A Study of Auxora in Patients With Acute Pancreatitis and Accompanying SIRS
A Study of Auxora in Patients With Acute Pancreatitis and Accompanying SIRS
Approximately 216 patients with acute pancreatitis and accompanying SIRS will be randomized
 at approximately 30 sites. Patients will be randomly assigned to either Auxora at one of
 three dose levels or one of three placebo volumes to maintain the double-blind. Study drug
 infusions will occur every 24 hours for three consecutive days for a total of three
 infusions. Patients will remain hospitalized as per standard of care and once discharged will
 be asked to complete a daily meal diary and return for a Day 30 safety assessment. It is
 recommended that patients randomized in the study should not be discharged from the hospital
 until solid food is tolerated, abdominal pain has resolved or been adequately controlled, and
 there is no clinical evidence of infection.
This double blind, randomized, placebo-controlled study will evaluate the efficacy, safety,
 and tolerability of three different dose levels of Auxora in patients with acute pancreatitis
 and accompanying SIRS.

 Approximately 216 patients will be randomized 1:1:1:1 into one of 4 groups using a computer
 generated randomization scheme accessed through an interactive voice/web response system
 (IXRS). Randomization will be first stratified by gender (male or female) and then by risk
 for organ failure in the gender subgroups (higher or lower). Higher risk for organ failure is
 defined by the presence of both an elevated hematocrit (HCT ≥44% for men or ≥40% for women)
 and hypoxemia (imputed PaO2/FiO2 ≤360). Lower risk for organ failure is defined by the
 absence of either or both an elevated hematocrit and hypoxemia. The PaO2/FiO2 will be
 determined using an arterial blood gas or imputed using pulse oximetry.

 All patients will have received a Screening CECT of the abdomen/pancreas before being
 randomized into the study. CECTs performed as standard of care may be used as the Screening
 CECT but must have been performed in the 12 hours before Consent or after Consent and before
 Randomization.

 The Start of First Infusion of Study Drug (SFISD) should occur within 8 hours of the patient
 or LAR providing informed consent. Patients randomized to Group 1 will receive 2.0 mg/kg of
 Auxora intravenously every 24 hours (±1 hour) for a total of three doses. Patients randomized
 to Group 2 will receive 1.0 mg/kg of Auxora intravenously every 24 hours (±1 hour) for a
 total of three doses. Patients randomized to Group 3 will receive 0.5 mg/kg of Auxora
 intravenously every 24 hours (±1 hour) for a total of three doses. Patients randomized to
 Group 4 will receive emulsion without any active pharmaceutical ingredient. Patients in Group
 4 will receive one of three randomly assigned dose volumes, 1.25 mL/kg, 0.625 mL/kg, or
 0.3125 mL/kg, which will be administered intravenously every 24 hours (±1 hour) for a total
 of three doses. The dosing will be based on actual body weight obtained at the time of
 hospitalization or screening for the study. As described in the pharmacy manual, the upper
 limit of the volume of Auxora and volume of Placebo that will be administered will be 156.25
 mL. The sponsor, investigators and patients will be blinded to the assigned group. In the
 event of a medical emergency, investigators will be able to receive the treatment assignment
 if required to provide optimal care of the patient.

 For all 4 groups, a study physician or appropriately trained delegate will perform
 assessments at screening, at the baseline assessment, immediately prior to the SFISD, and
 then every 24 hours until 240 hours after the SFISD, or until discharge if earlier. If
 patients remain hospitalized at Day 12, assessments will then be performed every 48 hours
 starting on Day 12 until Day 28, or until discharge if earlier. Patients discharged from the
 hospital before Day 25 will return at Day 30 (+5 days) to perform the Day 30 assessments. If
 patients are discharged on Days 25-29, the Day 30 assessments may be performed prior to
 discharge.

 Patients will receive another CECT of the abdomen/pancreas at the Day 30 (±5 days) visit. All
 CECTs performed as standard of care after randomization and before the Day 30 CECT will also
 be captured. A blinded central reader will read the Screening, Day 30, and any standard of
 care CECTs obtained between randomization and 30 days.

 Patients will complete the modified American Neurogastroenterology and Motility Society
 Gastrointestinal Cardinal Symptom Index Daily Diary (mGCSI-DD) worksheet at the baseline
 assessment, at 96 hours, 168hours, Day 14 and Day 21 (for patients who remain hospitalized on
 these days), on the day of discharge, and daily at bedtime after discharge until the Day 30
 visit. Patients who are discharged on Days 25-29 will not complete the mGCSI worksheet after
 discharge.

 It is recommended that all patients randomized in the study should receive care consistent
 with the 2018 American Gastroenterological Association (AGA) Institute Technical Review of
 the Initial Medical Management of Acute Pancreatitis. Patients should receive local standard
 of care (SOC) for the management of other medical conditions.

 In patients with acute pancreatitis, the AGA strongly recommends early oral feeding (within
 24 hours) rather than keeping the patient nil per mouth (Nil per Os, NPO). Patients
 randomized into the study, therefore, will be offered a low fat, ≥500-calorie solid meal at
 each mealtime after the infusion of the first dose of study drug if alert and not on
 mechanical ventilation. If the patient does not wish to eat the solid meal when offered or is
 unable to tolerate the solid meal, they should then be offered a liquid meal. The same
 approach should occur at each subsequent mealtime. When patients eat a solid meal, it should
 be recorded if they ate ≥50% of the meal and if they either vomited or experienced an
 increase in abdominal pain in the two hours after eating a meal.

 It is also recommended that all patients randomized in the study should not be discharged
 from the hospital until solid food is tolerated, abdominal pain has resolved or been
 adequately controlled, and there is no clinical evidence of infection. Tolerating solid food
 is defined as eating ≥50% of a low fat, ≥500-calorie solid meal without an increase in
 abdominal pain or vomiting. If the patient is not tolerating either solid or liquid meals,
 tube feedings should be considered.

 All protocol required laboratory testing, except biomarker and PK samples, will be performed
 at the local laboratory. Results from the biomarkers and PK blood samples collected as part
 of the protocol and being tested at a central lab will not be available to assist the PI or
 treating physician in managing the patient.
Inclusion Criteria:

 All of the following must be met for a patient to be randomized into the study:

 1. The diagnosis of acute pancreatitis has been established by the presence of abdominal
 pain consistent with acute pancreatitis together with at least 1 of the following 2
 criteria:

 1. Serum lipase > 3 times the upper limit of normal (ULN);

 2. Characteristic findings of acute pancreatitis on abdominal imaging;

 2. The diagnosis of SIRS has been established by the presence of at least two of the
 following four 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;

 3. At least one of the following criteria is also present:

 1. A peripancreatic fluid collection or a pleural effusion on a contrast-enhanced
 computed tomography (CECT) performed in the 12 hours before Consent or after
 Consent and before Randomization;

 2. Abdominal examination documenting either abdominal guarding or rebound
 tenderness;

 3. Hematocrit ≥44% for men or ≥40% for women;

 4. The patient is ≥ 18 years of age;

 5. Lack of pancreatic necrosis, pancreatic calcifications, pancreatic pseudocysts and no
 evidence for previous necrosectomy or pancreatic surgery identified by CECT performed
 in the 12 hours before Consent or after Consent and before Randomization;

 6. A female patient of childbearing potential who is sexually active with a male partner
 is willing to practice acceptable methods of birth control for 180 days after the last
 dose of study drug. A female patient must not attempt to become pregnant for 180 days;

 7. A male patient who is sexually active with a female partner of childbearing potential
 is willing to practice acceptable methods of birth control for 180 days after the last
 dose of study drug. A male patient must not donate sperm for 180 days;

 8. 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.

 Exclusion Criteria:

 Patients with any of the following conditions or characteristics must be excluded from
 randomizing:

 1. Expected survival <6 months;

 2. Suspected presence of cholangitis in the judgment of the treating physician;

 3. The patient has a known history of:

 1. Organ or hematologic transplant;

 2. HIV, hepatitis B, or hepatitis C infection;

 3. Chronic pancreatitis;

 4. Current treatment with:

 1. Chemotherapy;

 2. Immunosuppressive medications or immunotherapy

 3. Pancreatic enzyme replacement therapy;

 4. Hemodialysis or Peritoneal Dialysis;

 5. The patient is known to be pregnant or is nursing;

 6. The patient has participated in another study of an investigational drug or
 therapeutic medical device in the 30 days before randomization;

 7. Allergy to eggs or known hypersensitivity to any components of study drug.