Phenylketonuria
Conditions
Keywords
Phenylketonuria, PKU
Brief summary
The goal of this Phase 3, randomized study is to assess the safety, efficacy, tolerability, and pharmacokinetics (PK) of oral JNT-517 in adults (18 years of age or older) with PKU. Participants will receive either JNT-517 or placebo and will be blinded to their treatment assignment. Participants will have a 2 in 3 (or approximately 67%) chance of receiving JNT-517 during the first part of the study which will last approximately six weeks. During the second part of the study every participant who continues in the study will receive one of two doses of JNT-517 for an additional 46 weeks. The study requires a screening period of up to 35 days to ensure dietary stabilization and amino acid levels required to meet study eligibility. In total, participation in the study could last for up to 400 days. Participants will: Take 75 mg JNT-517 or 150 mg JNT-517, or a placebo BID (2x per day) for approximately 365 days; Visit the clinic or have a mobile health nurse visit your home for checkups and tests; Collect urine sample at home and bring to clinic on specified days; Keep a food diary 3 days before each study visit
Interventions
DRUGJNT-517 Tablet
JNT-517: 75 mg BID
Placebo Tablet: BID
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Males and females ≥18 years of age on Day 1 2. Clinical diagnosis of PKU 3. Average of at least 3 plasma Phe levels (after \>4-hour fast) during Screening period of ≥360 μmol/L 4. Not on pegvaliase within 4 weeks prior to Screening 5. If on sapropterin or large neutral amino acids, such as PheBloc®, NeoPhe®, and PreKunil® at Screening, must be on a stable dose 4 weeks prior to Screening and for the entire study duration. 6. Willing and able to maintain a stable diet in Phe and total protein (intact protein and medical food protein) and able to adjust diet through the duration of the study according to the Dietary Management Guidelines 7. Body weight \>40 kilograms (kg) 8. If biologically female of childbearing potential: 1. Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test by Day 1 2. Must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 highly effective contraceptive methods from Screening until at least 30 days after the last study drug administration 3. If taking estrogen- or progesterone-based oral contraceptives, must agree to use 2 other highly effective methods of contraception or must agree to sexual abstinence during the study 4. Must refrain from donating ova during the course of the study and for 30 days after the last dose of the study drug. 9. If a biologically female not of childbearing potential or postmenopausal, defined as follows: 1. Has had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) 2. Has had amenorrhea for minimum of 1 year with confirmation by levels of follicle stimulating hormone testing 3. 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 10. If biologically male, must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use highly effective contraceptive methods 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 biological 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. 11. Participants with psychiatric illness must be well-controlled for the last 6 months prior to the Screening visit and if on medication, on stable medications for the last 3 months. 12. Capable of giving signed informed consent or parent/legal guardian to provide informed consent and the participant to give assent and confirm able to comply with study procedures
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Absolute Change in Plasma Phenylalanine (Phe) From Baseline to the Mean of Weeks 2, 4, and 6 in the JNT-517 150 mg BID Dose Group at End of Period 1 | Baseline to End of Period 1 (Week 6) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Plasma Phe From Baseline to the Mean of Weeks 2, 4, and 6 in the JNT-517 150 mg BID Dose Group at End of Period 1 | Baseline to End of Period 1 (Week 6) | — |
| Percentage of Participants Achieving Plasma Phe <600 Micromoles per Liter (µmol/L) at End of Period 1 Among Participants With Baseline ≥600 µmol/L in the 150 mg BID and 75 mg BID Groups | Baseline to End of Period 1 (Week 6) | — |
| Percentage of Participants Achieving Plasma Phe <360 µmol/L at End of Period 1 in the 150 mg BID and 75 mg BID Groups | Baseline to End of Period 1 (Week 6) | — |
| Absolute Change in Plasma Phe From Baseline to the Mean of Weeks 2, 4, and 6 in the JNT-517 75 mg BID Group at End of Period 1 | Baseline to End of Period 1 (Week 6) | — |
| Percent Change in Plasma Phe From Baseline to the Mean of Weeks 2, 4, and 6 in the JNT-517 75 mg BID Group at End of Period 1 | Baseline to End of Period 1 (Week 6) | — |
| Change From Baseline in ADHD Rating Scale-5 (ADHD-RS-5) Inattentive Subscore in Participants With Baseline Inattentive Subscore >9 in the JNT-517 150 mg BID and 75 mg BID dose Groups at End of Period 1 | Baseline to End of Period 1 (Week 6) | The ADHD Rating Scale-5 (ADHD-RS-5) Inattentive Subscore (sum of 9 inattentive items) ranges from 0 to 27, with higher scores indicating greater severity of inattentive symptoms. A decrease in the subscore represents an improvement in symptoms. |
| Change From Baseline in Dietary Phe Intake While Achieving Plasma Phe <360 µmol/L | Baseline to End of Period 1 (Week 6) | — |
| Number of Participants With Treatment-Emergent Adverse Events and Serious Treatment-Emergent Adverse Events | From first dose of the study drug through Week 56 | — |
| Percentage of Participants With ≥30% and ≥50% Reduction From Baseline in Plasma Phe at Week 6 | Baseline to End of Period 1 (Week 6) | — |
| Percentage of Participants Achieving Plasma Phe <120 µmol/L at End of Period 1 in the 150 mg BID and 75 mg BID Groups | End of Period 1 (Week 6) | — |
| Absolute Change in Plasma Phe From Baseline to Weeks 2, 4, and 6 of Period 1 in the JNT-517 150 mg BID and 75 mg BID Groups | Baseline to End of Period 1 (Week 6) | — |
| Percent Change in Plasma Phe From Baseline to Weeks 2, 4, and 6 of Period 1 in the JNT-517 150 mg BID and 75 mg BID Groups | Baseline to End of Period 1 (Week 6) | — |
| Percentage of Participants Achieving Plasma Phe <600 µmol/L Among Participants With Baseline ≥600 µmol/L in the JNT-517 150 mg BID and 75 mg BID Dose Groups at the End of Period 2 | Baseline to End of Period 2 (Week 52) | — |
| Percentage of Participants Achieving Plasma Phe <360 µmol/L in the JNT-517 150 mg BID and 75 mg BID Dose Groups at the End of Period 2 | End of Period 2 (Week 52) | — |
| Percentage of Participants Achieving Plasma Phe <120 µmol/L in the JNT-517 150 mg BID and 75 mg BID Dose Groups at the End of Period 2 | End of Period 2 (Week 52) | — |
| Absolute Change From Baseline in Plasma Phe in the JNT-517 75 mg BID and 150 mg BID Dose Groups During Period 2 | Baseline to End of Period 2 (Week 52) | — |
| Percent Change From Baseline in Plasma Phe in the JNT-517 75 mg BID and 150 mg BID Dose Groups During Period 2 | Baseline to End of Period 2 (Week 52) | — |
| Percentage of Participants With ≥30% and ≥50% Reduction From Baseline in Plasma Phe During Period 2 | Baseline to End of Period 2 (Week 52) | — |
| Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Stop Signal Reaction Time at End of Period 1 | Baseline to End of Period 1 (Week 6) | The CANTAB Stop Signal Task measures response inhibition. Stop Signal Reaction Time (SSRT) reflects the time required to inhibit a response, with longer times indicating poorer inhibitory control. A decrease from baseline indicates improvement. |
| Change From Baseline in CANTAB Stop Signal Reaction Time During Period 2 | Baseline to End of Period 2 (Week 52) | The CANTAB Stop Signal Task measures response inhibition. SSRT reflects the time required to inhibit a response, with longer times indicating poorer inhibitory control. A decrease from baseline indicates improvement. |
| Change From Baseline in ADHD Rating Scale-5 (ADHD-RS-5) Inattentive Subscore in Participants with Baseline Inattentive Subscore >9 in the JNT-517 150 mg BID and 75 mg BID Dose Groups During Period 2 | Baseline to End of Period 2 (Week 52) | The ADHD Rating Scale-5 (ADHD-RS-5) Inattentive Subscore (sum of 9 inattentive items) ranges from 0 to 27, with higher scores indicating greater severity of inattentive symptoms. A decrease in the subscore represents an improvement in symptoms. |
| Change From Baseline in Dietary Protein Intake While Maintaining Plasma Phe <360 µmol/L | Baseline to End of Period 2 (Week 52) | — |
| Percentage of Participants Achieving Recommended Dietary Allowance (RDA) for Natural Intact Protein Intake While Maintaining Plasma Phenylalanine <360 µmol/L | End of Period 2 (Week 52) | — |
| Percentage of Participants Achieving Two Times the RDA for Natural Intact Protein Intake Consistent With an Unrestricted Diet While Maintaining Plasma Phenylalanine <360 µmol/L | End of Period 2 (Week 52) | — |
Countries
Australia, Canada, Czechia, France, Germany, Japan, Netherlands, Poland, Spain, United States
Contacts
CONTACTOtsuka Call Center
Outcome results
None listed