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A Study to Evaluate the Safety and Efficacy of JNT-517 in Participants With Phenylketonuria (PKU)

Phase 3
Not yet recruiting
Conditions
Phenylketonuria
Interventions
Drug: JNT-517 Tablet
Registration Number
NCT06971731
Lead Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
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

Detailed Description

Not available

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
120
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 >45 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Drug: JNT-517 - 150 mg BID (Tablet)JNT-517 Tablet-
Drug: JNT-517 - 75 mg BID (Tablet)JNT-517 Tablet-
Primary Outcome Measures
NameTimeMethod
Percent change in plasma phenylalanine (Phe) levels from baseline to mean of Weeks 2, 4, and 6 in the JNT-517 150 mg BID dose groupBaseline visit to Week 6
Secondary Outcome Measures
NameTimeMethod
Participants achieving plasma Phe <600 μmol/L at end of Period 1 among those with baseline ≥600 μmol/L in the 150 mg BID and 75 mg BID groups, respectivelyBaseline visit to Week 6
Participants achieving plasma Phe levels <360 μmol/L at end of Period 1 in the 150 mg BID and 75 mg BID groups, respectivelyBaseline visit to Week 6
Change in plasma Phe from baseline to Weeks 2, 4, and 6 of Period 1 in the JNT-517 75 mg BID and 150 mg BID dose group, respectivelyBaseline visit to Week 6
Percent change in plasma Phe from baseline to mean of Weeks 2, 4, and 6 of Period 1 in the JNT-517 75 mg BID groupBaseline visit to Week 6
Participants achieving plasma Phe levels <120 μmol/L at end of Period 1 in the JNT-517 75 mg BID and 150 mg BID dose groups, respectivelyBaseline visit to Week 6

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