A Phase 1, Blinded, Randomized, Placebo-controlled, First-in-human Study of Orally Administered JNJ-64457744 to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Single and Multiple Ascending Doses
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Part 1, 2 and 3: Number of Participants With Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of the study is to evaluate the safety and tolerability of: single ascending dose (SAD) and multiple ascending dose (MAD) administration of JNJ-64457744, administered to healthy adult participants (Part 1 and Part 3), including a cohort of Asian participants (Part 1); and after single dose administration of JNJ-64457744 to chronic hepatitis B (CHB) participants who are virologically suppressed on nucleos(t)ide analog (NA) treatment (tenofovir disoproxil fumarate [TDF], tenofovir alafenamide [TAF], or entecavir [ETV]) (Part 2).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Normal left ventricular heart function as defined as left ventricular ejection fraction (LVEF) greater than or equal to (>=) 5 percent (%), as assessed by 2 dimension electrocardiogram (2DECHO) at screening
- •All women must have a negative urine pregnancy test at screening and Day -1 (of each intervention period, if applicable)
- •A woman must not be of childbearing potential
- •Part 1 and 3: Must have an estimated creatinine clearance greater than (>) 80 milliliter (mL) per minute at screening, calculated by the modification of diet in renal disease (MDRD) formula
- •Part 2: Must have chronic HBV infection. HBV infection must be documented by serum HBsAg positivity at screening
- •Must be fully vaccinated against coronavirus disease 2019 (COVID-19) at least 2 weeks prior to screening calculated by the modification of diet in renal disease (MDRD) formula
- •Participants in Cohorts A-I and K in Part 1 must not have maternal and paternal parents and/or grandparents of Asian ethnicity (that is, China, Japan, Korea as confirmed by interview) Participants in Cohort J must have maternal and paternal parents and grandparents of Asian ethnicity (that is, China, Japan, Korea as confirmed by interview)
排除标准
- •History of cardiac arrhythmias (example, extrasystole, tachycardia at rest), history of risk factors for Torsades de Pointes syndrome (example, hypokalemia, family history of long QT syndrome) or history or other clinical evidence of significant or unstable cardiac disease (example, angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease, and/or clinically significant electrocardiogram ([ECG] abnormalities), moderate to severe valvular disease or uncontrolled hypertension at screening. Any evidence of second and third degree heart block or right bundle branch block is also exclusionary
- •Participants with abnormal sinus rhythm (heart rate less than [<] 45 or > 100 beats per minute [bpm]), QT corrected for heart rate according to Fridericia's formula (QTcF) > 450 milliseconds (ms) for male participants and > 470 ms for female participants, QRS >= 120 ms, PR interval >220 ms, abnormal conduction, or any other clinically significant abnormalities on a 12-lead ECG at screening
- •Family history of inherited mitochondrial disorders such as inherited mitochondrial myopathy, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome
- •Known allergies, hypersensitivity, or intolerance to JNJ-64457744 or its excipients
- •History of clinically significant drug allergy such as, but not limited to, sulfonamides and penicillins, or drug allergy witnessed in previous studies with experimental drugs
研究组 & 干预措施
Part 1: JNJ-64457744 or Placebo (Single Ascending Dose [SAD] Cohorts A-F)
Non-Asian healthy participants will receive a SAD of either JNJ-64457744 or matching placebo as an oral formulation under fasted conditions on Day 1. Cohort F will be optional.
干预措施: JNJ-64457744 (Drug)
Part 1: JNJ-64457744 or Placebo (Single Ascending Dose [SAD] Cohorts A-F)
Non-Asian healthy participants will receive a SAD of either JNJ-64457744 or matching placebo as an oral formulation under fasted conditions on Day 1. Cohort F will be optional.
干预措施: Placebo (Drug)
Part 1: JNJ-64457744 (Cohorts G-H)
Non-Asian healthy participants will receive 3 single doses of JNJ-64457744 as an oral formulation in 3 intervention periods (to assess inter-subject PK-PD) matching the doses evaluated in Cohorts A, C and E for Cohort G and Cohorts B, D and F for Cohort H, under fasted conditions on Day 1. Cohort H will be optional for Intervention period 3.
干预措施: JNJ-64457744 (Drug)
Part 1: JNJ-64457744 or Placebo (Cohort I)
Non-Asian healthy participants who previously received study intervention under fasted conditions will receive either JNJ-64457744 or matching placebo as an oral formulation (depending upon what was administered previously in Cohorts A to F) under fed conditions on Day 1.
干预措施: JNJ-64457744 (Drug)
Part 1: JNJ-64457744 or Placebo (Cohort I)
Non-Asian healthy participants who previously received study intervention under fasted conditions will receive either JNJ-64457744 or matching placebo as an oral formulation (depending upon what was administered previously in Cohorts A to F) under fed conditions on Day 1.
干预措施: Placebo (Drug)
Part 1: JNJ-64457744 or Placebo (Cohort J)
Asian healthy participants will receive a single dose at one single dose level of either JNJ-64457744 or matching placebo, as an oral formulation, under fasted conditions on Day 1.
干预措施: JNJ-64457744 (Drug)
Part 1: JNJ-64457744 or Placebo (Cohort J)
Asian healthy participants will receive a single dose at one single dose level of either JNJ-64457744 or matching placebo, as an oral formulation, under fasted conditions on Day 1.
干预措施: Placebo (Drug)
Part 1: JNJ-64457744 (Cohort K)
Optional Cohort K: Non-Asian healthy participants will receive an oral formulation of JNJ-64457744 in the first intervention period and will cross over to receive the other formulation during the second intervention period, under fasted conditions on Day 1.
干预措施: JNJ-64457744 (Drug)
Part 2 JNJ-64457744 or Placebo
Chronic hepatitis B participants who are virologically suppressed on nucleos(t)ide analog (NA) treatment (tenofovir disoproxil fumarate [TDF], tenofovir alafenamide [TAF] and entecavir [ETV]) will receive a single dose at one single dose level of either JNJ-64457744 or matching placebo as an oral formulation, under fasted condition on Day 1.
干预措施: JNJ-64457744 (Drug)
Part 2 JNJ-64457744 or Placebo
Chronic hepatitis B participants who are virologically suppressed on nucleos(t)ide analog (NA) treatment (tenofovir disoproxil fumarate [TDF], tenofovir alafenamide [TAF] and entecavir [ETV]) will receive a single dose at one single dose level of either JNJ-64457744 or matching placebo as an oral formulation, under fasted condition on Day 1.
干预措施: Placebo (Drug)
Part 2 JNJ-64457744 or Placebo
Chronic hepatitis B participants who are virologically suppressed on nucleos(t)ide analog (NA) treatment (tenofovir disoproxil fumarate [TDF], tenofovir alafenamide [TAF] and entecavir [ETV]) will receive a single dose at one single dose level of either JNJ-64457744 or matching placebo as an oral formulation, under fasted condition on Day 1.
干预措施: Tenofovir Disoproxil Fumarate (TDF) (Drug)
Part 2 JNJ-64457744 or Placebo
Chronic hepatitis B participants who are virologically suppressed on nucleos(t)ide analog (NA) treatment (tenofovir disoproxil fumarate [TDF], tenofovir alafenamide [TAF] and entecavir [ETV]) will receive a single dose at one single dose level of either JNJ-64457744 or matching placebo as an oral formulation, under fasted condition on Day 1.
干预措施: Tenofovir Alafenamide (TAF) (Drug)
Part 2 JNJ-64457744 or Placebo
Chronic hepatitis B participants who are virologically suppressed on nucleos(t)ide analog (NA) treatment (tenofovir disoproxil fumarate [TDF], tenofovir alafenamide [TAF] and entecavir [ETV]) will receive a single dose at one single dose level of either JNJ-64457744 or matching placebo as an oral formulation, under fasted condition on Day 1.
干预措施: Entecavir (ETV) (Drug)
Part 3: JNJ-64457744 or Placebo (Multiple Ascending Doses [MADs])
Participants will receive MADs of either JNJ-64457744 or matching placebo once weekly under fasted conditions as an oral formulation.
干预措施: JNJ-64457744 (Drug)
Part 3: JNJ-64457744 or Placebo (Multiple Ascending Doses [MADs])
Participants will receive MADs of either JNJ-64457744 or matching placebo once weekly under fasted conditions as an oral formulation.
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1, 2 and 3: Number of Participants With Serious Adverse Events (SAEs)
时间窗: Up to Week 8
SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; suspected transmission of any infectious agent via medicinal product; or any important medical events.
Part 1, 2 and 3: Number of Participants With Clinical Laboratory Abnormalities by Severity
时间窗: Up to 8 weeks
Number of participants with clinical laboratory abnormalities (including hematology, biochemistry, coagulation, urinalysis) will be reported. Severity will be graded according to the Division of AIDS (DAIDS) grading table where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Potentially Life-threatening.
Part 1, 2 and 3: Number of Participants With Clinical Laboratory Abnormalities
时间窗: Up to 8 weeks
Number of participants with clinical laboratory abnormalities (including hematology, biochemistry, coagulation, urinalysis) will be reported.
Part 1, 2 and 3: Number of Participants With Electrocardiograms (ECGs), Echocardiography, Vital Signs and Physical Examination Abnormalities
时间窗: Up to Week 8
Number of participants with abnormalities in ECGs, echocardiography, vital signs and physical examination will be reported.
Part 1, 2 and 3: Number of Participants With SAEs by Severity
时间窗: Up to Week 8
SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; suspected transmission of any infectious agent via medicinal product; or any important medical events. Severity will be graded according to the Division of Division of Acquired Immunodeficiency Syndrome (DAIDS) grading table where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Potentially Life-threatening.
Part 1, 2 and 3: Plasma concentration of JNJ-64457744
时间窗: Up to Week 8
Plasma concentration of JNJ-64457744 will be reported.
Part 1, 2 and 3: Number of Participants With Electrocardiograms (ECGs), Echocardiography, Vital Signs and Physical Examination Abnormalities by Severity
时间窗: Up to 8 weeks
Number of participants with abnormalities in ECGs, echocardiography, vital signs and physical examination will be reported. Severity will be graded according to the Division of AIDS (DAIDS) grading table where Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Potentially Life-threatening.
次要结局
- Part 1: Plasma Concentration of JNJ-64457744 Under Fasted Condition in Healthy Adult Asian Participants(Up to 5 weeks)
- Part 1: Plasma Concentration of JNJ-64457744: Within-Participant Analysis(Up to 5 weeks)
- Part 1: Plasma Concentration of JNJ-64457744 Under Fed and Fasted Condition(Up to 5 weeks)
- Part 1: Plasma Concentration of JNJ-64457744 Formulation Under Fasted Conditions(Up to 5 weeks)