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

• ClinicalTrials.gov Identifier: NCT04681066
• Recruitment Status: Recruiting
• First Posted: December 23, 2020
• Last Update Posted: June 7, 2023
• Sponsor: CalciMedica, Inc.
• Information provided by (Responsible Party): CalciMedica, Inc.

Study Description

Brief Summary:

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 necessitating continued hospitalization.

Condition or disease	Intervention/treatment	Phase
Acute Pancreatitis; Systemic Inflammatory Response Syndrome	Drug: CM-4620 Injectable Emulsion or CM-4620-IE; Other: Placebo	Phase 2

Detailed Description:

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 24 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 the Day 30 visit.

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, or if not NPO for a planned surgey/medical procedure, or if not NPO because of an acute medical condition. 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 216 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Matching placebo
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo Controlled Dose-Ranging Study of Auxora in Patients With Acute Pancreatitis and Accompanying Systemic Inflammatory Response Syndrome
• Actual Study Start Date: March 24, 2021
• Estimated Primary Completion Date: September 2024
• Estimated Study Completion Date: September 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 2.0 mg/kg (1.25 mL/kg); administered intravenously over 4 hours at a constant rate of infusion. They will be administered every 24 hours (±1 hours) for three consecutive days for a total of 3 doses.	Drug: CM-4620 Injectable Emulsion or CM-4620-IE; Auxora is to be administered as an IV infusion and is supplied as a translucent, white to yellowish colored, sterile, non-pyrogenic emulsion containing 1.6 mg/mL of the active pharmaceutical ingredient CM4620. CM4620-IE is supplied as an 80 mL fill in a 100 mL, single-use glass vial. The drug product is formulated as an emulsion due to the low solubility of CM4620 in aqueous solution. CM4620-IE contains egg phospholipids, medium chain triglycerides, glycerin, edetate disodium salt dehydrate (EDTA), sodium hydroxide (as needed to adjust pH), and sterile water for injection.; Other Name: Auxora
Active Comparator: 1.0 mg/kg (0.625 mL/kg); administered intravenously over 4 hours at a constant rate of infusion. They will be administered every 24 hours (±1 hours) for three consecutive days for a total of 3 doses.	Drug: CM-4620 Injectable Emulsion or CM-4620-IE; Auxora is to be administered as an IV infusion and is supplied as a translucent, white to yellowish colored, sterile, non-pyrogenic emulsion containing 1.6 mg/mL of the active pharmaceutical ingredient CM4620. CM4620-IE is supplied as an 80 mL fill in a 100 mL, single-use glass vial. The drug product is formulated as an emulsion due to the low solubility of CM4620 in aqueous solution. CM4620-IE contains egg phospholipids, medium chain triglycerides, glycerin, edetate disodium salt dehydrate (EDTA), sodium hydroxide (as needed to adjust pH), and sterile water for injection.; Other Name: Auxora
Active Comparator: 0.5 mg/kg (0.3125 mL/kg); administered intravenously over 4 hours at a constant rate of infusion. They will be administered every 24 hours (±1 hours) for three consecutive days for a total of 3 doses.	Drug: CM-4620 Injectable Emulsion or CM-4620-IE; Auxora is to be administered as an IV infusion and is supplied as a translucent, white to yellowish colored, sterile, non-pyrogenic emulsion containing 1.6 mg/mL of the active pharmaceutical ingredient CM4620. CM4620-IE is supplied as an 80 mL fill in a 100 mL, single-use glass vial. The drug product is formulated as an emulsion due to the low solubility of CM4620 in aqueous solution. CM4620-IE contains egg phospholipids, medium chain triglycerides, glycerin, edetate disodium salt dehydrate (EDTA), sodium hydroxide (as needed to adjust pH), and sterile water for injection.; Other Name: Auxora
Placebo Comparator: Placebo (1.25, 0.625, or 0.3125 mL/kg); patients randomized to placebo will receive one of three following volumes (1.25 mL/kg, 0.625 mL/kg, and 0.3125 mL/kg. although three volumes - all patients randomized to placebo will be analyzed together as one arm. administered intravenously over 4 hours at a constant rate of infusion. They will be administered every 24 hours (±1 hours) for three consecutive days for a total of 3 doses.	Other: Placebo; Matching Placebo is to be administered as an IV infusion and is supplied as a translucent, white to yellowish, sterile, non-pyrogenic emulsion carrier containing no active pharmaceutical ingredient. Placebo is supplied as an 80 mL fill in a 100 mL single-use vial. Placebo contains the same ingredients as Auxora except that it does not contain CM4620.

Outcome Measures

Primary Outcome Measures :

1. Time to solid food tolerance [ Time Frame: from start of first infusion of study drug (SFISD) to day 30 ]
   Defined as the number of hours from the date and time of the start of the first infusion of study (SFISD) for the patient to the date and time the patient receives a solid meal that is tolerated

Secondary Outcome Measures :

1. Solid food tolerance [ Time Frame: from SFISD to 48 hours, 72 hours and 96 hours and at time of hospital discharge ]
2. Time to medically indicated discharge [ Time Frame: from start of first infusion of study drug and through time of hospital discharge or through Day 30, whichever occurs first ]
3. Length of stay in the hospital [ Time Frame: from admission date into the hospital until discharge date from the hospital ]
4. Length of stay in the ICU for patients admitted to the ICU [ Time Frame: from admission into ICU until discharge from ICU ]
5. Re-hospitalization for acute pancreatitis by Day 30 [ Time Frame: time from initial date of hospital discharge through date of re-hospitalization through day 30 ]
6. Change in severity of acute pancreatitis by CTSI score from screening to Day 30 [ Time Frame: from informed consent through day 30 ]
7. Development of pancreatic necrosis ≥30% and >50% [ Time Frame: from enrollment CECT through Day 30 CECT ]
8. The persistence of SIRS ≥48 hours after the SFISD [ Time Frame: from SFISD through day 30 ]
9. Incidence, severity, and duration of organ failure [ Time Frame: from enrollment and through day 30 ]
10. Mortality by Day 30 [ Time Frame: from randomization and through day 30 ]
11. Change in pain score [ Time Frame: from enrollment through day 30 ]
12. Change in opioid use [ Time Frame: from enrollment through day 30 ]

Other Outcome Measures:

1. Development of infected pancreatic necrosis [ Time Frame: from enrollment CECT through Day 30 CECT ]
   Exploratory
2. Development of sepsis [ Time Frame: from randomization through day 30 ]
   Exploratory
3. Hospital procedures for the management of pancreatic necrosis [ Time Frame: from randomization through day 30 ]
   Exploratory
4. Change in GCSI-DD score [ Time Frame: from randomization through day 30 ]
   Exploratory
5. Change in albumin [ Time Frame: from randomization through day 30 ]
   Exploratory
6. Change in ANC/ALC ratio and IL-6 levels [ Time Frame: from randomization through day 30 ]
   Exploratory
7. Change in urine NGAL [ Time Frame: from randomization through day 30 ]
   Exploratory

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: self-reported gender
• Accepts Healthy Volunteers: No

Criteria

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 24 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 24 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.

Contacts and Locations

Contacts

Contact: Liisa Tingue; 9725231073; liisa@calcimedica.com

Locations

United States, Arkansas

University of Arkansas; Not yet recruiting

Little Rock, Arkansas, United States, 72205

Contact: Sumant Inamdar, MD, PhD SInamdar@uams.edu

Principal Investigator: Sumant Inamdar, MD, PhD

United States, California

Long Beach Medical Center; Recruiting

Long Beach, California, United States, 90806

Contact: Alexis Suarez 562-760-7221 ASuarez2@memorialcare.org

Principal Investigator: Fady Youssef, MD

Kaiser Permanente Los Angeles Medical Center; Recruiting

Los Angeles, California, United States, 90027

Contact: Edna Halilbegovic 626-372-1577 Edna.X.Halilbegovic@kp.org

Principal Investigator: Bechien Wu, MD

LA County Hospital - USC; Recruiting

Los Angeles, California, United States, 90033

Contact: Alejandro Vazquez Alejandro.Vazquez@med.usc.edu

Principal Investigator: James Buxbaum, MD

UCLA Ronald Reagan Medical Center; Recruiting

Los Angeles, California, United States, 90095

Contact: Melissa Arevalo MFArevalo@mednet.ucla.edu

Principal Investigator: Edward Livingston, MD

University of California at Irvine Medical Center; Recruiting

Orange, California, United States, 92868

Contact: Cesar Figueroa 714-509-2487 figuercl@hs.uci.edu

Principal Investigator: Jason Samarasena, MD

Harbor UCLA Medical Center; Recruiting

Torrance, California, United States, 90502

Contact: Dyonne Tetangco 424-571-7635 d.tetangco@lundquist.org

Principal Investigator: Brant Putnam, MD

Torrance Memorial Medical Center; Recruiting

Torrance, California, United States, 90505

Contact: Joy Gonzalez HernaJoy.Gonzalez@tmmc.com

Principal Investigator: James McKinnell, MD

United States, Colorado

National Jewish Health; Withdrawn

Denver, Colorado, United States, 80206

United States, Connecticut

Yale University School of Medicine; Withdrawn

New Haven, Connecticut, United States, 06510

The Stamford Hospital; Completed

Stamford, Connecticut, United States, 06902

United States, Florida

Sarasota Memorial Health Care System; Recruiting

Sarasota, Florida, United States, 34239

Contact: Tamela Fonseca, MSN, RN 941-228-1752 Tamela-Fonseca@smh.com

Principal Investigator: Ibrahim Saad, MD

Tampa General Hospital; Recruiting

Tampa, Florida, United States, 33606

Contact: Ashley Barnes, BSN, RN 813-660-6035 ashleynbarnes@tgh.org

Principal Investigator: Jason Wilson, MD

United States, Idaho

St. Luke's Regional Medical Center; Recruiting

Boise, Idaho, United States, 83712

Contact: Summer Reames, MPH 208-381-8907 reamess@slhs.org

Principal Investigator: Karen Miller, MD

United States, Illinois

Northwestern University Hospital; Recruiting

Chicago, Illinois, United States, 60611

Contact: Thomas Li 312-472-9597 thomasli@northwestern.edu

Principal Investigator: Raj Keswani, MD

United States, Kentucky

Robley Rex VA Medical Center; Recruiting

Louisville, Kentucky, United States, 40206

Contact: Anne Marie Webb anne.webb@louisville.gov

Principal Investigator: Gerald Dryden, MD

United States, Maryland

Lumunis Health Anne Arundel Medical Center; Withdrawn

Annapolis, Maryland, United States, 21401

University of Maryland; Recruiting

Baltimore, Maryland, United States, 21201

Contact: Kyra Lasko Kyra.lasko@som.umaryland.edu

Principal Investigator: R. Gentry Wilkerson, MD

United States, Michigan

Henry Ford Health System; Recruiting

Detroit, Michigan, United States, 48202

Contact: Kathleen Wilson 313-916-9551 kwilso10@hfhs.org

Principal Investigator: Joseph Miller, MD

United States, Minnesota

Methodist Hospital; Recruiting

Saint Louis Park, Minnesota, United States, 55426

Contact: Wiktoria Patek Wiktoria.X.Pasek@HealthPartners.Com

Principal Investigator: Michael Schnaus, MD

Regions Hospital; Recruiting

Saint Paul, Minnesota, United States, 55101

Contact: Wiktoria Patek Wiktoria.X.Pasek@HealthPartners.Com

Principal Investigator: Charles Bruen, MD

United States, Missouri

University of Missouri School of Medicine; Recruiting

Columbia, Missouri, United States, 65212

Contact: Mihiri DeSilva desilvam@health.missouri.edu

Principal Investigator: Syed Naqvi, MD

Washington University School of Medicine; Completed

Saint Louis, Missouri, United States, 63110

United States, New York

Northshore University Hospital; Recruiting

Manhasset, New York, United States, 11030

Contact: Meghan Keating mkeating1@northwell.edu

Principal Investigator: Daniel Rolston, MD

Long Island Jewish Hospital; Withdrawn

New Hyde Park, New York, United States, 11040

Icahn School of Medicine at Mount Sinai; Recruiting

New York, New York, United States, 10029

Contact: Mitali Ashokkumar Pradhan, MS 201-423-3585 Mitali.Pradhan@mountsinai.org

Principal Investigator: Jonathan Schimmel, MD

United States, Ohio

Ohio State University; Recruiting

Columbus, Ohio, United States, 43201

Contact: Bryan Chu 614-668-6223 ChingMin.Chu@osumc.edu

Principal Investigator: Jason Bischof

United States, Tennessee

Regional One Health; Recruiting

Memphis, Tennessee, United States, 38106

Contact: Kimberly Barbee, BSN, RN kgbarbee@regionalonehealth.org

Principal Investigator: Amber Thacker, MD

United States, Texas

John Peter Smith Hospital; Recruiting

Fort Worth, Texas, United States, 76104

Contact: Lindsay Crutcher, RN, BSN 817-702-6746 LCrutche01@jpshealth.org

Contact: April Bell abell01@jpshealth.org

Principal Investigator: James D'Etienne, MD

Houston Methodist Hospital; Recruiting

Houston, Texas, United States, 77030

Contact: Anisha Gupte, PhD AAGUPTE@houstonmethodist.org

Principal Investigator: Raul Sanchez Leon, MD

UT Health Houston; Recruiting

Houston, Texas, United States, 77030

Contact: Neomi Sepulveda Neomi.Sepulveda@uth.tmc.edu

Principal Investigator: David Robinson, MD

University Health System at San Antonio; Withdrawn

San Antonio, Texas, United States, 78229

United States, Virginia

University of Virginia; Recruiting

Charlottesville, Virginia, United States, 22908

Contact: Ashley Simpson 434-924-2897 mailto:APS2H@hscmail.mcc.virginia.edu

Principal Investigator: Thomas Hartka, MD

Virginia Commonwealth University; Withdrawn

Richmond, Virginia, United States, 23298

United States, West Virginia

CAMC Institute for Academic Medicine; Recruiting

Charleston, West Virginia, United States, 25304

Contact: Katie Marberry, MSW 304-388-9957 morgan.marberry@camc.org

Principal Investigator: Harleen Chela, MD

Sponsors and Collaborators

CalciMedica, Inc.

Investigators

• Study Director: Sudarshan Hebbar, MD; CalciMedica, Inc.

More Information

• Responsible Party: CalciMedica, Inc.
• ClinicalTrials.gov Identifier: NCT04681066
• Other Study ID Numbers: CM4620-203
• First Posted: December 23, 2020
• Last Update Posted: June 7, 2023
• Last Verified: June 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pancreatitis; Syndrome; Systemic Inflammatory Response Syndrome; Disease; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Inflammation; Shock