Phenylketonuria (PKU)Phase 3NCT06628128
A Long-Term Study of JNT-517 in Participants With Phenylketonuria
A Phase 3 study testing JNT-517 in people with Phenylketonuria (PKU), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 12 sites in 2 countries.
Trial summary
The goal of this Phase 3, open-label study is to evaluate the long-term safety of JNT-517 in pediatric and adult participants with Phenylketonuria (PKU) after completion of either Study JNT517-101 (NCT05781399) or JNT517-201 (NCT06637514) as well as participants who have not participated in a prior JNT-517 study. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Phenylketonuria (PKU)
- What is being tested?
- JNT-517
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 11 Aug 2025to 1 Feb 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of phenylketonuria (ie, PAH deficiency) by either molecular testing or biochemical criteria consistent with the applicable regional guidelines.
- Participants 4 years of age and older, inclusive, at time of Screening.
- Not on pegvaliase within 4 weeks of Screening.
- Not on sepiapterin within 2 weeks of Screening.
- If on sapropterin or large neutral amino acids at Screening, must be on a stable dose for 4 weeks prior to Screening.
- Willing and able to maintain a diet consistent in Phe content from the Screening period through the duration of the study, unless otherwise directed by a dietician as allowed in the protocol.
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- Body weight ≥ 12.5 kg.
- If female of childbearing potential:
- Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test by Day 1.
- Must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 method must be highly effective, from Screening until at least 30 days after the last study drug administration.
- Must refrain from donating ova during the course of the study and for 30 days after the last dose of the study drug.
- Is a female not of childbearing potential or postmenopausal, defined as follows:
- Has had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).
- Has had amenorrhea for minimum of 1 year with confirmation by levels of follicle stimulating hormone testing.
- Has not achieved menarche (has not had first menstrual period). If a female achieves menarche during the study, she will need to follow the contraception requirement for females of childbearing potential.
- If male, must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 method must be highly effective, from Day 1 until at least 30 days after the last study drug administration and must refrain from donating sperm during the course of the study and for 30 days after the last dose of the study drug.
- Note: No restrictions are required for males who have undergone a documented vasectomy at least 4 months prior to Screening. If the vasectomy procedure is not documented or was performed less than 4 months prior to Screening, males must follow the same contraception as for non-vasectomized participants.
- Capable of giving signed informed consent, or parent/legal guardian to provide informed consent and pediatric participant to give assent, and be able to comply with study procedures.
- Participants with psychiatric illness must be well-controlled for the last 3 months prior to screening visit and, if on medication, on stable medications for the last 3 months.
Who cannot join
- Participation in this study is not considered safe and/or feasible in the opinion of the Investigator.
- Participants have not completed a previous JNT-517 study and are eligible for another active JNT-517 trial at the site, unless approval is obtained from the medical monitor.
- Any acute or chronic medical condition that would prevent the participant from complying with the procedures or place the participant at risk if they participate in the study.
- Positive for hepatitis B or C or human immunodeficiency virus.
- Any history of significant liver disease.
- Any history of cataracts or more than minimal cataracts observed during the Screening ophthalmologic examination.
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- Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.
- Estimated glomerular filtration rate < 60 milliliters per minute per 1.73 square meters (mL/min/1.73 m^2) by 2021 Chronic Kidney Disease Epidemiology Collaboration formula (participants aged 17 years or greater) or by Schwartz formula (participants aged 4 to 16 years of age).
- History of drug or alcohol abuse in the last year.
- Use of any medication that are inhibitors or inducers of cytochrome P450 (CYP)3A4 or inhibitors of the transporter P glycoprotein (P-gp) within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration.
- Use of any medications that are a substrate of breast cancer resistance protein (BCRP), multidrug and toxin extrusion (MATE)1, MATE2-K, organic anion transporter 3 (OAT3), or CYP3A4 within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration (Appendix A). CYP3A4 substrates may be allowed if reduction in exposure is not expected to impact safety of the participant after consultation with the Medical Monitor.
- NOTE: Participants of childbearing potential will be permitted to continue with estrogen- or progesterone based oral contraceptives, but must agree to use 2 other methods of contraception, where at least 1 must be highly effective, or must agree to sexual abstinence during the study.
- Current, recent, or suspected infection within 2 weeks of Screening of Severe Acute Respiratory Syndrome Coronavirus 2/Coronavirus Disease 2019 (SARS-CoV-2/COVID-19).
- Unable to tolerate oral medication or inability to swallow tablets.
- Allergy to JNT-517 or any component of the investigational product.
- Any of the following laboratory values at the Screening visit:
- Alanine aminotransferase or aspartate aminotransferase values ˃ 1.5 x the upper limit of normal (ULN).
- Total bilirubin ˃ULN unless history of Gilbert Syndrome and then total bilirubin >4 milligrams per deciliter [mg/dL] is exclusionary.
- Hemoglobin ˂10.0 g/dL (˂100.0 grams per liter [g/L])
- White blood cell count ˃1 x ULN
- Platelet count ˂150 × 109/L (˂150,000/cubic millimeters[mm^3])
- Participation in another investigational drug trial within 30 days (other than for JNT-517) or, if known 5 half-lives of investigational drug (whichever is longer).
Trial locations and contacts
12 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
12 sites in 2 countries
United States8 sites, 8 recruiting
- Recruiting
Children's Medical Center Dallas
Dallas, Texas, 75235
Otsuka Call Center, 844-687-8522, Otsuka-ProfessionalServices@otsuka-us.com
McNutt
- Recruiting
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Otsuka Call Center, 844-687-8522, Otsuka-ProfessionalServices@otsuka-us.com
McNutt
- Recruiting
University of Florida (UF) Health Shands Hospital
Gainesville, Florida, 32608
Otsuka Call Center, 844-687-8522, Otsuka-ProfessionalServices@otsuka-us.com
Zori
- Recruiting
University of Texas Health (UTHealth) Science Center at Houston
Houston, Texas, 77030
Otsuka Call Center, 844-687-8522, Otsuka-ProfessionalServices@otsuka-us.com
Northrup
- Recruiting
University of Pittsburgh Medical Center (UPMC) - Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Otsuka Call Center, 844-687-8522, Otsuka-ProfessionalServices@otsuka-us.com
Vockley
- Recruiting
Oregon Health and Science University
Portland, Oregon, 97239
Otsuka Call Center, 844-687-8522, Otsuka-ProfessionalServices@otsuka-us.com
Harding
- Recruiting
Utah Health - The University of Utah Hospital
Salt Lake City, Utah, 84112
Otsuka Call Center, 844-687-8522, Otsuka-ProfessionalServices@otsuka-us.com
Andrews
- Recruiting
University of South Florida
Tampa, Florida, 33606
Otsuka Call Center, 844-687-8522, Otsuka-ProfessionalServices@otsuka-us.com
Sanchez-Valle
Australia4 sites, 4 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Otsuka Call Center, 844-687-8522, Otsuka-ProfessionalServices@otsuka-us.com
Bratkovic
- Recruiting
Murdoch Children's Research Institute
Parkville, Victoria, 3052
Otsuka Call Center, 844-687-8522, Otsuka-ProfessionalServices@otsuka-us.com
Peters
- Recruiting
Children's Health Queensland - Queensland Children's Hospital
South Brisbane, Queensland, 4101
Otsuka Call Center, 844-687-8522, Otsuka-ProfessionalServices@otsuka-us.com
Inwood
- Recruiting
Mater Health - Mater Hospital Brisbane
South Brisbane, Queensland, 4101
Otsuka Call Center, 844-687-8522, Otsuka-ProfessionalServices@otsuka-us.com
Nisbet
About this study
Official title: An Open-Label Study to Evaluate the Long-Term Safety of JNT-517 in Participants With Phenylketonuria
The goal of this Phase 3, open-label study is to evaluate the long-term safety of JNT-517 in pediatric and adult participants with Phenylketonuria (PKU) after completion of either Study JNT517-101 (NCT05781399) or JNT517-201 (NCT06637514) as well as participants who have not participated in a prior JNT-517 study. In this trial, all participants will receive JNT-517 using age- and weight-banded dosing as outlined in the protocol, regardless of any dose received in a previous study.
- Conditions
- Phenylketonuria (PKU)
- Being tested
- JNT-517
- Keywords
- Phenylketonuria, PKU
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JNT-517Drug
JNT-517 administered orally twice daily using age- and weight-banded dosing.
| Study group | Role | What they receive |
|---|---|---|
| JNT-517 | Experimental | Not described Receives: Drug: JNT-517 |
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)
Reported based on results of 12-lead electrocardiograms (ECGs), vital signs, clinical laboratory tests, and other medical assessments.
Measured: Screening to +2 weeks from last dose
Secondary outcomes (11)
Absolute Change from Baseline in Plasma Phe
Measured: Baseline to +2 weeks from last dose
Percent Change from Baseline Over Time in Plasma Phe
Measured: Baseline to +2 weeks from last dose
Percentage of Participants with Plasma Phe <600 micromoles (µM) Over Time in Participants with Baseline Phe >600 µM
Measured: Baseline to +2 weeks from last dose
Percentage of Participants with Plasma Phe ≤360 µM Over Time in Participants with Baseline Phe >360 µM
Measured: Baseline to +2 weeks from last dose
Percentage of Participants with Plasma Phe ≥120 µM Over Time in Participants with Baseline Phe >120 µM
Measured: Baseline to +2 weeks from last dose
Change from Baseline Over Time in Urinary Phe and Other Amino Acids
Measured: Baseline to +2 weeks from last dose
Absolute Change from Baseline Over Time in Dietary Phe Intake
Absolute change from baseline over time in dietary Phe intake (milligrams per kilogram per day [mg/kg/day]) for participants achieving plasma Phe ≤360 μM
Measured: Baseline to +2 weeks from last dose
Absolute Change from Baseline Over Time in Dietary Intact Protein Intake (grams per kilogram per day [g/kg/day]) for Participants Achieving Plasma Phe ≤360 μM
Measured: Baseline to +2 weeks from last dose
Percentage of Participants who Increase Phe Intake Over Time While Maintaining Plasma Phe ≤360 μM
Measured: Baseline to +2 weeks from last dose
Absolute Change from Baseline Over Time in the Attention-Deficit/Hyperactivity Disorder Rating Scale Version 5 (ADHD-RS-5) in Pediatric Participants who Previously Participated in JNT517-301
Measured: Month 6, Month 12, and yearly thereafter up to approximately 5 years
Plasma Concentrations Over Time in de novo Participants Aged 4 to 11 Years
Measured: Day 1 (1-hour postdose), and predose and 1-hour postdose on Day 7 and Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2024
- Study start11 Aug 2025
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Phenylketonuria (PKU)Studies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The 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
- 240 participants (estimated)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06628128
- Sponsor's protocol ID
- JNT517-501
- Other IDs
- 359-201-00006, 1013577, 2025-524753-13-00, 2025
- Status last verified
- Apr 2026
- First submitted
- 2 Oct 2024
- Last updated
- 1 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Study to Evaluate the Long-Term Safety of JNT-517 in Participants With Phenylketonuria
- ClinicalTrials.gov ID
- NCT06628128
- Acronym / sponsor ID
- JNT517-501
- Conditions
- Phenylketonuria (PKU)
- Keywords
- Phenylketonuria, PKU
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Aug 2025 (actual)
- Primary completion
- 1 Nov 2027 (estimated)
- Study completion
- 1 Feb 2028 (estimated)
- First posted
- 4 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this Phase 3, open-label study is to evaluate the long-term safety of JNT-517 in pediatric and adult participants with Phenylketonuria (PKU) after completion of either Study JNT517-101 (NCT05781399) or JNT517-201 (NCT06637514) as well as participants who have not participated in a prior JNT-517 study. In this trial, all participants will receive JNT-517 using age- and weight-banded dosing as outlined in the protocol, regardless of any dose received in a previous study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| JNT-517 | Experimental | Drug: JNT-517 |
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (19 listed)
- Diagnosis of phenylketonuria (ie, PAH deficiency) by either molecular testing or biochemical criteria consistent with the applicable regional guidelines.
- Participants 4 years of age and older, inclusive, at time of Screening.
- Not on pegvaliase within 4 weeks of Screening.
- Not on sepiapterin within 2 weeks of Screening.
- If on sapropterin or large neutral amino acids at Screening, must be on a stable dose for 4 weeks prior to Screening.
Key exclusion criteria (22 listed)
- Participation in this study is not considered safe and/or feasible in the opinion of the Investigator.
- Participants have not completed a previous JNT-517 study and are eligible for another active JNT-517 trial at the site, unless approval is obtained from the medical monitor.
- Any acute or chronic medical condition that would prevent the participant from complying with the procedures or place the participant at risk if they participate in the study.
- Positive for hepatitis B or C or human immunodeficiency virus.
- Any history of significant liver disease.
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 |
|---|---|---|
| JNT-517JNT-517 administered orally twice daily using age- and weight-banded dosing. | Drug | JNT-517 |
Primary outcome
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Time frame: Screening to +2 weeks from last dose
Reported based on results of 12-lead electrocardiograms (ECGs), vital signs, clinical laboratory tests, and other medical assessments.
11 secondary outcomes
Absolute Change from Baseline in Plasma Phe
Time frame: Baseline to +2 weeks from last dose
Percent Change from Baseline Over Time in Plasma Phe
Time frame: Baseline to +2 weeks from last dose
Percentage of Participants with Plasma Phe <600 micromoles (µM) Over Time in Participants with Baseline Phe >600 µM
Time frame: Baseline to +2 weeks from last dose
Percentage of Participants with Plasma Phe ≤360 µM Over Time in Participants with Baseline Phe >360 µM
Time frame: Baseline to +2 weeks from last dose
Percentage of Participants with Plasma Phe ≥120 µM Over Time in Participants with Baseline Phe >120 µM
Time frame: Baseline to +2 weeks from last dose
Change from Baseline Over Time in Urinary Phe and Other Amino Acids
Time frame: Baseline to +2 weeks from last dose
Absolute Change from Baseline Over Time in Dietary Phe Intake
Time frame: Baseline to +2 weeks from last dose
Absolute Change from Baseline Over Time in Dietary Intact Protein Intake (grams per kilogram per day [g/kg/day]) for Participants Achieving Plasma Phe ≤360 μM
Time frame: Baseline to +2 weeks from last dose
Percentage of Participants who Increase Phe Intake Over Time While Maintaining Plasma Phe ≤360 μM
Time frame: Baseline to +2 weeks from last dose
Absolute Change from Baseline Over Time in the Attention-Deficit/Hyperactivity Disorder Rating Scale Version 5 (ADHD-RS-5) in Pediatric Participants who Previously Participated in JNT517-301
Time frame: Month 6, Month 12, and yearly thereafter up to approximately 5 years
Plasma Concentrations Over Time in de novo Participants Aged 4 to 11 Years
Time frame: Day 1 (1-hour postdose), and predose and 1-hour postdose on Day 7 and Day 14
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- Otsuka Clinical Trial WebsiteLink provided by the sponsor.
- Otsuka Clinical Trial TransparencyLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
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Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
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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.
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing JNT-517 in people with Phenylketonuria (PKU), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 12 sites in 2 countries.
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 19 inclusion and 22 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: looking for participants now, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Australia. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Otsuka Call Center (844-687-8522, otsuka-professionalservices@otsuka-us.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Treatment-emergent Adverse Events (TEAEs) (time frame: Screening to +2 weeks from last dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 May 2026.