A Single-Blind Dose-Ranging Pharmacodynamic Study of Auxora for the Treatment of Patients With Critical COVID-19 Pneumonia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Change From Baseline in Combined CD4, CD8, and Monocyte Cell Population in BAL Fluid, as a Percent of Total WBC Population.
研究概览
简要总结
This is a single-blind study of Auxora in patients with critical COVID-19 pneumonia, consisting of up to 3 cohorts of escalating dose. The main goal was to assess pharmacodynamic parameters of immune response, while also assessing safety and tolerability of the drug in this patient population.
详细描述
The primary objective of this study was to assess the pharmacodynamic response of bronchoalveolar lavage (BAL) T cell/monocyte subsets and chemokine release to various doses of Auxora in patients with critical COVID-19 pneumonia. Other objectives included assessment of safety and tolerability of Auxora in patients with critical COVID-19 pneumonia, as well as pharmacokinetic profile of Auxora in these patients. Efficacy was also to be examined based on all-cause mortality at day 60, number of days on mechanical ventilation after randomization, number of days in the hospital after randomization, and number of days in the ICU after randomization.
Patients were randomized 3:1 to Auxora or Placebo. The first 4 patients were enrolled in Cohort 1 (3 Auxora, 1 Placebo). If dose escalation occurred, the next 4 patients were to be enrolled in Cohort 2. If dose escalation occurred again, the next 8 patients were to be enrolled in Cohort 3. The decision to escalate dosing was made by CalciMedica in consultation with the PI and after the review of safety events in Cohorts 1 and 2.
(Note: Trial terminated early after the first patient was enrolled in Cohort 3 due to lack of new Covid-19 hospitalizations.)
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay in any specimen;
- •Moderate ARDS characterized by the following criteria:
- •Invasive mechanical ventilation with a minimum PEEP of 5 cm H2O;
- •PaO2/FiO2 ≤200 that may be estimated from pulse oximetry or determined by arterial blood gas;
- •No evidence of volume overload or heart failure;
- •The patient is ≥18 years of age at the time of consent;
- •QTcF interval ≤ 440 milliseconds;
- •A female patient of childbearing potential must not attempt to become pregnant for 39 months, and if sexually active with a male partner, is willing to practice acceptable methods of birth control for 39 months after the last dose of study drug;
- •A male patient who is sexually active with a female partner of childbearing potential is willing to practice acceptable methods of birth control for 39 months after the last dose of study drug. A male patient must not donate sperm for 39 months;
- •The patient is willing and able to, or has a legal authorized representative (LAR) who is willing and able to, provide informed consent to participate, and to cooperate with all aspects of the protocol.
排除标准
- •Expected survival or time to withdrawal of life-sustaining treatments expected to be <7 days.
- •Suspected septic shock;
- •The patient has a history of:
- •Organ or hematologic transplant;
- •Active hepatitis B or hepatitis C infection;
- •Current treatment with:
- •Chemotherapy;
- •Immunosuppressive medications or immunotherapy (see Section 5.3 for list of prohibited immunosuppressive medications and immunotherapy) at the time of consent;
- •Hemodialysis or Peritoneal Dialysis;
- •The patient is known to be pregnant or is nursing;
- •Currently participating in another study of an investigational drug or therapeutic medical device at the time of consent;
- •Allergy to eggs or any of the excipients in study drug.
研究组 & 干预措施
Auxora
Auxora will be given as a continuous infusion:
Day 1: All 3 cohorts will receive 1.25 mL/kg over 4 hours; After initial infusion is complete, Cohort 3 will receive a continuous infusion of 1.0 mL/kg/24 hours for 96 hours Day 2: Cohort 1 will receive 1.0 mL/kg over 4 hours; Cohort 2 will receive 1.25mL/kg over 4 hours Day 3: Cohort 1 and 2 will receive 1.0 mL/kg over 4 hours Day 4: Cohort 2 will receive 1.0 mL/kg over 4 hours
干预措施: CM4620-IE (Injectable Emulsion) (Drug)
Placebo
Placebo will be given as a continuous infusion:
Day 1: All 3 cohorts will receive 1.25 mL/kg over 4 hours. After initial infusion is complete, Cohort 3 will receive a continuous infusion of 1.0 mL/kg/24 hours for 96 hours Day 2: Cohort 1 will receive 1.0 mL/kg over 4 hours; Cohort 2 will receive 1.25mL/kg over 4 hours Day 3: Cohort 1 and 2 will receive 1.0 mL/kg over 4 hours Day 4: Cohort 2 will receive 1.0 mL/kg over 4 hours
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Combined CD4, CD8, and Monocyte Cell Population in BAL Fluid, as a Percent of Total WBC Population.
时间窗: Baseline Assessment up to 120 hours
Pharmacodynamic endpoint: Assessment of pharmacodynamic response of bronchoalveolar lavage (BAL) T cell/monocyte subsets to Auxora treatment. Flow cytometry was performed on fluid collected from the BAL performed prior to the SFISD (-12 hours) and 24 (±12) hours after completing the last infusion of study drug in Cohorts 1 and 2 and during the final 24 hours of the continuous infusion in Cohort 3. The percentage of total WBC population was assessed for the combined CD4, CD8, and monocyte cell population, and the change between Pre- and Post-Infusion samples (Post value minus Pre value) was reported.
次要结局
- Number of Days Alive and Off Mechanical Ventilation(From randomization until patient is extubated, assessed up to 60 days)
- Change From Baseline in Percent of Immune Cells in BAL Fluid(Baseline Assessment up to 120 hours)
- Number of Patients Alive at Day 60(Randomization through Day 60)
- Number of Days Alive and Out of the Intensive Care Unit (ICU)(From randomization until discharge from ICU, assessed up to 60 days)
- Number of Days Alive and Out of the Hospital(From randomization until discharge from the hospital, assessed up to 60 days)
- Number of Days Alive and Off Mechanical Ventilation(From randomization until patient is extubated, assessed up to 60 days)