAL

Treatment Arm

Drug: Pegvaliase

Diet Only

OTHER

Participants will be managing their PKU with diet alone. Participants in the diet-only control arm will be required to maintain and adjust dietary and medical protein food intake through Week 72, initiating pegvaliase treatment beginning Week 73 and, from Weeks 73 through 215.

Other: Diet Only

Interventions

Pegvaliase DRUG

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

Also known as: PEG PAL, BMN 165

Pegvaliase

Diet Only OTHER

Diet Control

Diet Only

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (16)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Children's Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

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

Chicago, Illinois, 60611, United States

Location

IU Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

University of Kentucky College of Medicine

Lexington, Kentucky, 40506, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States

Location

McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth)

Houston, Texas, 77030, United States

Location

University of Utah Medical Center

Salt Lake City, Utah, 84132, United States

Location

University of Virginia School of Medicine

Charlottesville, Virginia, 22903, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, Germany

Location

Universitat Mainz

Mainz, Germany

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: Thomas Machnig, Senior Medical Director
• Organization: BioMarin Pharmaceutical Inc.

thomas.machnig@bmrn.com

+44 207 4203405

Study Officials

• Study Director

  BioMarin Pharmaceutical

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2022
• First Posted: March 8, 2022
• Study Start: June 17, 2022
• Primary Completion: January 14, 2025
• Study Completion (Estimated): October 1, 2027
• Last Updated: July 21, 2026
• Results First Posted: July 21, 2026

Record last verified: 2026-06

Locations

US (13); DE (3)