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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All Patients | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CM4620-IE | Drug | single IV infusion on Day 1 over 4 hours |
|
| 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 |
| 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 |
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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:
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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Sudarshan Hebbar, MD | CalciMedica, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | All Patients | CM4620-IE: single IV infusion on Day 1 over 4 hours |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Patients | CM4620-IE: single IV infusion on Day 1 over 4 hours |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The final analysis set consisted of pre-dose to Discharge samples for 4 patients, due to logistical issues in timely assaying of the samples. | Posted | Mean | Standard Error | percentage of change in IL-2 production | Predose to 30 minutes post dose |
|
Adverse event data were collected over 90 days per subject, from the start of dosing until the 30-day follow-up.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Patients | CM4620-IE: single IV infusion on Day 1 over 4 hours | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Pancreatitis | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Melaena | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sudarshan Hebbar, MD | CalciMedica | 816-838-7105 | sudarshan@calcimedica.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 25, 2018 | May 10, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 29, 2019 | May 10, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D010195 | Pancreatitis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
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| 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. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| 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. | Posted | Count of Participants | Participants | From baseline through 30 days |
|
|
|
| Secondary | Pharmacokinetics (CMax of CM4620): Day 1, 30 Minutes Post End-of-infusion | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms/mL | Days 1, 2, 5, 10 and 30 or at discharge if earlier than day 30 |
|
|
|
| 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. | Samples were only received for analysis for 5 patients for day 2 | Posted | Geometric Mean | Geometric Coefficient of Variation | Ng/mL | Day 2 |
|
|
|
| Secondary | Pharmacokinetics (Plasma Concentration of CM4620): Day 10 or Discharge | Posted | Geometric Mean | Geometric Coefficient of Variation | Ng/mL | Day 10, or day of discharge |
|
|
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| Secondary | Pharmacokinetics (Plasma Concentration of CM4620): Day 30 | Posted | Geometric Mean | Geometric Coefficient of Variation | Ng/mL | Day 30 |
|
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|
| Secondary | Baseline Levels of IL-6 | Included plasma samples collected 1 hour prior to the study drug administration | Posted | Mean | Standard Error | pg/mL | Baseline |
|
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| Secondary | Day 1: 30 Minutes Post-infusion IL-6 Levels | Posted | Mean | Standard Error | pg/mL | Day 1 |
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| Secondary | Day 2: 20-hr Post Infusion IL-6 Levels | Posted | Mean | Standard Error | pg/mL | Day 2 |
|
|
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| 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. | Posted | Mean | Standard Error | pg/mL | Assessed at Discharge, between 2 and 9 days. |
|
|
|
| 7 |
| 1 |
| 7 |
| 3 |
| 7 |
| Respiratory Distress | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
|
| Bursitis | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
|
| Acute Pancreatitis | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment | This event is also captured as an SAE |
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| Pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA (10.0) | Systematic Assessment |
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| Alcohol Withdrawal Syndrome | General disorders | MedDRA (10.0) | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 21.1 | Systematic Assessment |
|
| Respiratory Distress | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment | This event is also captured as an SAE |
|
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