A Study of Auxora in Patients With Critical COVID-19 Pneumonia

Study Overview
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Brief Summary
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This is a single-blind study consisting of up to 3 cohorts Patients will be randomized 3:1 to Auxora or Placebo. The first 4 patients will be enrolled in Cohort 1. If dose escalation occurs, the next 4 patients will be enrolled in Cohort 2 If dose escalation occurs, the next 8 patients will be enrolled in Cohort 3. The decision to escalate dosing will be made by CalciMedica in consultation with the PI and after the review of safety events in Cohorts 1 and 2.

Official Title
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A Single-Blind Dose-Ranging Pharmacodynamic Study of Auxora for the Treatment of Patients With Critical COVID-19 Pneumonia

Conditions
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Pneumonia

Intervention / Treatment
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* Drug: CM4620-IE (Injectable Emulsion)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay in any specimen; Moderate ARDS characterized by the following criteria: Invasive mechanical ventilation with a minimum PEEP of 5 cm H2O; PaO2/FiO2 ≤200 that may be estimated from pulse oximetry or determined by arterial blood gas; No evidence of volume overload or heart failure; The patient is ≥18 years of age at the time of consent; QTcF interval ≤ 440 milliseconds; A female patient of childbearing potential must not attempt to become pregnant for 39 months, and if sexually active with a male partner, is willing to practice acceptable methods of birth control for 39 months after the last dose of study drug; A male patient who is sexually active with a female partner of childbearing potential is willing to practice acceptable methods of birth control for 39 months after the last dose of study drug. A male patient must not donate sperm for 39 months; The patient is willing and able to, or has a legal authorized representative (LAR) who is willing and able to, provide informed consent to participate, and to cooperate with all aspects of the protocol. Exclusion Criteria: Expected survival or time to withdrawal of life-sustaining treatments expected to be <7 days. ECMO; Suspected septic shock; The patient has a history of: Organ or hematologic transplant; HIV; Active hepatitis B or hepatitis C infection; Current treatment with: Chemotherapy; Immunosuppressive medications or immunotherapy (see Section 5.3 for list of prohibited immunosuppressive medications and immunotherapy) at the time of consent; Hemodialysis or Peritoneal Dialysis; The patient is known to be pregnant or is nursing; Currently participating in another study of an investigational drug or therapeutic medical device at the time of consent; Allergy to eggs or any of the excipients in study drug.

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
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Auxora<br>Auxora will be given as a continuous infusion: Day 1: All 3 cohorts will receive 1.25 mL/kg over 4 hours; After initial infusion is complete, Cohort 3 will receive a continuous infusion of 1.0 mL/kg/24 hours for 96 hours Day 2: Cohort 1 will receive 1.0 mL/kg over 4 hours; Cohort 2 will receive 1.25mL/kg over 4 hours Day 3: Cohort 1 and 2 will receive 1.0 mL/kg over 4 hours Day 4: Cohort 2 will receive 1.0 mL/kg over 4 hours | Drug: CM4620-IE (Injectable Emulsion)<br>* Auxora is an injectable emulsion containing 1.6mg/ML of the active pharmaceutical ingredient CM4620. Auxora will be administered intravenously as a continuous infusion<br>* Other names: Auxora;|
| Placebo Comparator: Placebo<br>Placebo will be given as a continuous infusion: Day 1: All 3 cohorts will receive 1.25 mL/kg over 4 hours. After initial infusion is complete, Cohort 3 will receive a continuous infusion of 1.0 mL/kg/24 hours for 96 hours Day 2: Cohort 1 will receive 1.0 mL/kg over 4 hours; Cohort 2 will receive 1.25mL/kg over 4 hours Day 3: Cohort 1 and 2 will receive 1.0 mL/kg over 4 hours Day 4: Cohort 2 will receive 1.0 mL/kg over 4 hours | Drug: Placebo<br>* Matching placebo is an injectable emulsion containing no active pharmaceutical ingredient. Placebo will be administered intravenously as a continuous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of immune cells in BAL fluid and T cell activation will be assessed |  | Baseline Assessment up to 120 hours | 
| Impact of Auxora on the emergence of new clusters/cell types/cell states |  | Baseline Assessment up to 120 hours | 
| Impact of Auxora on detection of SARS-CoV-2 positive and negative strand RNA in infected cells |  | Baseline Assessment up to 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Levels of CM4620 | Concentration of Auxora from blood samples and fluid collected from BAL | From end of first infusion of study drug up to 144 hours | 
| Number of Days on Mechanical Ventilation after randomization |  | From randomization until patient is extubated assessed up to 60 days | 
| Number of Days in the Hospital after randomization |  | From randomization until discharge from the hospital assessed up to 60 days | 
| Number of Days in the Intensive Care Unit (ICU) after randomization |  | From randomization until discharge from ICU assessed up to 60 days | 
| Pre-defined changes in cardiac conduction assessed by ECG | Changes in cardiac conduction are defined as: QTcF interval of ≥ 500 msec; QTcF prolongation of ≥ 60 msec as compared to baseline; Mobitz Type II second degree atrioventricular (AV) block; Third degree or high grade AV block; or Polymorphic Ventricular Tachycardia | From screening up to 144 hours | 
| Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |  | From randomization up to 60 days | 
| Intensity and relationship of TEAEs and SAEs |  | From randomization up to 60 days | 
| Mortality |  | Randomization up to 60 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Coronavirus, Pneumonia, Calcium Release-Activated Calcium Channel (CRAC) Inhibitors, CM4620, Auxora