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NCT Number: NCT05270837

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Phenylketonuria (PKU) Amino Acid Metabolism, Inborn Errors Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Nutritional and Metabolic Diseases Phenylketonurias

Age range

12 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Charité - Universitätsmedizin Berlin, Berlin, Germany

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Pegvaliase

Drug

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

Other names: PEG PAL, BMN 165

Diet only

Other

Diet Control

Primary outcomes

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

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

    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).

  2. Incidence of Treatment-emergent Adverse Events (Part 1)

    Time frame: Up to Week 73

    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).

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

    Time frame: Baseline (Day 1), Week 73

    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)

  4. Percentage of Participants With Positive PAL IgG Antibody

    Time frame: Baseline (Day 1), Week 73

    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)

  5. Percentage of Participants With Positive PAL IgM Antibody

    Time frame: Baseline (Day 1), Week 73

    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)

  6. Percentage of Participants With Positive PEG IgG Antibody

    Time frame: Baseline (Day 1), Week 73

    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)

  7. Percentage of Participants With Positive PEG IgM Antibody

    Time frame: Baseline (Day 1), Week 73

    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)

  8. Percentage of Participants With Positive Neutralizing Antibodies (NAb)

    Time frame: Baseline (Day 1), Week 73

    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)

Secondary outcomes

  1. 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

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

    The total dietary protein intake following 72 weeks on study is defined as the mean total dietary protein intake calculated from the 3-day diet diaries collected at Week 69 and Week 73 visits. Total dietary protein is measured in grams/kilogram (g/kg).

    Baseline total protein intake at Part 1 was defined as the mean total dietary protein intake calculated from the 3 separate 3-day diet diaries collected during Screening/Run-in (2) and Day 1 (1).

  2. 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

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

    The total dietary protein intake following 72 weeks on study is defined as the mean total dietary protein intake calculated from the 3-day diet diaries collected at Week 69 and Week 73 visits. Total dietary protein is measured in grams/kilogram (g/kg).

    Baseline total protein intake at Part 1 was defined as the mean total dietary protein intake calculated from the 3 separate 3-day diet diaries collected during Screening/Run-in (2) and Day 1 (1).

  3. Pegvaliase Tmax (Week 73 Intensive PK)

    Time frame: Week 73

    Time to maximum observed plasma concentration (Tmax) for pegvaliase during the Week 73 intensive PK assessment, defined as the elapsed time from dosing to the sampling time at which the highest observed pegvaliase plasma concentration (Cmax) occurs based on the Week 73 plasma concentration-time profile.

    Pharmacokinetic (PK)

  4. Pegvaliase Cmax (Week 73 Intensive PK)

    Time frame: Week 73

    Maximum observed plasma concentration (Cmax) of pegvaliase during the Week 73 intensive PK assessment, defined as the highest measured pegvaliase plasma concentration across the Week 73 postdose sampling interval. Cmax is summarized in ng/mL concentration units based on observed values from the Week 73 concentration-time profile.

  5. Pegvaliase AUC0-24 (Week 73 Intensive PK)

    Time frame: Week 73

    Area under the plasma concentration-time curve from 0-24 hours postdose (AUC0-24) for pegvaliase during the Week 73 intensive PK assessment. AUC0-24 was calculated form the Week 73 plasma concentration-time data using noncompartmental methods and reported in ng*h/mL units.

  6. Pegvaliase Cavg (Week 73 Intensive PK)

    Time frame: Week 73

    Average plasma concentration over the 0 to 24 hour postdose interval for pegvaliase during the Week 73 intensive PK assessment, reported in ng/mL concentration units, representing the mean pegvaliase exposure across the 24 hour postdose interval at Week 73.

  7. Overall: Incidence of Treatment-emergent Adverse Events (Including Part 2)

    Time frame: Up to Week 153

  8. Part 2: Percentage of Participants With Anti-pegvaliase Total Antibody (TAb), Positive PAL IgG Antibody, Positive PAL IgM Antibody, Positive PEG IgG Antibody, Positive PEG IgM Antibody and Positive Neutralizing Antibodies (NAb)

    Time frame: Baseline (Day 1), Week 145

  9. Part 2: Pegvaliase Tmax, Cmax, AUC0-24 and Cavg (Week 145 Intensive PK)

    Time frame: Week 145

Sponsors and collaborators

Lead sponsor

BioMarin Pharmaceutical

Industry

Registry information

Official study 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- Open-Label Randomized Two-Arm (Active vs Diet-Only Control)

Acronym: PEGASUS

Important dates

Study start
2022
Primary completion
2025
Study completion
2027
First posted
Mar 8, 2022
Registry last updated
Jul 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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