NCT06971731招募中3 期
A Phase 3, Double-Blind, Randomized, Two-Period, Multicenter, Placebo-Controlled, Efficacy and Safety Study of JNT-517 for the Treatment of Participants With Phenylketonuria
Otsuka Pharmaceutical Development & Commercialization, Inc.26 个研究点 分布在 10 个国家目标入组 120 人开始时间: 2025年10月20日最近更新:
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 26
- 主要终点
- 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 group
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females ≥18 years of age on Day 1
- •Clinical diagnosis of PKU
- •Average of at least 3 plasma Phe levels (after >4-hour fast) during Screening period of ≥360 μmol/L
- •Not on pegvaliase within 4 weeks prior to Screening
- •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.
- •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
- •Body weight >40 kilograms (kg)
- •If biologically 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 highly effective contraceptive methods from Screening until at least 30 days after the last study drug administration
- •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
- •Must refrain from donating ova during the course of the study and for 30 days after the last dose of the study drug.
- •If a biologically 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 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.
- •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.
- •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
排除标准
- •Exclusion Criteria
- •Participants will be excluded from the study if any of the following criteria are met:
- •Any acute or uncontrolled 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 malignancy of any organ system (other than non-melanoma skin cancer or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
- •Any history of significant liver disease
- •Any history of cataracts or more than minimal cataracts observed during the Screening ophthalmologic examination. Minimal cataracts are defined as changes similar to lens opacities classification system III (LOCS III), lens grade C1, N1 or P1
- •Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion
- •Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 by 2021 Chronic Kidney Disease Epidemiology Collaboration formula
- •Participation in another investigational drug trial within 30 days or, if known, 5 half-lives of the investigational drug (whichever is longer). For gene therapy or editing trials, participants must have received the intervention >6 months prior to Screening visit and with stable plasma Phe in the past 2 months prior to Screening visit.
- •Alcohol consumption within 5 days of randomization and/or unwilling to limit to 1 alcoholic drink per day until after the 6-month study visit
- •History of drug/alcohol abuse in the last year
- •Use of any medications that are inhibitors or inducers of cytochrome P450 (CYP3A4) or inhibitors of the transporter P-glycoprotein (P-gp) within 4 weeks prior to randomization and unwilling and/or unable to avoid these medications throughout the treatment duration
- •Use of any medications that are substrates of breast cancer resistance protein (BCRP), multidrug and toxin extrusion (MATE)1, or MATE2-K within 4 weeks prior to randomization and unwilling and/or unable to avoid these medications throughout the treatment duration NOTE: Participants 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 active viral or bacterial infection within 2 weeks prior to and during the Screening Period
- •Unable to tolerate oral medication or have a condition that would interfere with the absorption of JNT-517
- •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× 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 <11.0 grams per deciliter (g/dL) [<110.0 grams per liter (g/L)]-White blood cell count >ULN-Platelets <150 × 10^9/Liter (L) (<150,000/cubic millimeters [mm^3]).
研究组 & 干预措施
Drug: JNT-517 - 150 mg BID (Tablet)
Experimental
干预措施: JNT-517 Tablet (Drug)
Drug: JNT-517 - 75 mg BID (Tablet)
Experimental
干预措施: JNT-517 Tablet (Drug)
Placebo - BID
Placebo Comparator
One-third (1/3) of participants in the study will be assigned to placebo twice daily (BID) during Treatment Period Part 1. After 6 weeks, these participants will transition to Treatment Period Part 2 and receive JNT-517 at 150 mg BID for 46 weeks.
干预措施: Placebo Tablet: BID (Drug)
结局指标
主要结局
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 group
时间窗: Baseline visit to Week 6
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
时间窗: Baseline to End of Period 1 (Week 6)
次要结局
- Participants achieving plasma Phe levels <360 μmol/L at end of Period 1 in the 150 mg BID and 75 mg BID groups, respectively(Baseline visit to Week 6)
- 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, respectively(Baseline 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 group(Baseline 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, respectively(Baseline 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, respectively(Baseline visit to Week 6)
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))
- Change From Baseline in CANTAB Stop Signal Reaction Time During Period 2(Baseline to End of Period 2 (Week 52))
- 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))
- 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))
研究者
研究点 (26)
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