Phenylketonuria (PKU)Phase 3NCT03694353
Safety and Efficacy of Self Administered Injections of Pegvaliase (>40mg/Day Dose) in Adults With PKU
A Phase 3 study testing Pegvaliase in people with Phenylketonuria (PKU), run by BioMarin Pharmaceutical at 17 sites in United States.
Trial summary
This is a Phase 3 open-label extension study enrolling adult patients with PKU who were previously treated with pegvaliase in Studies PAL-003 (NCT00924703) or 165-302 (NCT02468570). The study is designed to evaluate the long-term safety and efficacy of pegvaliase administered at doses > 40 mg/day to 60 mg/day. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Phenylketonuria (PKU)
- What is being tested?
- Pegvaliase
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 17 sitesUnited States
- Study dates
- 13 Sep 2018to 13 Jan 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must be enrolled in PAL-003 or 165-302 Part 4 at the time of screening for 165-304 and most recently receiving pegvaliase at a dose > 40 mg/day.
- Has identified a competent person or persons ≥ 18 years of age who can observe the subject during study drug administration and for a minimum of 1 hour following administration in situations required per protocol.
- For females with childbearing potential, must have negative pregnancy test at screening and be willing to have additional pregnancy tests during the study.
- If sexually active and not planning to become pregnant (self or partner), must be willing to use 2 acceptable methods of contraception while participating in the study and for 4 weeks after the study.
- Is willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any research-related procedures; a legally authorized representative may provide written consent and assent may be requested.
- Is willing and able to comply with all study procedures.
- Is in generally good health, as evidenced by physical examination and/or clinical laboratory evaluations (hematology, chemistry, and urinalysis).
Who cannot join
- Use of any investigational product (except pegvaliase) or investigational medical device within 30 days prior to screening or requirement for any investigational agent prior to completion of all scheduled study assessments.
- Use of any medication (except pegvaliase) intended to treat PKU, including the use of large neutral amino acids, within 2 days prior to the administration of pegvaliase (Day 1).
- Use or planned use of any injectable drugs containing PEG (other than pegvaliase), including medroxyprogesterone injection, within 3 months prior to screening and during study participation.
- A history of organ transplantation or on chronic immunosuppressive therapy
- A history of substance abuse (as defined by the American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders [DSM]) in the past 12 months or current alcohol or drug abuse
- Current participation in the Kuvan® registry study (PKU Demographics, Outcomes and Safety [PKUDOS])
- Concurrent disease or condition that would interfere with study participation or safety (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease)
- Any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or terminating early from the study
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
United States17 sites
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
University of Missouri Health Care
Columbia, Missouri, 65201
Wayne State University, Center for Molecular Medicine and Genetics, Pediatrics and Pathology
Detroit, Michigan, 48201
University of Florida
Gainesville, Florida, 32610
University of Texas Health Science Center at Houston
Houston, Texas, 77030
Indiana CTSI Clinical Research Center
Indianapolis, Indiana, 46202
University of Kentucky Medical Center
Lexington, Kentucky, 40536
Medical College of Milwaukee
Milwaukee, Wisconsin, 53226
Morristown Medical Center
Morristown, New Jersey, 07960
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
University of Oklahoma Health Science Center
Oklahoma City, Oklahoma, 73104
University of Nebraska Medical Center
Omaha, Nebraska, 68198
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Oregon Health and Science University
Portland, Oregon, 97239
Washington University School of Medicine
St Louis, Missouri, 63110
University of South Florida
Tampa, Florida, 33606
About this study
Official title: An Open-label Extension Study to Evaluate the Safety and Efficacy of Subcutaneous Injections of Pegvaliase (> 40 mg/Day Dose) in Adults With Phenylketonuria
This is a Phase 3 open-label extension study enrolling adult patients with PKU who were previously treated with pegvaliase in Studies PAL-003 (NCT00924703) or 165-302 (NCT02468570). The study is designed to evaluate the long-term safety and efficacy of pegvaliase administered at doses > 40 mg/day to 60 mg/day.
Read the detailed description
Pegvaliase dosing will continue without interruption from Parent Study 165-302 (NCT02468570) or Parent Study PAL-003 (NCT00924703). Beginning on Day 1, subjects will receive the same dose and regimen of pegvaliase they were receiving in either 165-302 or PAL-003. A subject who reduces to a dose of 40 mg/day or lower for 32 consecutive weeks will be discontinued from study drug and withdrawn from the study as they will have the option to transition to commercial drug. Dose reductions may be performed if warranted due to AEs or hypophenylalaninemia. Dose increases to up to 60 mg/day may be performed per investigator discretion in consultation with the sponsor's medical monitor. Dosing will continue for approximately 121 weeks.
- Conditions
- Phenylketonuria (PKU)
- Being tested
- Pegvaliase
- 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 rAvPAL-PEG
40-60mg/day
| Study group | Role | What they receive |
|---|---|---|
| Pegvaliase | Experimental | Beginning on Day 1, subjects will receive the same dose and regimen of pegvaliase they were receiving in 165-302 or PAL-003 (pegvaliase dosing should continue without interruption from the previous study). Subsequent revisions to dosing regimens are allowed following consultation with the medical monitor. Receives: Drug: Pegvaliase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
A treatment-emergent AE was defined as any adverse event (AE) newly appearing or worsened in severity following initiation of study drug until 4 weeks after last dose of pegvaliase
Measured: Up to Day 741 (approximately Week 106)
Change in Blood Phe Concentration
Change in blood phenylalanine (Phe) concentration from Parent Study baseline (naïve/pretreatment).
Measured: The Outcome Measure Data Table below uses the 'analysis visit' as defined by the mapping rule in the SAP. The last Phe measurement was mapped to 'analysis visit' week 121. The actual date of the last Phe measurement was day 836 (approximately Week 119).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2018
- Study start13 Sep 2018
- Primary completion13 Jan 2021
- Study completion13 Jan 2021
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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, MD, Study director, BioMarin Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03694353
- Sponsor's protocol ID
- 165-304
- Status last verified
- Feb 2022
- First submitted
- 4 Sep 2018
- Last updated
- 17 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Harding CO, Whitehall KB, Lilienstein J, Sazova O, Lindstrom K, Levy DG, Burton BK. Long-term management strategies for pegvaliase use in phenylketonuria: Lessons learned from the phase-3 PRISM open-label extension study. Genet Med. 2025 Aug;27(8):101459. doi: 10.1016/j.gim.2025.101459. Epub 2025 May 20.
PubMed 40411344
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Extension Study to Evaluate the Safety and Efficacy of Subcutaneous Injections of Pegvaliase (> 40 mg/Day Dose) in Adults With Phenylketonuria
- ClinicalTrials.gov ID
- NCT03694353
- Acronym / sponsor ID
- 165-304
- Conditions
- Phenylketonuria (PKU)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- 13 Sep 2018 (actual)
- Primary completion
- 13 Jan 2021 (actual)
- Study completion
- 13 Jan 2021 (actual)
- First posted
- 3 Oct 2018 (actual)
- Results
- Posted 17 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 3 open-label extension study enrolling adult patients with PKU who were previously treated with pegvaliase in Studies PAL-003 (NCT00924703) or 165-302 (NCT02468570). The study is designed to evaluate the long-term safety and efficacy of pegvaliase administered at doses > 40 mg/day to 60 mg/day.
Detailed description
Pegvaliase dosing will continue without interruption from Parent Study 165-302 (NCT02468570) or Parent Study PAL-003 (NCT00924703). Beginning on Day 1, subjects will receive the same dose and regimen of pegvaliase they were receiving in either 165-302 or PAL-003. A subject who reduces to a dose of 40 mg/day or lower for 32 consecutive weeks will be discontinued from study drug and withdrawn from the study as they will have the option to transition to commercial drug. Dose reductions may be performed if warranted due to AEs or hypophenylalaninemia. Dose increases to up to 60 mg/day may be performed per investigator discretion in consultation with the sponsor's medical monitor. Dosing will continue for approximately 121 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pegvaliase | Experimental | Drug: PegvaliaseBeginning on Day 1, subjects will receive the same dose and regimen of pegvaliase they were receiving in 165-302 or PAL-003 (pegvaliase dosing should continue without interruption from the previous study). Subsequent revisions to dosing regimens are allowed following consultation with the medical monitor. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Must be enrolled in PAL-003 or 165-302 Part 4 at the time of screening for 165-304 and most recently receiving pegvaliase at a dose > 40 mg/day.
- Has identified a competent person or persons ≥ 18 years of age who can observe the subject during study drug administration and for a minimum of 1 hour following administration in situations required per protocol.
- For females with childbearing potential, must have negative pregnancy test at screening and be willing to have additional pregnancy tests during the study.
- If sexually active and not planning to become pregnant (self or partner), must be willing to use 2 acceptable methods of contraception while participating in the study and for 4 weeks after the study.
- Is willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any research-related procedures; a legally authorized representative may provide written consent and assent may be requested.
Key exclusion criteria (8 listed)
- Use of any investigational product (except pegvaliase) or investigational medical device within 30 days prior to screening or requirement for any investigational agent prior to completion of all scheduled study assessments.
- Use of any medication (except pegvaliase) intended to treat PKU, including the use of large neutral amino acids, within 2 days prior to the administration of pegvaliase (Day 1).
- Use or planned use of any injectable drugs containing PEG (other than pegvaliase), including medroxyprogesterone injection, within 3 months prior to screening and during study participation.
- A history of organ transplantation or on chronic immunosuppressive therapy
- A history of substance abuse (as defined by the American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders [DSM]) in the past 12 months or current alcohol or drug abuse
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PegvaliaseAlso: rAvPAL-PEG40-60mg/day | Drug | Pegvaliase |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0
Time frame: Up to Day 741 (approximately Week 106)
A treatment-emergent AE was defined as any adverse event (AE) newly appearing or worsened in severity following initiation of study drug until 4 weeks after last dose of pegvaliase
Change in Blood Phe Concentration
Time frame: The Outcome Measure Data Table below uses the 'analysis visit' as defined by the mapping rule in the SAP. The last Phe measurement was mapped to 'analysis visit' week 121. The actual date of the last Phe measurement was day 836 (approximately Week 119).
Change in blood phenylalanine (Phe) concentration from Parent Study baseline (naïve/pretreatment).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40411344Harding CO, Whitehall KB, Lilienstein J, Sazova O, Lindstrom K, Levy DG, Burton BK. Long-term management strategies for pegvaliase use in phenylketonuria: Lessons learned from the phase-3 PRISM open-label extension study. Genet Med. 2025 Aug;27(8):101459. doi: 10.1016/j.gim.2025.101459. Epub 2025 May 20.
Related trials for Phenylketonuria (PKU)
RecruitingPhase 1
A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
Phenylketonuria
RecruitingPhase 2
A Study of MZE782 in Adults With PKU
Phenylketonuria (PKU)
RecruitingPhase 3
A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
Phenylketonuria
Recruiting
Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
Carrier of Phenylketonuria, Healthy
RecruitingPhase 3
A Study of JNT-517 in Participants With Phenylketonuria (PKU)
Phenylketonuria
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director, MD study director
BioMarin Pharmaceutical
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pegvaliase in people with Phenylketonuria (PKU), run by BioMarin Pharmaceutical at 17 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) as Assessed by CTCAE v5.0 (time frame: Up to Day 741 (approximately Week 106)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03694353, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2022.