A Phase 1/2, First-In-Human, Multiple Part, Single Ascending and Multiple Dose Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 163
- 试验地点
- 30
- 主要终点
- Number of participants with treatment-emergent adverse events
研究概览
简要总结
The goal of Parts A and B of this Phase 1/2, first-in-human, randomized study is to assess the safety, tolerability, and pharmacokinetics (PK) of single (SAD) and multiple (MAD) ascending doses of oral JNT-517 in healthy participants. In Part C, the goal is to evaluate the differences in bioavailability between a tablet and suspension formulation of JNT-517 and the food effect in healthy volunteers. All participants in Part C will receive JNT-517. The goal of Part D is to assess the safety, tolerability, PK, and effect on urinary Phe and other amino acids of JNT-517 in participants with phenylketonuria (PKU). Participants in Part D will receive either JNT-517 or placebo and will be blinded to their treatment assignment.
The study consists of 6 parts:
- Part A: SAD in healthy participants -randomized, double-blind, placebo-controlled
- Part B: MAD in healthy participants (14 days)-randomized, double-blind, placebo-controlled
- Part C: Relative bioavailability of 2 formulations and food effect in healthy participants-randomized, open-label
- Part D: Phase 2 in participants with PKU (4 weeks)-randomized, double-blind, placebo-controlled
- Part E: Phase 2 in participants with PKU (4 weeks) open label
- Part F: SAD Phase 1 in healthy participants, randomized, double-blind, placebo-controlled
In each part, participants will complete a Screening Period, a Treatment Period, and a Follow-up Period for safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Parts A, B, D, and F are blinded. Parts C and E are open-label.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Parts A, B, C, and F:
- •Males and females 18 to 55 years of age.
- •Medically healthy with no clinically significant medical history.
- •Body mass index (BMI) of 18-40 kg/m2 and total body weight >50 kg (110 lbs).
- •Non-smoker for at least 2 weeks prior to dosing and willing to abstain during the study.
- •Part D and E:
- •Males and females 18 to 65 years of age, inclusive.
- •Diagnosis of PKU with a confirmed genotype.
- •At least 2 plasma Phe levels >600 μM over the past 12 months.
- •BMI of 18-40 kg/m
- •Females of childbearing potential must agree to use 2 highly effective contraceptive methods.
- •Capable of giving signed informed consent and able to comply with study procedures.
排除标准
- •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 malignancy in the last 5 years, excluding non-melanoma skin cancer.
- •Any history of liver disease.
- •Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.
- •Participation in another investigational drug trial within 30 days or, if known, 5 half-lives of the investigational drug (whichever is longer).
- •History of drug/alcohol abuse in the last year.
- •Current, recent, or suspected infection within 4 weeks of Screening of SARS-CoV-2/COVID-
- •Received a vaccine for SARS-CoV-2/COVID-19 within 14 days of Screening.
- •Unable to tolerate oral medication.
- •Allergy to JNT-517 or any component of the investigational product.
- •Received >50 mL of blood or plasma within 30 days of Screening or >500 mL of blood or plasma within 60 days of Screening.
研究组 & 干预措施
JNT-517 SAD (Part A and Part F)
Single dose of JNT-517 or placebo in fasted state.
干预措施: JNT-517 Suspension (Drug)
JNT-517 SAD (Part A and Part F)
Single dose of JNT-517 or placebo in fasted state.
干预措施: Placebo Suspension (Drug)
JNT-517 MAD (Part B)
JNT-517 or placebo once or twice daily for 14 days, with first daily dose given after an overnight fast.
干预措施: JNT-517 Suspension (Drug)
JNT-517 MAD (Part B)
JNT-517 or placebo once or twice daily for 14 days, with first daily dose given after an overnight fast.
干预措施: Placebo Suspension (Drug)
JNT-517 Tablet Fasted Then Tablet Fed Then Suspension (Part C)
Single dose of JNT-517 tablet in a fasted state, JNT-517 tablet in a fed state, and JNT-517 suspension in a sequential, open-label manner. Each treatment is separated by a minimum of 5 half-lives.
干预措施: JNT-517 Tablet (Drug)
JNT-517 Suspension Then Tablet Fasted Then Tablet Fed (Part C)
Single dose of JNT-517 suspension, JNT-517 tablet in a fasted state, and JNT-517 tablet in a fed state in a sequential, open-label manner. Each treatment is separated by a minimum of 5 half-lives.
干预措施: JNT-517 Suspension (Drug)
JNT-517 Suspension Then Tablet Fasted Then Tablet Fed (Part C)
Single dose of JNT-517 suspension, JNT-517 tablet in a fasted state, and JNT-517 tablet in a fed state in a sequential, open-label manner. Each treatment is separated by a minimum of 5 half-lives.
干预措施: JNT-517 Tablet (Drug)
JNT-517 Tablet Fasted Then Tablet Fed Then Suspension (Part C)
Single dose of JNT-517 tablet in a fasted state, JNT-517 tablet in a fed state, and JNT-517 suspension in a sequential, open-label manner. Each treatment is separated by a minimum of 5 half-lives.
干预措施: JNT-517 Suspension (Drug)
JNT-517 Tablet Fed Then Suspension Then Tablet Fasted (Part C)
Single dose of JNT-517 tablet in a fed state, JNT-517 suspension, and JNT-517 tablet in a fasted state in a sequential, open-label manner. Each treatment is separated by a minimum of 5 half-lives.
干预措施: JNT-517 Suspension (Drug)
JNT-517 Tablet Fed Then Suspension Then Tablet Fasted (Part C)
Single dose of JNT-517 tablet in a fed state, JNT-517 suspension, and JNT-517 tablet in a fasted state in a sequential, open-label manner. Each treatment is separated by a minimum of 5 half-lives.
干预措施: JNT-517 Tablet (Drug)
JNT-517 PKU (Part D and E)
JNT-517 or placebo daily for 4 weeks. Dose is based on data from Parts A, B, and C.
干预措施: JNT-517 Tablet (Drug)
JNT-517 PKU (Part D and E)
JNT-517 or placebo daily for 4 weeks. Dose is based on data from Parts A, B, and C.
干预措施: Placebo Tablet (Drug)
结局指标
主要结局
Number of participants with treatment-emergent adverse events
时间窗: Parts A/C/F: Screening to Day 8; Part B: Screening to Day 21; Part D/E: Screening to Day 35
Reported based on results of 12-lead ECGs, vital signs, clinical laboratory tests, and other medical assessments.
次要结局
- Plasma area under the concentration-time curve (AUC) of JNT-517(Parts A/C/F: pre-dose to 72 hrs post-dose on Day 1; Part B: pre-dose to 24 hrs post-dose on Days 1, 14 and pre-dose on Days 3, 13; Part D/E: pre-dose to 4 hrs post-dose on Days 1, 14, 28)
- Maximum observed plasma concentration (Cmax) of JNT-517(Parts A/C/F: pre-dose to 72 hrs post-dose on Day 1; Part B: pre-dose to 24 hrs post-dose on Days 1, 14 and pre-dose on Days 3, 13; Part D/E: pre-dose to 4 hrs post-dose on Days 1, 14, 28)
- Time to maximum plasma concentration (Tmax) of JNT-517(Parts A/C/F: pre-dose to 72 hrs post-dose on Day 1; Part B: pre-dose to 24 hrs post-dose on Days 1, 14 and pre-dose on Days 3, 13; Part D/E: pre-dose to 4 hrs post-dose on Days 1, 14, 28)
- Plasma terminal half-life (t1/2) of JNT-517(Parts A/C/F: pre-dose to 72 hrs post-dose on Day 1; Part B: pre-dose to 24 hrs post-dose on Days 1, 14 and pre-dose on Days 3, 13; Part D/E: pre-dose to 4 hrs post-dose on Days 1, 14, 28)
- Comparison of Tmax of JNT-517 in fed and fasted states(Pre-dose to 72 hrs post-dose on Day 1)
- Comparison of Cmax of JNT-517 in fed and fasted states(Pre-dose to 72 hrs post-dose on Day 1)
- Comparison of AUC of JNT-517 in fed and fasted states(Pre-dose to 72 hrs post-dose on Day 1)
- Changes in urinary amino acid levels(Screening and Days 1, 7, 14, 21, 28)