An Open-Label, Dose Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Subcutaneous Doses of CBP-4888 in Hospitalized Participants With Preterm Preeclampsia Receiving Standard of Care, Expectant Management
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 3
- 主要终点
- Incidence of treatment emergent events and adverse events of special interest when CBP-4888 is administered to pregnant participants
研究概览
简要总结
This study is a dose finding study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of subcutaneous CBP-4888 in hospitalized participants with Preterm Preeclampsia receiving Standard of Care, Expectant Management. Eligible participants are between 26 +0/7 and 35 +6/7 weeks gestational age and clinically appropriate for inpatient expectant management. Eligible participants will receive standard of care expectant management for their pregnancy with the only study interventions being one subcutaneous dose of CBP-4888.
Participants will:
- receive a single subcutaneous injection dose of CBP-4888 and will be followed through delivery and for 42 days (+14 days) after delivery. Participants will be followed through 6 weeks post delivery.
- Infants will be evaluated immediately postpartum and then followed through 24 months of age with standard infant and pediatric assessments with phone calls made to parents.
详细描述
An Open-Label, Dose Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous CBP-4888 in Hospitalized Participants with Preterm Preeclampsia Receiving Standard of Care, Expectant Management. The study will follow a single ascending dose design, with up to 60 participants enrolled across 6 dose level groups. For each of the planned six dose levels, all 4 participants will receive a single SC injection dose of IP (CBP-4888) + standard of care (SOC)/Expectant Management + additional safety surveillance for the mother and neonate through delivery and for 42 days (+14 days) after delivery. Infants will be followed for up to 24 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Hospitalized with a hypertensive disorder of pregnancy (preeclampsia) defined by elevated blood pressure after 20 weeks gestation with proteinuria or, in the absence of proteinuria, with evidence of organ dysfunction (e.g., thrombocytopenia, renal insufficiency, or impaired liver function), and expected to remain hospitalized through delivery
- •The subject has given written consent to participate in the study.
- •Pregnant participants aged 18 to 45 years of age
- •Gestational age at Day 1 between 26 weeks 0/7 days and 35 weeks 6/7 days
- •Deemed clinically stable and suitable for expectant management for at least 72 hours post CBP-4888 administration
- •The woman carries a singleton pregnancy
- •Anticipate that hospitalization will continue through delivery
排除标准
- •Placenta previa, abruption, accreta, or persistent unexplained vaginal bleeding.
- •Fetal growth restriction (<3rd percentile, or <10th percentile with abnormal Doppler) or known major chromosomal/genetic abnormalities.
- •Maternal conditions requiring immediate delivery (e.g., severe hypertension, eclampsia, non-reassuring fetal status, pulmonary edema).
- •Known active maternal infections considered to potentially affect placental function.
- •Significant maternal medical conditions (e.g., HELLP syndrome, advanced kidney disease, severe cardiac disease, uncontrolled neurological disorder, lupus with nephritis/cerebritis).
- •Use of another investigational drug within 30 days prior to study entry.
- •Any other condition that, in the investigator's judgment, poses risk to mother or fetus.
研究组 & 干预措施
CBP-4888
On Day 1, participants will receive a subcutaneous dose of CBP-4888.
干预措施: CBP-4888 (Drug)
结局指标
主要结局
Incidence of treatment emergent events and adverse events of special interest when CBP-4888 is administered to pregnant participants
时间窗: 6 weeks postpartum
Incidence of treatment-emergent adverse events (TEAEs) in pregnant participants receiving subcutaneous CBP-4888 through delivery (up to 6 weeks postpartum).
Determine recommended phase 2 dose
时间窗: From pre-dose on Day 1 through the last measurable concentration at approximately 72 hours postpartum in serum
To characterize the pharmacodynamic effect of CBP-4888 on maternal plasma sFlt1 levels
次要结局
- Neurodevelopmental Outcomes Assessed by the Ages and Stages Questionnaire (ASQ-3) to investigate long term safety of children of pregnant participants who were administered CBP-4888(From birth through 24 months of age)
- Peak Plasma Concentration (Cmax) of siRNA-2283 siRNA-2519(From pre-dose on Day 1 through the last measurable concentration at approximately 120 hours post-dose)
- Incidence of Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) in Infants Exposed In Utero to CBP-4888(From birth through 180 days of age)
- Time to Peak Concentration (Tmax) of siRNA-2283 siRNA-2519(From pre-dose on Day 1 through the last measurable concentration at approximately 120 hours post-dose)
- Area Under the Concentration (AUC)-Time Curve to Last Measurable Concentration of siRNA-2283 and siRNA-2519(From pre-dose on Day 1 through the last measurable concentration at approximately 120 hours post-dose)