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

Study Overview
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Brief Summary
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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.

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

Conditions
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Acute Pancreatitis

Intervention / Treatment
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* Drug: CM4620-IE


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of acute pancreatitis established by the presence of abdominal pain consistent with acute pancreatitis, and 1 of the following 2 criteria: Serum lipase and/or serum amylase > 3 times the upper limit of normal (ULN); Characteristic findings of acute pancreatitis on abdominal imaging; Adults ≥ 18 years of age; 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; 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; 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: 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; Suspected presence of cholangitis in the judgment of the treating investigator; Any malignancy being treated with chemotherapy or immunotherapy; Any autoimmune disease being treated with immunosuppressive medication or immunotherapy (Section 5.3 for list of prohibited medications); History of: Chronic pancreatitis, pancreatic necrosectomy, or pancreatic enzyme replacement therapy; Biopsy proven cirrhosis, portal hypertension, hepatic failure/hepatic encephalopathy; Known hepatitis B or C, or HIV; History of organ or hematologic transplant; Myocardial infarction, revascularization, cardiovascular accident (CVA) in the 30 days prior to Day 1; Current renal replacement therapy; Current known abuse of cocaine or methamphetamine; Known to be pregnant or are nursing; Participated in another study of an investigational drug or therapeutic medical device in the 30 days prior to Day 1; History of allergy to eggs or known hypersensitivity to any components of CM4620-IE; Prior treatment with CM4620-IE.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Patients<br> | Drug: CM4620-IE<br>* single IV infusion on Day 1 over 4 hours<br>|

What is the study measuring?
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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. |