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

• ClinicalTrials.gov Identifier: NCT05270837
• Recruitment Status: Active, not recruiting
• First Posted: March 8, 2022
• Last Update Posted: January 26, 2024
• Sponsor: BioMarin Pharmaceutical
• Information provided by (Responsible Party): BioMarin Pharmaceutical

Tracking Information

• First Submitted Date: February 1, 2022
• First Posted Date: March 8, 2022
• Last Update Posted Date: January 26, 2024
• Actual Study Start Date: June 17, 2022
• Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 25, 2022)

• Change in blood Phe concentration [ Time Frame: Treatment naïve baseline following 72 weeks on study ]
• Incidence of treatment-emergent adverse events as assessed by CTCAE v5.0 [ Time Frame: Treatment naïve baseline following 72 weeks on study ]

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: February 25, 2022): Change in total dietary protein intake [ Time Frame: Treatment naïve baseline following 72 weeks on study ]
• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: January 25, 2024)

• Characterize area under plasma concentration time curve (AUC) of pegvaliase [ Time Frame: Baseline to 215 weeks ]
• Characterize maximum plasma concentration (Cmax) of pegvaliase [ Time Frame: Baseline to 215 weeks ]
• Characterize trough plasma concentration (Ctrough) of pegvaliase [ Time Frame: Baseline to 215 weeks ]
• Characterize time to reach maximum plasma concentration (Tmax) of pegvaliase [ Time Frame: Baseline to 215 weeks ]

Original Other Pre-specified Outcome Measures (submitted: February 25, 2022)

• Characterize area under plasma concentration time curve (AUC) of pegvaliase [ Time Frame: Baseline to 153 weeks ]
• Characterize maximum plasma concentration (Cmax) of pegvaliase [ Time Frame: Baseline to 153 weeks ]
• Characterize trough plasma concentration (Ctrough) of pegvaliase [ Time Frame: Baseline to 153 weeks ]
• Characterize time to reach maximum plasma concentration (Tmax) of pegvaliase [ Time Frame: Baseline to 153 weeks ]

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Phenylketonuria (PKU)

Intervention

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

  • PEG PAL
  • BMN 165
• Other: Diet Only
  Diet Control

Study Arms

• Experimental: Pegvaliase
  Intervention: Drug: Pegvaliase
• Drug: Diet Only
  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.
  Intervention: Other: Diet Only

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: September 19, 2023): 55
• Original Estimated Enrollment (submitted: February 25, 2022): 54
• Estimated Study Completion Date: October 2027
• Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, United States

Administrative Information

• NCT Number: NCT05270837
• Other Study ID Numbers: 165-306
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: BioMarin Pharmaceutical
• Original Responsible Party: Same as current
• Current Study Sponsor: BioMarin Pharmaceutical
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Study Director; BioMarin Pharmaceutical

• PRS Account: BioMarin Pharmaceutical
• Verification Date: January 2024