CM4620 Injectable Emulsion Versus Supportive Care in Patients With Acute Pancreatitis and SIRS

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.