Phenylketonuria (PKU)Phase 3PEGASUSNCT05270837
Study to Evaluate the Safety and Efficacy of Pegvaliase in Adolescents (Ages 12-17) With Phenylketonuria
A Phase 3 study testing Pegvaliase and Diet Only in people with Phenylketonuria (PKU), run by BioMarin Pharmaceutical at 16 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 12 to 17 years
- Conditions the study is for
- Phenylketonuria (PKU)
- What is being tested?
- Pegvaliase and Diet Only
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 16 sitesin 2 countries
- Study dates
- 17 Jun 2022to Oct 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
16 sites in 2 countries.
16 sites in 2 countries
United States13 sites
Children's Hospital of Colorado
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
University of Virginia School of Medicine
Charlottesville, Virginia, 22903
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
McGovern Medical School, University of Texas Health Science Center at Houston (UTHealth)
Houston, Texas, 77030
IU Health University Hospital
Indianapolis, Indiana, 46202
University of Kentucky College of Medicine
Lexington, Kentucky, 40506
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Phoenix Children's Hospital
Phoenix, Arizona, 85016
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15224
University of Utah Medical Center
Salt Lake City, Utah, 84132
University of South Florida
Tampa, Florida, 33606
Germany3 sites
Charité - Universitätsmedizin Berlin
Berlin
Universitätsklinikum Hamburg-Eppendorf
Hamburg
Universitat Mainz
Mainz
About this study
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- Open-Label Randomized Two-Arm (Active vs Diet-Only Control)
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.
Read the 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.
- Conditions
- Phenylketonuria (PKU)
- Being tested
- Pegvaliase, Diet Only
- Keywords
- PKU, BioMarin, Phenylketonuria, BMN165, PAL, Subcutaneous Injections, Pegvaliase, adolescent PKU
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PegvaliaseDrug
Also called PEG PAL, BMN 165
Pegvaliase 2.5mg/10mg/20mg/40mg/60mg self-administered from 1 time up to 7 times a week
Diet OnlyOther
Diet Control
| Study group | Role | What they receive |
|---|---|---|
| Pegvaliase | Experimental | Treatment Arm Receives: 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. Receives: Other: Diet Only |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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).
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
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).
Measured: 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
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).
Measured: Baseline to Week 72 (average of Week 69 and week 73)
Pegvaliase Tmax (Week 73 Intensive PK)
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)
Measured: Week 73
Pegvaliase Cmax (Week 73 Intensive PK)
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.
Measured: Week 73
Pegvaliase AUC0-24 (Week 73 Intensive PK)
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.
Measured: Week 73
Pegvaliase Cavg (Week 73 Intensive PK)
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.
Measured: Week 73
Overall: Incidence of Treatment-emergent Adverse Events (Including Part 2)
Measured: Up to Week 153
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)
Measured: Baseline (Day 1), Week 145
Part 2: Pegvaliase Tmax, Cmax, AUC0-24 and Cavg (Week 145 Intensive PK)
Measured: Week 145
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2022
- Study start17 Jun 2022
- Primary completion14 Jan 2025
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Phenylketonuria (PKU)Studies of the same condition, open and under way.
- More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study chair, BioMarin Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05270837
- Sponsor's protocol ID
- 165-306
- Acronym
- PEGASUS
- Status last verified
- Jun 2026
- First submitted
- 1 Feb 2022
- Last updated
- 21 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No