CM4620 Injectable Emulsion Versus Supportive Care in Patients With Acute Pancreatitis and SIRS
Condition: Acute Pancreatitis; Systemic Inflammatory Response Syndrome
MeSH terms: Pancreatitis; Syndrome; Systemic Inflammatory Response Syndrome
Intervention: CM4620 Injectable Emulsion (Low Dose); CM4620 Injectable Emulsion (High Dose)
Intervention description: CM4620-IE 1.0 mg/kg on Day 1 and then 1.4 mg/kg on Days 2-4, during the first phase of the study (Cohorts 1 and 2). All doses of CM4620-IE will be administered intravenously (IV) over 4 hours.; CM4620-IE 2.08 mg/kg on Days 1 and 2 and then 1.6 mg/kg on Days 3 and 4, during the second phase of the study (Cohorts 3 and 4). All doses of CM4620-IE will be administered intravenously (IV) over 4 hours.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Diagnosis of acute pancreatitis established by the presence of abdominal pain
             consistent with acute pancreatitis and 1 of the following 2 criteria:

               1. Serum lipase and/or serum amylase > 3 times the upper limit of normal (ULN);

               2. Characteristic findings of acute pancreatitis on abdominal imaging;

          2. A SpO2 <96% with a FiO2 of 21% (room air) to 27%, or a SpO2 <97% with a FiO2 ≥28%;

          3. Diagnosis of SIRS, defined by the presence of at least 2 of the following 4 criteria:

               1. Temperature < 36°C or > 38°C;

               2. Heart rate > 90 beats/minute;

               3. Respiratory rate >20 breaths/minute or arterial carbon dioxide tension (PaCO2)
                  <32 mmHg;

               4. White blood cell count (WBC) >12,000 mm3, or <4,000 mm3, or > 10% immature (band)
                  forms;

          4. 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;

          5. Adults ≥ 18 years of age;

          6. 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;

          7. 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.

          8. 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:

          1. 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;

          2. Suspected presence of cholangitis in the judgment of the treating investigator;

          3. ERCP performed in the previous 7 days;

          4. Any malignancy being treated with chemotherapy or immunotherapy;

          5. Any autoimmune disease being treated with immunosuppressive medication or
             immunotherapy;

          6. History of:

               1. Acute pancreatitis with pancreatic necrosis on Contrast-Enhanced Computed
                  Tomography (CECT) of the pancreas;

               2. Chronic pancreatitis, pancreatic necrosis or necrosectomy, or pancreatic enzyme
                  replacement therapy;

               3. Biopsy proven cirrhosis, portal hypertension, hepatic failure/hepatic
                  encephalopathy;

               4. Known hepatitis B or C, or HIV;

               5. History of organ or hematologic transplant;

               6. Resuscitated cardiac arrest, myocardial infarction, revascularization,
                  cardiovascular accident (CVA) in the 30 days prior to Day 1;

          7. Current renal replacement therapy;

          8. Current known abuse of cocaine or methamphetamine;

          9. Known to be pregnant or are nursing;

         10. Participated in another study of an investigational drug or therapeutic medical device
             in the 30 days prior to Day 1;

         11. History of allergy to eggs or known hypersensitivity to any components of CM4620-IE.