Auxora for the Treatment of Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome: Clinical Development of a Calcium Release-Activated Calcium Channel Inhibitor

Abstract

Objectives: To assess the safety of Auxora in patients with acute pancreatitis (AP), systemic inflammatory response syndrome (SIRS), and hypoxemia, and identify efficacy endpoints to prospectively test in future studies.

Methods: This phase 2, open-label, dose-response study randomized patients with AP, accompanying SIRS, and hypoxemia (n = 21) to receive low-dose or high-dose Auxora plus standard of care (SOC) or SOC alone. All patients received pancreatic contrast-enhanced computed tomography scans at screenings, day 5/discharge, and as clinically required 90 days postrandomization; scans were blinded and centrally read to determine AP severity using computed tomography severity index. Solid food tolerance was assessed at every meal and SIRS every 12 hours.

Results: The number of patients experiencing serious adverse events was not increased with Auxora versus SOC alone. Three (36.5%) patients with moderate AP receiving low-dose Auxora improved to mild AP; no computed tomography severity index improvements were observed with SOC. By study end, patients receiving Auxora better tolerated solid foods, had less persistent SIRS, and had reduced hospitalization versus SOC.

Conclusions: The favorable safety profile and patient outcomes suggest Auxora may be an appropriate early treatment for patients with AP and SIRS. Clinical development will continue in a randomized, controlled, blinded, dose-ranging study.

Trial registration: ClinicalTrials.gov NCT03401190.

Conflict of interest statement

J.M. reports grants from CalciMedica, Inc. during the conduct of the study; and grants from CalciMedica, Inc. and Abbott Labs outside of the present work. K.S. and S.H. are employees of, and hold stock in, CalciMedica, Inc. C.B., J.W., C.M., T.L.B. declare no conflict of interest.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

FIGURE 1

Patient enrollment and randomization. The patient in the high-dose Auxora arm who died developed multiorgan failure with acute respiratory distress syndrome and renal failure had discontinued Aurora prior to his death. The SAEs and cause of death were considered to be unrelated to study drug; survival time for this patient was 18.3 days. *The 2 patients who discontinued the study drug remained in study and were followed through the 90-day assessment or death. One patient died before the 90-day assessment. The other patient who discontinued the study drug completed the 30- and 90-day assessment. SOC, standard of care.

FIGURE 2

Change in acute pancreatitis from screening to day 5 or discharge based on CTSI score by CECT scans. Severity of acute pancreatitis was determined by CTSI scores according to CECT scans at screening, day 5 or discharge, or as needed over the 90-day period as required for patient care. One patient treated with high-dose Auxora did not receive a CTSI score at either screening or day 5/discharge and 1 patient treated with standard of care alone did not receive a CTSI score at screening because contrast was not given; at day 5/discharge, this patient was noted as having mild acute pancreatitis. AP, acute pancreatitis.

FIGURE 3

Percentage of patients tolerating a solid diet overtime. The ability to tolerate a solid diet was defined as tolerating ≥50% of solid meal without vomiting or an increase in abdominal pain.