An Open-Label, Dose-Response Study of CM4620 Injectable Emulsion (CM4620-IE) in Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome (SIRS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 9
- 主要终点
- The Safety and Tolerability of CM4620-IE in Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome (SIRS) or Hypoxemia.
研究概览
简要总结
This open-label, dose-response study will evaluate the safety and efficacy of CM4620-IE in patients with acute pancreatitis and accompanying SIRS. The study will consist of two phases. The first phase will consist of 4 female and 4 male patients (cohorts 1 and 2, respectively), enrolled concurrently, randomized in a 3:1 ratio to receive CM4620-IE plus standard of care versus standard of care alone. Planned doses for first phase will be CM4620-IE 1.0 mg/kg on Day 1 and then 1.4 mg/kg on Days 2 - 4.
The second phase will consist of 8 female and 8 male patients (cohorts 3 and 4, respectively), enrolled concurrently, randomized in a 3:1 ratio to receive CM4620-IE plus standard of care versus standard of care alone. Planned doses for second phase will be CM4620-IE 2.08 mg/kg on Days 1 and 2 and then 1.6 mg/kg on Days 3 and 4. Dose escalation to second phase would only occur if needed for efficacy reasons and if no events suggesting a safety signal would occur with higher dosing.
The study is not powered for the analysis of study data with inferential statisitcs as the primary purpose of the study is to explore what endpoints would be most appropriate for future trials.
详细描述
After review of the efficacy, tolerability and safety data from cohorts 1 and 2 by the sponsor and the United States Food and Drug Administration, the decision was made to continue the low-dose regimen (CM4620-IE 1.0 mg/kg on Day 1 and then 1.4 mg/kg on Days 2 - 4) in cohort 3. Cohort 4 received the high-dose regimen (CM4620-IE 2.08 mg/kg on Days 1 and 2 and then 1.6 mg/kg on Days 3 and 4) as planned. Efficacy analysis were combined because no dose escalation occurred in cohort 3.
Patients were followed for 90 days after randomization.
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
- None
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
- •Diagnosis of acute pancreatitis established by the presence of abdominal pain consistent with acute pancreatitis and 1 of the following 2 criteria:
- •Serum lipase and/or serum amylase > 3 times the upper limit of normal (ULN);
- •Characteristic findings of acute pancreatitis on abdominal imaging;
- •A SpO2 <96% with a FiO2 of 21% (room air) to 27%, or a SpO2 <97% with a FiO2 ≥28%;
- •Diagnosis of SIRS, defined by the presence of at least 2 of the following 4 criteria:
- •Temperature < 36°C or > 38°C;
- •Heart rate > 90 beats/minute;
- •Respiratory rate >20 breaths/minute or arterial carbon dioxide tension (PaCO2) <32 mmHg;
- •White blood cell count (WBC) >12,000 mm3, or <4,000 mm3, or > 10% immature (band) forms;
- •No evidence of pancreatic necrosis on contrast-enhanced computed tomography (CECT performed in the 18 hours prior to consent or after consent and before Day 1;
- •Adults ≥ 18 years of age;
- •A female patient of child bearing potential who is sexually active with a male partner must be willing to practice acceptable methods of birth control for 365 days after the last dose of CM4620-IE;
- •A male patient who is sexually active with a female partner of childbearing potential must be willing to practice acceptable methods of birth control for 365 days after the last dose of CM4620-IE and must not donate sperm for 365 days.
- •Willing and able to, or have a legal authorized representative (LAR) that is willing and able to, provide informed consent to participate, and to cooperate with all aspects of the protocol.
排除标准
- •Any concurrent clinical condition that a study physician believes could potentially pose an unacceptable health risk to the patient while involved in the study, including a CV SOFA score of 4 at the time of screening, or may limit expected survival to <6 months;
- •Suspected presence of cholangitis in the judgment of the treating investigator;
- •ERCP performed in the previous 7 days;
- •Any malignancy being treated with chemotherapy or immunotherapy;
- •Any autoimmune disease being treated with immunosuppressive medication or immunotherapy;
- •History of:
- •Acute pancreatitis with pancreatic necrosis on Contrast-Enhanced Computed Tomography (CECT) of the pancreas;
- •Chronic pancreatitis, pancreatic necrosis or necrosectomy, or pancreatic enzyme replacement therapy;
- •Biopsy proven cirrhosis, portal hypertension, hepatic failure/hepatic encephalopathy;
- •Known hepatitis B or C, or HIV;
- •History of organ or hematologic transplant;
- •Resuscitated cardiac arrest, myocardial infarction, revascularization, cardiovascular accident (CVA) in the 30 days prior to Day 1;
- •Current renal replacement therapy;
- •Current known abuse of cocaine or methamphetamine;
- •Known to be pregnant or are nursing;
- •Participated in another study of an investigational drug or therapeutic medical device in the 30 days prior to Day 1;
- •History of allergy to eggs or known hypersensitivity to any components of CM4620-IE.
研究组 & 干预措施
Low Dose Group
Phase 1: Cohorts 1 & 2 will consist of 4 female and 4 male patients enrolled concurrently who will be randomized 3:1 to receive CM4620-IE plus standard of care versus standard of care alone. Planned doses for patients who are randomized to receive CM4620-IE are 1.0 mg/kg on Days 1 and 1.4 mg/kg on Days 2-4.
干预措施: CM4620 Injectable Emulsion (Low Dose) (Drug)
High Dose Group
Phase 2: Cohorts 3 & 4 will consist of 8 female and 8 male patients enrolled concurrently who will be randomized 3:1 to receive CM4620-IE plus standard of care versus standard of care alone. Planned doses for patients who are randomized to receive CM4620-IE are 2.08 mg/kg of CM4620-IE on Days 1 and 2, and 1.6 mg/kg on Days 3 and 4.
干预措施: CM4620 Injectable Emulsion (High Dose) (Drug)
结局指标
主要结局
The Safety and Tolerability of CM4620-IE in Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome (SIRS) or Hypoxemia.
时间窗: 90 Days
Safety and tolerability will be assessed by monitoring the frequency, duration and severity of treatment-emergent adverse events (TEAEs) throughout the study period.
次要结局
- Median Days in Hospital(discharge)
- The Number of Patients With a Change in Computed Tomography Severity Index (CTSI) Score Between Screening and Day 5 (or Discharge, if Earlier)(5 days (or discharge, if earlier))
- The Number of Patients Tolerating Solid Food(at Day 10 (or discharge, if earlier))
- Percentage of Patients With Persistent Systemic Inflammatory Response Syndrome (SIRS)(≥ 48 hours)
- IL-6 Values in Patients With a Maximum IL-6 Value ≥ 150 pg/mL in the First 24 Hours(Day 10 (or discharge, if earlier))