Acute Pancreatitis
Conditions
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.
Interventions
DRUGCM4620-IE
single IV infusion on Day 1 over 4 hours
Sponsors
CalciMedica, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 (Plasma Concentration of CM4620): Day 10 or Discharge | Day 10, or day of discharge | — |
| Pharmacokinetics (Plasma Concentration of CM4620): Day 30 | Day 30 | — |
| 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. |
| 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. |
| Baseline Levels of IL-6 | Baseline | Included plasma samples collected 1 hour prior to the study drug administration |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Patients CM4620-IE: single IV infusion on Day 1 over 4 hours | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Continuous | 42 years STANDARD_DEVIATION 8.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 3 / 7 |
| serious Total, serious adverse events | 1 / 7 |
Outcome results
Primary
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.
Time frame: Predose to 30 minutes post dose
Population: The final analysis set consisted of pre-dose to Discharge samples for 4 patients, due to logistical issues in timely assaying of the samples.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients | Exploratory: Percentage Change in IL-2 Production Relative to Pre-dose Values | -55.5 percentage of change in IL-2 production | Standard Error 5.8 |
Secondary
Baseline Levels of IL-6
Included plasma samples collected 1 hour prior to the study drug administration
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients | Baseline Levels of IL-6 | 46.04 pg/mL | Standard Error 26.3 |
Secondary
Day 1: 30 Minutes Post-infusion IL-6 Levels
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients | Day 1: 30 Minutes Post-infusion IL-6 Levels | 40.83 pg/mL | Standard Error 23.29 |
Secondary
Day 2: 20-hr Post Infusion IL-6 Levels
Time frame: Day 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients | Day 2: 20-hr Post Infusion IL-6 Levels | 24.8 pg/mL | Standard Error 12.4 |
Secondary
Pharmacokinetics (CMax of CM4620): Day 1, 30 Minutes Post End-of-infusion
Time frame: Days 1, 2, 5, 10 and 30 or at discharge if earlier than day 30
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Patients | Pharmacokinetics (CMax of CM4620): Day 1, 30 Minutes Post End-of-infusion | 791 Nanograms/mL | Geometric Coefficient of Variation 47 |
Secondary
Pharmacokinetics (Plasma Concentration of CM4620): Day 10 or Discharge
Time frame: Day 10, or day of discharge
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Patients | Pharmacokinetics (Plasma Concentration of CM4620): Day 10 or Discharge | 76 Ng/mL | Geometric Coefficient of Variation 46 |
Secondary
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.
Time frame: Day 2
Population: Samples were only received for analysis for 5 patients for day 2
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Patients | Pharmacokinetics (Plasma Concentration of CM4620): Day 2, 20-hr Post End-of-infusion | 109 Ng/mL | Geometric Coefficient of Variation 49 |
Secondary
Pharmacokinetics (Plasma Concentration of CM4620): Day 30
Time frame: Day 30
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| All Patients | Pharmacokinetics (Plasma Concentration of CM4620): Day 30 | 56 Ng/mL | Geometric Coefficient of Variation 32 |
Secondary
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.
Time frame: Assessed at Discharge, between 2 and 9 days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Patients | Post-infusion IL-6 Levels at Discharge | 13.9 pg/mL | Standard Error 2 |
Secondary
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.
Time frame: From baseline through 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Patients | The Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | 3 Participants |