Trial Outcomes & Findings for A Study of Auxora in Patients With Acute Pancreatitis and Accompanying SIRS (NCT NCT04681066)

A Study of Auxora in Patients With Acute Pancreatitis and Accompanying SIRS

Time to Solid Food Tolerance (TSFT): Number of hours from date/time of SFISD to date/time patient receives a solid meal that is tolerated, defined as eating \>/=50% of a low fat \>/= 500-calorie solid meal w/o increase in abdominal pain or vomiting within 2 hours of mealtime. If patient was discharged w/o tolerating solid food, the daily record of the modified ANMS Gastrointestinal Cardinal Symptom Index Daily Diary (mGCSI-DD) at or after hospital discharge was used to calculate TSFT. For these patients, TSFT date/time was considered to be 8am on the first of 3 consecutive days where the following criteria were met in mGCSI-DD: no vomiting, no or mild nausea, no or mild inability to finish a normal sized meal, no or mild abdominal pain. gMCP-Mod: Generalized Multiple Comparisons and Modeling--3 steps: 1) Hazard ratio (dose vs placebo) using stratified Cox regression w/ stratification by sex and hematocrit (high/low). 2) Multiple contrast test. 3) Find best-fit dose-response model.

Analysis of patients without respiratory failure at the time of randomization (defined as a P/F ratio ≤300 measured by an arterial blood gas or imputed from pulse oximetry) who later developed severe respiratory failure during the course of the study.

The incidence, severity and duration of organ failure was defined by the development of severe respiratory failure or severe renal failure or severe cardiac failure. The proportion of patients who developed each type of organ failure, or multi-organ failure (more than 1 organ failure), was analyzed.

Number (and percentage) of patients who tolerated solid food at 48hrs, 72hrs, and 96hrs from start of first infusion of study drug, as well as at time of first discharge from hospital

The time (in hours) to medically indicated discharge, defined as the number of days from the SFISD to the first date of meeting the criteria below: * the patient tolerated solid food, as defined by the main analytical approach; and * abdominal pain was controlled or resolved, which was defined by a reduction in pain, as assessed by the PNRS scale, of ≥50% from the peak level in the first 24 hours and no use of opioids; and * no clinical evidence of an infection requiring continued hospitalization. Kaplan-Meier (K-M) estimates of median time to medically indicated discharge are shown.

Number of days in the hospital during the first 30 Days of the Study from the SFISD (start of first infusion of study drug) while still alive, for any reason. Includes ICU stay and readmissions. The number of days in the hospital before the patient's death was used in the analysis.(Note: there was only 1 patient death in this study, in the 1.0 mg/kg Auxora group)

The proportion of patients who were re-hospitalized for either acute pancreatitis, or the development of pancreatic necrosis/necrotizing pancreatitis through the Day 30 visit.

Independent reviewers performed a blinded central review of Contrast Enhanced Computed Tomography (CECT) imaging data, or MRI imaging data, obtained at the Screening and Day 30 visits to assess the Computed Tomography Severity Index (CTSI). Review was performed by two independent radiologists (primary review) using a consensus methodology. The CTSI scoring uses a combination of Balthazar score grading of pancreatitis (A-E) and grading the extent of pancreatic necrosis (none, ≤30%, \>30-50%, or \>50%) to designate AP as mild, moderate, or severe. Proportion of patients with moderate or severe AP by CTSI score at baseline who became mild AP at Day 30, and the proportion of patients with mild AP by CTSI at baseline who had moderate or severe AP at Day 30 were analyzed.

Development of pancreatic necrosis ≥30% and \>50% in patients who had no pancreatic necrosis at screening (Note: There were no patients with pancreatic necrosis at screening in any of the treatment groups.)

The proportion of patients who developed persistence of SIRS ≥48 Hours after the SFISD analyzed through Day 30. If the patient was discharged before 48 Hours after the SFISD, the last available post-treatment data was used to define the SIRS status at 48 hours after the SFISD based on the LOCF method.

Mortality was assessed from randomization through Day 30

Mean change in Pain Numeric Rating Score (PNRS) from baseline (time of screening). In patients who were able to self-report their pain, the PNRS was used to grade the severity of the abdominal pain. Patients were asked, "On a scale of 0 to 10, with 0 being no pain at all and 10 being the worst pain imaginable, how would you rate your pain RIGHT NOW." It was also recorded if an opioid analgesic had been given in the 2 hours prior to the PNRS determination.

The win ratio compares effectiveness of each Auxora dose group with the placebo group. It is calculated by dividing the total number of wins by the total number of losses, with a win ratio \>1 indicating better outcomes for Auxora treatment. Comparison between placebo and Auxora outcomes was performed in a hierarchical manner, in the following order: 1. Mortality (see Outcome Measure 11), 2. New Onset Severe Respiratory Failure (see Outcome Measure 2), 3. New Onset Necrotizing Pancreatitis at Day 30 (see Outcome Measure 18), and 4. Time to Medically Indicated Discharge (see Outcome Measure 5). Stratification was performed by sex (male or female) and then by HCT (higher or lower). Subjects with respiratory failure at baseline were imputed as a non-event. Subjects with missing necrotizing pancreatitis evaluation or positive necrotizing pancreatitis at screening were imputed as a non-event. Subjects missing a necrotizing pancreatitis evaluation at Day 30 were imputed as a non-event.

Exploratory. Percentage of Patients with Infected Pancreatic Necrosis at Day 30 after SFISD.

Exploratory. Count of patients who experienced sepsis after SFISD.

Exploratory analysis of serum biomarkers.

Exploratory analysis of urine biomarker NGAL

The number of patients who had no necrotizing pancreatitis at screening, and developed any amount of necrotizing pancreatitis based on the Day 30 visit CECT reading results.