Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT04681066 |
| Other study ID # |
CM4620-203 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
March 24, 2021 |
| Est. completion date |
September 2024 |
Study information
| Verified date |
April 2024 |
| Source |
CalciMedica, Inc. |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
