A Randomized, Double-Blind, Placebo-Controlled, Single (SAD) and Multiple Ascending-Dose (MAD) Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AKB-9090 Administered Intravenously to Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Number of participants who will report serious Treatment emergent adverse events (TEAEs) and TEAEs
研究概览
简要总结
This is a first-in-human (FIH study designed to evaluate safety, tolerability, pharmacokinetic, and pharmacodynamic effects of AKB-9090 in healthy adult participants. The study consists of two stages: Stage 1, a single ascending dose (SAD) phase with four dose cohorts, and Stage 2, a multiple ascending dose (MAD) phase with one dose cohort. Approximately 32 participants in SAD and 12 in MAD are planned to be enrolled.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult participants with no clinically significant findings, as judged by the investigator, based on physical examination, 12-lead ECG, alcohol breath test, and clinical laboratory tests (including serum chemistry, hematology, coagulation, urine drug screen, and urinalysis).
- •Body mass index (BMI) greater than 18.5 and less than 32.0 kg/m^2 at screening.
- •In the Investigator's opinion, willing and able to provide written informed consent and comply with the all protocol requirements, including required confinement, outpatient visits, and protocol-specified restrictions (including refraining from major lifestyle changes) from signature of the informed consent form (ICF) through the last study visit.
排除标准
- •Clinically significant metabolic, hepatic, renal, hematologic, pulmonary, cardiovascular, gastrointestinal, musculoskeletal, dermatologic, urogenital, ophthalmologic, ear/nose/throat, psychiatric, or neurologic disorder.
- •History of active or recurrent malignancy within 2 years before screening or during the screening period, or currently receiving treatment or suppressive therapy for cancer, except for:
- •Treated basal cell carcinoma of the skin
- •Curatively resected squamous cell carcinoma of the skin
- •Treated colonic or cervical carcinoma in situ
- •Abnormal ECG findings at screening, including:
- •Severe bradycardia (heart rate <40 beats per minute) on any measurement
- •Mean QT Interval Using Fridericia's Formula (QTcF) >450 msec for males or >470 msec for females
- •Elevated laboratory values (>1.25 × upper limit of normal [ULN]) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), or creatinine at the screening visit or at check-in.
- •Evidence of acute or chronic hepatitis B (positive hepatitis B surface antigen) or hepatitis C infection (positive hepatitis C antibody and positive hepatitis C ribonucleic acid [RNA] test).
- •Use of nicotine-containing products (including cigarettes, cigars, tobacco, gum, patches, vaping, and e-cigarettes), caffeine-containing foods or beverages, and alcohol-containing foods or beverages during study.
研究组 & 干预措施
Placebo
Single IV dose of matching Placebo.
干预措施: Placebo (Other)
AKB-9090
Participants will receive a single intravenous (IV) dose of AKB-9090 at 4 escalating dose levels in the SAD stage and at 1 dose level in the MAD stage.
干预措施: AKB-9090 (Drug)
结局指标
主要结局
Number of participants who will report serious Treatment emergent adverse events (TEAEs) and TEAEs
时间窗: From First Dose to Day 7
Number of Participants with Clinically Significant Changes in Physical Examinations
时间窗: From First Dose to Day 7
Number of Participants with Clinically Significant Changes in Vital Signs
时间窗: From First Dose to Day 7
Number of Participants with Clinically Significant Changes in 12-lead Electrocardiogram (ECG)
时间窗: From First Dose to Day 7
Number of Participants with Clinically Significant Changes in Chemistry parameters
时间窗: From First Dose to Day 7
Number of Participants with Clinically Significant Changes in Hematology Parameters
时间窗: from first dose to Day 7
Number of Participants with Clinically Significant Changes in Lipid Parameters
时间窗: From First Dose to Day 7
Number of Participants with Clinically Significant Changes in Coagulation Parameters
时间窗: From First Dose to Day 7
Number of Participants with Clinically Significant Changes in Urinalysis Parameters
时间窗: From First Dose to Day 7
次要结局
- Stage 1 SAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - Reticulocyte Count(Baseline (Day 1) and At Days 2, 8, and 13)
- Stage 1 SAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - Red Blood Cell Count (RBC)(Baseline (Day 1) and At Days 2, 8, and 13)
- Stage 2 MAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - RBC(Baseline (Day 1) and At Days 4, 8, 14, and 21)
- Stage 2 MAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - Reticulocyte Count(Baseline (Day 1) and At Days 4, 8, 14, and 21)
- Stage 1 SAD Cohorts: Maximum observed plasma concentration (Cmax) of AKB-9090(At Day 1)
- Stage 1 SAD Cohorts: Time of maximum plasma concentration (Tmax) of AKB-9090(At Day 1)
- Stage 1 SAD Cohorts: Area under concentration time curve (AUC) from time 0 to the last observation (AUClast) of AKB-9090(At Day 1)
- Stage 1 SAD Cohorts: Apparent body clearance (CL) of AKB-9090(At Day 1)
- Stage 1 SAD Cohorts: AUC from time 0 to infinity (AUCinf) of AKB-9090(At Day 1)
- Stage 1 SAD Cohorts: Terminal half-life (T1/2) of AKB-9090(At Day 1)
- Stage 2 MAD Cohorts: Cmax of AKB-9090(At Day 1 and Day 7)
- Stage 2 MAD Cohorts: Tmax of AKB-9090(At Day 1 and Day 7)
- Stage 2 MAD Cohorts: AUC to 24 hours post-dose (AUC24) of AKB-9090(At Day 1)
- Stage 2 MAD Cohorts: CL of AKB-9090(At Day 1 and Day 7)
- Stage 2 MAD Cohorts: T1/2 of AKB-9090(At Day 1 and Day 7)
- Stage 2 MAD Cohorts: AUC at Steady state (AUCss) of AKB-9090(At Day 7)
- Stage 1 SAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - Erythropoietin (EPO)(Baseline (Day 1) and at 6, 12, 18, and 24 hours post-dose)
- Stage 1 SAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - Red Blood Cell Count (RBC)(Baseline (Day 1) and At Day 2)
- Stage 1 SAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - Reticulocyte Count(Baseline (Day 1) and At Day 2)
- Stage 2 MAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - EPO(Baseline (Day 1 and Day 7) and at 6, 12, 18, and 24 hours post-dose)
- Stage 2 MAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - RBC(Baseline (Day 1) and At Days 4 and 8)
- Stage 2 MAD Cohorts: Change from Baseline in Pharmacodynamic Biomarker - Reticulocyte Count(Baseline (Day 1) and At Days 4 and 8)