64 - A Randomized, Double-Blind, Placebo Controlled Dose Ranging Study of Auxora in Patients with Acute Pancreatitis (AP) and Accompanying Systemic Inflammatory Response Syndrome (SIRS) - CARPO (NCT04681066) (Late-Breaking Abstract)
Robert Sutton BA (Hons), MB, BS, DPhil, FRCS1, Pramod K. Garg MD, DM2, Bechien Wu, MD, MPH3, Sudarshan Hebbar MD4, W. Frank Peacock MD5, Timothy B. Gardner MD, MS, FACG6; 1University of Liverpool, Liverpool, UK, 2Translational Health Science & Technology Institute, Faridabad, India, 3Kaiser Permanente, Los Angeles, CA, 4CalciMedica, La Jolla, CA, 5Baylor College of Medicine, Houston, TX, 6Dartmouth-Hitchcock Medical Center, Lebanon, NH
Introduction: Assess the dose response and efficacy of auxora, a calcium release-activated calcium (CRAC) channel inhibitor, for the treatment of patients presenting with AP and SIRS.
Methods: Patients with acute pancreatitis and >2 SIRS criteria were randomized 1:1:1:1 to 2.0 mg/kg, 1.0 mg/kg, 0.5 mg/kg of auxora, or placebo given intravenously over 4 hours for 3 consecutive days. The primary endpoint was time to solid food tolerance, defined as eating >50% of a >500 calorie low fat solid meal without increased abdominal pain or emesis in the subsequent 2 hours. The key secondary endpoint was severe respiratory failure (defined as invasive mechanical ventilation, or >48 hours of either high flow nasal cannula or noninvasive mechanical ventilation).
Results: Of 216 enrolled, 214 patients received at least 1 study drug dose, 70% in US and 30% in India. The median (interquartile rank; IQR) age was 43 (34, 57) years and median (IQR) time from abdominal pain onset to randomization was 3 (2, 4) days. Overall, 39% were female, etiology was alcohol in 43%, 43% had a high hematocrit, defined as >44 males, >40 females, and 94% had 30 day follow up. The Balthazar score was D or E on enrollment in 145 (68%). In these patients, any dose of auxora had earlier median (IQR) hours to food tolerance: high 66 (26,120), middle 69 (20, 134), and low 69 (27, 181) vs placebo 112 (45, 210). In the high hematocrit group, food tolerance occurred earlier with both high and middle doses, median (IQR) hours of 67 (13, 117) and 64 (20,113), vs both low dose 78 (37, 188) and placebo 114 (41, 187). No patient on high (0/50) or middle dose (0/52) had new onset severe respiratory failure, vs. 4/48 (8.3%) and 4/47 (8.5%) in the low dose and placebo groups, respectively. Generalized multiple comparisons modeling confirmed dose response for solid food tolerance in the high hematocrit group and new onset severe respiratory failure in the total study population. High dose auxora patients had a lower necrotizing pancreatitis rate at 30 days (30%), vs middle (41%) and low (39%) dose auxora, or placebo (37%). 43% of high dose patients had treatment emergent adverse events vs. 47% in placebo. There were no reported suspected or unexpected serious adverse reactions in the trial.
Conclusions: Auxora decreases the time solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients with AP presenting with >2 SIRS criteria.
Disclosures:Robert Sutton: Chair of Steering Committee for CalciMedica’s CARPO trial; Consultant for AbbVie, CalciMedica, Cypralis, Eagle Pharmaceuticals, GlaxoSmithKline (GSK), Graybug, Novartis, Oppenheimer, Perceptive Advisors, Quark Ventures, Recro Pharma, Soleus Capital, Takeda, Vical; Research funding from Calcimedica, Cypralis, EA Pharma, GSK, Eli Lilly, Merck/MSD, Pfizer, UK Medical Research Council, UK National Institute for Health and care Research, EU Innovative Medicines Initiative II, LAP (Liver and Pancreas Research Charity) Research, Chinese Scholarship Council; Drug supply of infliximab for RAPID-I trial (funded by UK NIHR/MRC EME Programme) from Merck/MSD; Collaboration in TransBioLine Consortium (funded by IMI2) with J&J Innovative Medicine, Lilly, Merck/MSD, Novartis, Pfizer, Genentech (Roche) and Sanofi-Aventis; All funds paid to the University of Liverpool and Liverpool University Hospitals NHS Foundation Trust and used for biomedical research; Sudarshan Hebbar: Stock, CalciMedica; Frank Peacock: Research Grants, Abbott, Brainbox, CSL-Vifor, Quidel, Roche, Siemens. Consultant, Abbott, Astra-Zeneca, Biocogniv, Brainbox, Bristol Meyers Squibb, Janssen, Osler, Quidel, Roche, Siemens, Spinchip, Werfen. Stock/Ownership Interests, AseptiScope Inc, Brainbox Inc, Biocogniv, Inc, Braincheck Inc, Coagulo Inc, Comprehensive Research Associates LLC, Comprehensive Research Management Inc, Emergencies in Medicine LLC, Lucia Inc, Prevencio Inc, RCE Technologies, ROMTech, ScPharma, Trivirum Inc, Upstream Inc; All other authors have indicated no relevant financial relationships.
Robert Sutton BA (Hons), MB, BS, DPhil, FRCS, Pramod K. Garg MD, DM, Bechien Wu, MD, MPH, Sudarshan Hebbar MD, W. Frank Peacock MD, Timothy B. Gardner MD, MS, FACG, 64, A Randomized, Double-Blind, Placebo Controlled Dose Ranging Study of Auxora in Patients with Acute Pancreatitis (AP) and Accompanying Systemic Inflammatory Response Syndrome (SIRS)- CARPO (NCT04681066) (late-breaking abstract), ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.
