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

Phase 2

Completed

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

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;
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:
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;
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.

Arm && Interventions

Group	Intervention	Description
All Patients	CM4620-IE	-

Primary Outcome Measures

Name	Time	Method
Exploratory: Percentage Change in IL-2 Production Relative to Pre-dose Values	Predose to 30 minutes post dose	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.

Secondary Outcome Measures

Name	Time	Method
The Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	From baseline through 30 days	The number of participants who experienced treatment-emergent adverse events (TEAEs) with Investigator-specified relationship to CM4620-IE and assessment of severity.
Pharmacokinetics (Plasma Concentration of CM4620): Day 2, 20-hr Post End-of-infusion	Day 2	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.
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 30	Day 30
Baseline Levels of IL-6	Baseline	Included plasma samples collected 1 hour prior to the study drug administration
Pharmacokinetics (Plasma Concentration of CM4620): Day 10 or Discharge	Day 10, or day of discharge
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	Assessed at Discharge, between 2 and 9 days.	This sample was drawn immediately prior to discharge from hospitalization, and ranged from day 2 through day 9.