A PK/PD Study of CM4620-IE in Patients With Acute Pancreatitis

A Pharmacodynamic and Pharmacokinetic Study of CM4620 Injectable Emulsion (CM4620-IE) in Patients With Acute Pancreatitis

This open-label study will evaluate the pharmacodynamic and pharmacokinetic profile of CM4620-IE in patients with acute pancreatitis. The first five (5) patients will receive ≤ 2.08 mg/kg of CM4620-IE by continuous IV infusion on Day 1. If necessary, up to an additional 4 patients may be treated at a different dose of CM4620-IE as determined by the obtained PK and PD data. The infusion of CM4620-IE will start within 12 hours from the time the patient or LAR provides informed consent.

Study Overview

• Status: Completed
• Conditions: Acute Pancreatitis
• Intervention / Treatment: Drug: CM4620-IE

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of acute pancreatitis established by the presence of abdominal pain consistent with acute pancreatitis, and 1 of the following 2 criteria:

   1. Serum lipase and/or serum amylase > 3 times the upper limit of normal (ULN);
   2. Characteristic findings of acute pancreatitis on abdominal imaging;
2. Adults ≥ 18 years of age;
3. A female patient of child-bearing potential who is sexually active with a male partner must be willing to practice acceptable methods of birth control for 365 days after the last dose of CM4620-IE;
4. A male patient who is sexually active with a female partner of childbearing potential must be willing to practice acceptable methods of birth control for 365 days after the last dose of CM4620-IE and must not donate sperm for 365 days;
5. Willing and able to, or have a legal authorized representative (LAR) who is willing and able to, provide informed consent to participate, and cooperate with all aspects of the protocol.

Exclusion Criteria:

1. Any concurrent clinical condition that a study physician believes could potentially pose an unacceptable health risk to the patient while involved in the study or may limit expected survival to < 6 months;
2. Suspected presence of cholangitis in the judgment of the treating investigator;
3. Any malignancy being treated with chemotherapy or immunotherapy;
4. Any autoimmune disease being treated with immunosuppressive medication or immunotherapy (Section 5.3 for list of prohibited medications);

5. History of:

   1. Chronic pancreatitis, pancreatic necrosectomy, or pancreatic enzyme replacement therapy;
   2. Biopsy proven cirrhosis, portal hypertension, hepatic failure/hepatic encephalopathy;
   3. Known hepatitis B or C, or HIV;
   4. History of organ or hematologic transplant;
   5. Myocardial infarction, revascularization, cardiovascular accident (CVA) in the 30 days prior to Day 1;
6. Current renal replacement therapy;
7. Current known abuse of cocaine or methamphetamine;
8. Known to be pregnant or are nursing;
9. Participated in another study of an investigational drug or therapeutic medical device in the 30 days prior to Day 1;
10. History of allergy to eggs or known hypersensitivity to any components of CM4620-IE;
11. Prior treatment with CM4620-IE.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: All Patients	Drug: CM4620-IE; single IV infusion on Day 1 over 4 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory: Percentage Change in IL-2 Production Relative to Pre-dose Values	Outcome assessed the percent change in IL-2 production after the administration of a single dose of CM4620-IE as compared to baseline production, for all patients enrolled. This measurement was to explore if there was a change in IL-2 levels with acute pancreatitis after the administration of a single dose of CM4620-IE.	Predose to 30 minutes post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The number of participants who experienced treatment-emergent adverse events (TEAEs) with Investigator-specified relationship to CM4620-IE and assessment of severity.	From baseline through 30 days
Pharmacokinetics (CMax of CM4620): Day 1, 30 Minutes Post End-of-infusion		Days 1, 2, 5, 10 and 30 or at discharge if earlier than day 30
Pharmacokinetics (Plasma Concentration of CM4620): Day 2, 20-hr Post End-of-infusion	Time points for sampling of plasma for bioanalysis of CM4620, blood for PD analysis (stimulated IL-2 release), and serum for cytokine analysis were chosen to capture the expected maximal plasma concentration (Cmax) on Day 1 and times close to the minimum plasma concentration (Cmin) on subsequent days.	Day 2
Pharmacokinetics (Plasma Concentration of CM4620): Day 10 or Discharge		Day 10, or day of discharge
Pharmacokinetics (Plasma Concentration of CM4620): Day 30		Day 30
Baseline Levels of IL-6	Included plasma samples collected 1 hour prior to the study drug administration	Baseline
Day 1: 30 Minutes Post-infusion IL-6 Levels		Day 1
Day 2: 20-hr Post Infusion IL-6 Levels		Day 2
Post-infusion IL-6 Levels at Discharge	This sample was drawn immediately prior to discharge from hospitalization, and ranged from day 2 through day 9.	Assessed at Discharge, between 2 and 9 days.

Collaborators and Investigators

• Sponsor: CalciMedica, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 6, 2019
• Primary Completion (ACTUAL): March 7, 2019
• Study Completion (ACTUAL): June 7, 2019

Study Registration Dates

• First Submitted: October 11, 2018
• First Submitted That Met QC Criteria: October 12, 2018
• First Posted (ACTUAL): October 17, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 3, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pancreatic Diseases; Pancreatitis
• Other Study ID Numbers: CM4620-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No