A Phase 1a/1b, Blinded, Placebo-Controlled Study of the Safety, Tolerability and Pharmacokinetics of Single- and Multiple-Ascending Doses of ABI-5366 in Healthy Subjects and in Subjects Who Are Seropositive for Herpes Simplex Virus Type 2 With Recurrent Genital Herpes
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 115
- 试验地点
- 15
- 主要终点
- Apparent Terminal Elimination Half Life (t 1/2) of ABI-5366
研究概览
简要总结
This study is designed to assess safety, tolerability, and pharmacokinetics (PK) of single ascending dose (SAD) of ABI-5366 in Part A in healthy participants and multiple-ascending doses (MAD) of ABI-5366 in Part B in participants seropositive for Herpes Simplex Virus Type 2 (HSV-2) with recurrent genital herpes. Effect of food will also be evaluated in Part A.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject has a body mass index (BMI) between ≥ 18.0 and < 32.0 kg/m2
- •In good health (as determined by the Investigator) based on medical history, physical examination, ECG, and clinical laboratory results.
- •Female subjects must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day -1 or Day 1 (predose)
- •Agreement to comply with protocol-specified contraceptive requirements
- •Part B: Inclusion Criteria:
- •Subject has a body mass index (BMI) between ≥ 18.0 and < 32.0 kg/m2
- •Other than HSV infection, is in good health (as determined by the Investigator) based on medical history, physical examination, ECG, and clinical laboratory results.
- •Female subjects must be non-pregnant and have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Day 1 (predose)
- •Agreement to comply with protocol-specified contraceptive requirements
- •Part A and B:
排除标准
- •Current infection of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), acute hepatitis A virus (HAV), or acute hepatitis E virus (HEV).
- •History of any illness that, in the opinion of the Investigator, might confound the results of the study, pose an additional risk in administering study drug to the subject, or a condition known to interfere with the absorption/distribution/elimination of drugs.
- •History of any significant drug-related allergic reactions such as anaphylaxis, Stevens-Johnson syndrome, urticaria, or multiple drug allergies
- •History of persistent alcohol abuse or illicit drug abuse within 3 years prior to Screening
- •Has participated in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 half-lives before Screening, whichever is longer.
研究组 & 干预措施
Part A: SAD Cohorts 1-5, ABI-5366
Single dose of ABI-5366 (tablet) in Part A for Cohorts 1-5
干预措施: ABI-5366 Placebo (Drug)
Part A: SAD Cohorts 1-5, Placebo
Single dose of matching placebo (tablet) in Part A for Cohorts 1-5
干预措施: ABI-5366 (Drug)
Part A: SAD Cohorts 1-5, ABI-5366
Single dose of ABI-5366 (tablet) in Part A for Cohorts 1-5
干预措施: ABI-5366 (Drug)
Part A: SAD Cohorts 1-5, Placebo
Single dose of matching placebo (tablet) in Part A for Cohorts 1-5
干预措施: ABI-5366 Placebo (Drug)
Part A: SAD Fed Cohort 6, ABI-5366
Single dose of ABI-5366 (tablet) in Part A for Cohort 6, food effect
干预措施: ABI-5366 (Drug)
Part B: MAD Cohorts 1-4 ABI-5366
Weekly or monthly dose of ABI-5366 (tablet) in Part B for Cohorts 1-4. May have a loading dose.
干预措施: ABI-5366 (Drug)
Part B: MAD Cohorts 1-4 ABI-5366
Weekly or monthly dose of ABI-5366 (tablet) in Part B for Cohorts 1-4. May have a loading dose.
干预措施: ABI-5366 Placebo (Drug)
Part B: MAD Cohorts 1-4 Placebo
Weekly or monthly dose of matching placebo (tablet) in Part B for Cohorts 1-4. May have a loading dose.
干预措施: ABI-5366 (Drug)
Part B: MAD Cohorts 1-4 Placebo
Weekly or monthly dose of matching placebo (tablet) in Part B for Cohorts 1-4. May have a loading dose.
干预措施: ABI-5366 Placebo (Drug)
结局指标
主要结局
Apparent Terminal Elimination Half Life (t 1/2) of ABI-5366
时间窗: SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Area Under the Plasma Concentration Time Curve (AUC) of ABI-5366
时间窗: SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Maximum Observed Plasma Concentration (Cmax) of ABI-5366
时间窗: SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Apparent Volume of Distribution (Vz/F) of ABI-5366
时间窗: SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Time to Cmax (Tmax) of ABI-5366
时间窗: SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Apparent Systemic Clearance (CL/F) of ABI-5366
时间窗: SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Dose normalized AUCs and Cmax of ABI-5366
时间窗: SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing. MAD Cohorts: before and at pre-specified time points up to 8 hours after dosing.
Proportion of subjects with adverse events (AEs), premature treatment discontinuation due to AEs, and abnormal laboratory results
时间窗: Up to 98 days after last dose
次要结局
- SAD Cohorts: Comparison of plasma AUC and Cmax between fasted and fed treatments(SAD Cohorts: before and at pre-specified time points up to 168 hours after dosing.)
- MAD Cohorts: Difference in lesion rate during the swabbing period across treatments(MAD Cohorts: At pre-specified time points from Days 8 to 36.)
- MAD Cohorts: If applicable, comparison of plasma PK profiles and parameters with and without loading doses(MAD Cohorts: At pre-specified time points from Days 8 to 36.)
- MAD Cohorts: Difference in viral shedding rate (number of anogenital swabs positive for HSV-2 DNA/total number of swabs) across treatments(MAD Cohorts: At pre-specified time points from Days 8 to 36.)
- MAD Cohorts: Difference in mean and median HSV-2 DNA copies/mL for swab samples positive for HSV-2 DNA across treatments(MAD Cohorts: At pre-specified time points from Days 8 to 36.)
- MAD Cohorts: Difference in the proportion of swab samples with HSV-2 DNA >4 log10 copies/mL across treatments (number of swabbing samples with HSV-2 DNA >4 log10 copies/mL / total number of swabs obtained)(MAD Cohorts: At pre-specified time points from Days 8 to 36.)
- MAD Cohorts: Difference in number of shedding episodes during the swabbing period across treatments(MAD Cohorts: At pre-specified time points from Days 8 to 36.)
- MAD Cohorts: Difference in duration of shedding episodes during the swabbing period across treatments(MAD Cohorts: At pre-specified time points from Days 8 to 36.)
- MAD Cohorts: Difference in subclinical shedding rate (number of swabs positive for HSV-2 DNA in the absence of lesions/total number of swabs in the absence of lesions) across treatments(MAD Cohorts: At pre-specified time points from Days 8 to 36.)
- MAD Cohorts: Difference in lesion duration during the swabbing period across treatments(MAD Cohorts: At pre-specified time points from Days 8 to 36.)
- MAD Cohorts: Difference in recurrence rate (number of reappearances of lesions during the swabbing period/total days assessed) across treatments(MAD Cohorts: At pre-specified time points from Days 8 to 36.)