A Phase I/II Clinical Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of ITU512 in Healthy Participants and Patients With Sickle Cell Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 161
- 试验地点
- 10
- 主要终点
- Part 1A, Part 1B, Part 1C: Incidence of AEs and SAEs
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary food effect of ITU512 as well as the fetal hemoglobin (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512 in healthy participants and patients with sickle cell disease (SCD).
详细描述
This is a global, randomized, Phase I/II study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary food effect of single-agent ITU512 in adult healthy participants, and safety, tolerability, PK, PD, and efficacy of ITU512 in adolescent and adult patients with sickle cell disease (SCD). The study consists of a first-in-human Phase I study (Part 1) in healthy participants, and a Phase II study (Part 2) in patients with SCD.
Part 1 will comprise of Part 1A, Part 1B, and Part 1C. Part 2 will include Part 2A and 2B and may also include an extension part (Part 2C).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part 1 (Healthy participants)
- •Healthy male participants and female participants of non-childbearing potential between 18-55 years of age
- •In good health as determined by the investigator's assessment of medical history, physical examination, vital signs, ECG, and laboratory tests
- •Participants must weigh at least 50 kg at screening and first baseline (admission) and must have a body mass index (BMI) within the range of 18.0-32.0 kg/m2 inclusive.
- •Part 2 (Sickle Cell Disease)
- •- Male and female participants with a diagnosis of sickle cell disease
排除标准
- •Part 1 (Healthy participants)
- •QTcF ≥ 450 msec (as a mean value of triplicates)
- •History of arrhythmias
- •History of significant illness which has not resolved within two (2) weeks prior to initial dosing
- •Women of child-bearing potential (WOCBP)
- •Part 2 (Sickle Cell Disease)
- •Current use of hydroxyurea/hydroxycarbamide (HU/HC)
- •QTcF ≥ 450 msec (as a mean value of triplicates)
- •History of arrhythmias
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Part 1B
Part 1B in healthy participants
干预措施: ITU512 (Drug)
Part 1A
Part 1A in healthy participants
干预措施: ITU512 (Drug)
Part 1B
Part 1B in healthy participants
干预措施: Placebo (Drug)
Part 1C
Part 1C in healthy participants
干预措施: ITU512 (Drug)
Part 2B
Part 2B in patients with sickle cell disease
干预措施: ITU512 (Drug)
Part 2A
Part 2A in patients with sickle cell disease
干预措施: ITU512 (Drug)
Part 2A
Part 2A in patients with sickle cell disease
干预措施: Placebo (Drug)
Part 2B
Part 2B in patients with sickle cell disease
干预措施: Placebo (Drug)
Part 1A
Part 1A in healthy participants
干预措施: Placebo (Drug)
Part 2C
Optional extension in patients with sickle cell disease
干预措施: ITU512 (Drug)
结局指标
主要结局
Part 1A, Part 1B, Part 1C: Incidence of AEs and SAEs
时间窗: Up to approximately 60 days
Number of participants with adverse events (AEs) and serious adverse events (SAEs), including changes in vital signs, electrocardiograms (ECGs) and laboratory values qualifying and reported as AEs.
Part 1A, Part 1B , Part 1C: Dose discontinued due to AE
时间窗: Up to 30 days
Number of participants with dose discontinuation due to AEs
Part 2A, Part 2B: Incidence of AEs and SAEs
时间窗: Up to 5 months
Number of participants with adverse events (AEs) and serious adverse events (SAEs), including changes in vital signs, electrocardiograms (ECGs) and laboratory values qualifying and reported as AEs.
Part 2A, Part 2B: Dose interruptions and reductions
时间窗: Up to 4 months
Number of participants with dose interruptions or reductions of ITU512
Part 2A, Part 2B: Dose intensity
时间窗: Up to 4 months
Dose intensity of ITU512 is computed as the ratio of actual cumulative dose received and actual duration of exposure
Part 2B: Fetal hemoglobin (HbF)%
时间窗: Month 4
Assessment of fetal hemoglobin expression by measuring fetal hemoglobin (HbF)% by high-performance liquid chromatography (HPLC) assay
次要结局
- Part 1A, Part 1B: Area under the plasma concentration-time curve (AUC) of ITU512(From pre-dose up to 144 hours post-dose on Day 1 (Part 1A) and from pre-dose up to 24 hours post-dose on Day 1 and Day 10 (Part 1B))
- Part 1A, Part 1B: Maximum plasma concentration (Cmax) of ITU512(From pre-dose up to 144 hours post-dose on Day 1 (Part 1A) and from pre-dose up to 24 hours post-dose on Day 1 and Day 10 (Part 1B))
- Part 1A, Part 1B: Time to maximum plasma concentration (Tmax) of ITU512(From pre-dose up to 144 hours post-dose on Day 1 (Part 1A) and from pre-dose up to 24 hours post-dose on Day 1 and Day 10 (Part 1B))
- Part 1A, Part 1B: Renal clearance (CLr)(From pre-dose up to 48 hours post-dose on Day 1 (Part 1A) and from pre-dose up to 24 hours post-dose on Day 1 and Day 10 (Part 1B))
- Part 1C: Area under the plasma concentration-time curve from time 0 up to the time of the last quantifiable concentration (AUClast) of ITU512(From pre-dose up to 144 hours post-dose)
- Part 1C: Area under the plasma concentration-time curve from time 0 up to infinity (AUCinf) of ITU512(From pre-dose up to 144 hours post-dose)
- Part 1C: Maximum plasma concentration (Cmax) of ITU512(From pre-dose up to 144 hours post-dose)
- Part 1C: Time to maximum plasma concentration (Tmax) of ITU512(From pre-dose up to 144 hours post-dose)
- Part 2A, Part 2B: Plasma concentrations of ITU512(From pre-dose up to 4, 6 or 8 hours post-dose on Day 1 at Month 1 and Month 2)
- Part 2A, Part 2B: Urine concentrations of ITU512(From pre-dose up to 4 or 8 hours post-dose on Day 1 at Month 1)
- Part 2A: Fetal hemoglobin (HbF)%(Up to 4 months)
- Part 2A, Part 2B: Change from baseline in total hemoglobin (Hb)(Baseline, up to 4 months)
- Part 1A, Part 1B, Part 2A, Part 2B: Change from baseline in Fridericia- corrected Holter QT interval (QTcF)(Up to 4 months)