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

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

This is a single-blind study of Auxora in patients with critical COVID-19 pneumonia, consisting of up to 3 cohorts of escalating dose. The main goal was to assess pharmacodynamic parameters of immune response, while also assessing safety and tolerability of the drug in this patient population.

Study Overview

• Status: Terminated
• Conditions: Pneumonia
• Intervention / Treatment: Drug: CM4620-IE (Injectable Emulsion); Drug: Placebo

Detailed Description

The primary objective of this study was to assess the pharmacodynamic response of bronchoalveolar lavage (BAL) T cell/monocyte subsets and chemokine release to various doses of Auxora in patients with critical COVID-19 pneumonia. Other objectives included assessment of safety and tolerability of Auxora in patients with critical COVID-19 pneumonia, as well as pharmacokinetic profile of Auxora in these patients. Efficacy was also to be examined based on all-cause mortality at day 60, number of days on mechanical ventilation after randomization, number of days in the hospital after randomization, and number of days in the ICU after randomization.

Patients were randomized 3:1 to Auxora or Placebo. The first 4 patients were enrolled in Cohort 1 (3 Auxora, 1 Placebo). If dose escalation occurred, the next 4 patients were to be enrolled in Cohort 2. If dose escalation occurred again, the next 8 patients were to be enrolled in Cohort 3. The decision to escalate dosing was made by CalciMedica in consultation with the PI and after the review of safety events in Cohorts 1 and 2.

(Note: Trial terminated early after the first patient was enrolled in Cohort 3 due to lack of new Covid-19 hospitalizations.)

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay in any specimen;

2. 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;
3. The patient is ≥18 years of age at the time of consent;
4. QTcF interval ≤ 440 milliseconds;
5. 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;
6. 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;
7. 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:

1. Expected survival or time to withdrawal of life-sustaining treatments expected to be <7 days.
2. ECMO;
3. Suspected septic shock;

4. The patient has a history of:

   • Organ or hematologic transplant;
   • HIV;
   • Active hepatitis B or hepatitis C infection;

5. 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;
6. The patient is known to be pregnant or is nursing;
7. Currently participating in another study of an investigational drug or therapeutic medical device at the time of consent;
8. Allergy to eggs or any of the excipients in study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Auxora; 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); Auxora is an injectable emulsion containing 1.6mg/ML of the active pharmaceutical ingredient CM4620. Auxora will be administered intravenously as a continuous infusion; Other Names: Auxora
Placebo Comparator: Placebo; 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; Matching placebo is an injectable emulsion containing no active pharmaceutical ingredient. Placebo will be administered intravenously as a continuous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Combined CD4, CD8, and Monocyte Cell Population in BAL Fluid, as a Percent of Total WBC Population.	Pharmacodynamic endpoint: Assessment of pharmacodynamic response of bronchoalveolar lavage (BAL) T cell/monocyte subsets to Auxora treatment. Flow cytometry was performed on fluid collected from the BAL performed prior to the SFISD (-12 hours) and 24 (±12) hours after completing the last infusion of study drug in Cohorts 1 and 2 and during the final 24 hours of the continuous infusion in Cohort 3. The percentage of total WBC population was assessed for the combined CD4, CD8, and monocyte cell population, and the change between Pre- and Post-Infusion samples (Post value minus Pre value) was reported.	Baseline Assessment up to 120 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Percent of Immune Cells in BAL Fluid	Pharmacodynamic endpoint: Assessment of pharmacodynamic response of bronchoalveolar lavage (BAL) T cell/monocyte subsets to Auxora treatment. Flow cytometry was performed on fluid collected from the BAL performed prior to the SFISD (-12 hours) and 24 (±12) hours after completing the last infusion of study drug in Cohorts 1 and 2 and during the final 24 hours of the continuous infusion in Cohort 3. The percentage of total WBC population was assessed for immune cell types and the change between Pre- and Post-Infusion samples (Post value minus Pre value) was reported.	Baseline Assessment up to 120 hours
Number of Patients Alive at Day 60	Efficacy endpoint: All-cause Mortality at Day 60	Randomization through Day 60
Number of Days Alive and Out of the Intensive Care Unit (ICU)	Efficacy Endpoint: Days in ICU (after randomization)	From randomization until discharge from ICU, assessed up to 60 days
Number of Days Alive and Out of the Hospital	Efficacy endpoint: Days hospitalized (after randomization)	From randomization until discharge from the hospital, assessed up to 60 days
Number of Days Alive and Off Mechanical Ventilation	Efficacy endpoint: Ventilator-free days (after randomization)	From randomization until patient is extubated, assessed up to 60 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Experiencing an AE Considered Possibly Related to Study Drug	Safety endpoint. Examines the relatedness of AEs to study drug by assessing the number of patients experiencing any AE (serious or non-serious) considered possibly related to Study Drug.	Randomization through Day 30
Number of Patients Experiencing an SAE (at Least 1)	Safety Endpoint: Incidence of treatment emergent Serious Adverse Events (SAEs)	Randomization through day 30
Intensity of AEs	Safety endpoint: Count of the number of AEs for each level of intensity: mild, moderate, or severe	Randomization through Day 30
Number of Patients Experiencing Pre-defined Changes in Cardiac Conduction Assessed by ECG	Safety endpoint: Patients experiencing Changes in cardiac conduction, 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 randomization up to 144 hours after SFISD (start of first infusion of study drug)

Collaborators and Investigators

• Sponsor: CalciMedica, Inc.
• Collaborators: Northwestern University

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2021
• Primary Completion (Actual): December 21, 2021
• Study Completion (Actual): December 21, 2021

Study Registration Dates

• First Submitted: December 4, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 10, 2020

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Pneumonia; Coronavirus; COVID-19; CM4620; Auxora; Calcium Release-Activated Calcium Channel (CRAC) Inhibitors
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Coronaviridae Infections; Nidovirales Infections; COVID-19; Pneumonia; Coronavirus Infections; zegocractin
• Other Study ID Numbers: CM4620-205

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No