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

NCT04345614 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CM4620-204
• Study Type: interventional
• Target: 314
• Locations: 1 country
• Sites: 17

Brief Summary

Part 1 of this trial enrolled 30 patients to receive Auxora (formerly CM4620) in a 2:1 randomized, open label trial of patients with severe and critical COVID-19 pneumonia. Part 2 of this study randomized 284 patients and was a randomized, double blind, placebo-controlled (RCT) study that evaluated the efficacy, safety, and the pharmacokinetic profile of Auxora in patients with severe COVID-19 pneumonia. The number of patients with an imputed PaO2/FiO2 \>200 randomized into the study was capped at 26. Another 258 patients with a PaO2/FiO2 ≤200 were enrolled. Patients with an estimated PaO2/FiO2 of 75-200 were stratified to ensure balanced randomization between the Auxora and placebo arms. Subgroup analyses were performed to explore how time to recovery is influenced by baseline variables and to evaluate the treatment effect at different levels of each of these variables. The dose of Auxora was 2.0 mg/kg (1.25 mL/kg) administered at 0 hour, and then 1.6 mg/kg (1 mL/kg) at 24 hours and 1.6 mg/kg (1 mL/kg) at 48 hours from the SFISD. The dose of placebo was 1.25 mL/kg administered at 0 hour and then 1 mL/kg at 24 hours and 1 mL/kg at 48 hours from the SFISD. Remdesivir, corticosteroids and convalescent plasma were allowed. The infusion of Auxora / Placebo started within 12 hours from the time the patient or LAR provided informed consent. Efficacy analyses will be presented by treatment group (Auxora vs Placebo) based on the Efficacy Analysis Set of the imputed PaO2/FiO2 ≤200 subgroup, except where it is specified otherwise. The statistical analysis approach was designed to assess the significance of the primary and first secondary endpoint using the Benjamini and Hochberg method to control the overall trial level alpha level.

Conditions

Pneumonia

Keywords

COVID-19; Coronavirus; Pneumonia; Calcium release-activated calcium channel (CRAC) inhibitors; CM4620; Auxora

Outcome Measures

Primary Outcomes (1)

• Number of Days From the Start of the First Infusion of Study Drug (SFISD) to Recovery

  Defined as the number of days hospitalized but not requiring supplemental oxygen or ongoing medical care, or; discharged and requiring supplemental oxygen, or; discharged, not requiring supplemental oxygen.

  From start of first infusion of study drug to day 60

Secondary Outcomes (15)

• Number of Participants Who Have Died at Day 30 (Mortality)

  Day 30

• Number of Participants Who Have Died at Day 60 (Mortality)

  Day 60

• Number of Participants Requiring Invasive Mechanical Ventilation or Dying (Part 1)

  From start of first infusion of study drug and up to Day 28

• Proportion of Patients Requiring Invasive Mechanical Ventilation or Dying (Part 2)

  from start of first infusion of study drug and up to day day 60

• Proportion of Patients Requiring Invasive Mechanical Ventilation (Part 2)

  from start of first infusion of study drug and up to day Day 60

Study Arms (4)

Auxora (Part 1)

EXPERIMENTAL

Patients were randomized 1:1 to receive either Auxora or standard of care

Drug: Auxora (Part 1)

Standard of Care (Part 1)

OTHER

Patients were randomized 1:1 to receive either Auxora or standard of care

Drug: Standard of Care (Part 1)

Auxora (Part 2)

EXPERIMENTAL

Patients were randomized 1:1 to receive Auxora or Placebo

Drug: Auxora (Part 2)

Placebo (Part 2)

PLACEBO COMPARATOR

Patients were randomized 1:1 to receive Auxora or Placebo

Drug: Placebo (Part 2)

Interventions

Auxora (Part 1) DRUG

Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.

Also known as: CM4620-Injectable Emulsion (IE)

Auxora (Part 1)

Standard of Care (Part 1) DRUG

Patients received standard of care

Also known as: Placebo-Injectable Emulsion

Standard of Care (Part 1)

Auxora (Part 2) DRUG

Auxora will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Auxora will be administered intravenously (IV) over 4 hours.

Also known as: CM4620-Injectable Emulsion (IE)

Auxora (Part 2)

Placebo (Part 2) DRUG

Placebo will be given at 2.0 mg/kg (1.25 mL/kg) on Day 1 and then 1.6 mg/kg (1.0 mL/kg) on Days 2 and 3. All doses of Placebo will be administered intravenously (IV) over 4 hours.

Also known as: Placebo-Injectable Emulsion

Placebo (Part 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. The diagnosis of COVID-19 established standard RT-PCR assay;
• At least 1 of the following symptoms:
• Fever, cough, sore throat, malaise, headache, muscle pain, dyspnea at rest or with exertion, confusion, or respiratory distress;
• At least 1 of the following clinical signs:
• Respiratory rate ≥30, heart rate ≥125, SpO2 \<93% on room air or requires \>2L oxygen by nasal cannula to maintain SpO2 ≥93%, or PaO2/FiO2 \<300, estimated from pulse oximetry or determined by arterial blood gas;
• The presence of a respiratory infiltrate or abnormality consistent with pneumonia that is documented by either a CXR or CT scan of the lungs;
• The patient is ≥18 years of age;
• 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 CM4620-IE;
• 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 CM4620-IE. 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.

You may not qualify if:

• Expected survival or time to withdrawal of life-sustaining treatments expected to be \<7 days.
• Do Not Intubate order;
• Home mechanical ventilation (noninvasive ventilation or via tracheotomy) except for continuous positive airway pressure or bi-level positive airway pressure (CPAP/BIPAP) used solely for sleep-disordered breathing;
• PaO2/FiO2 ≤75 at the time of Screening. The PaO2/FiO2 may be estimated from pulse oximetry (Appendix 1) or determined by arterial blood gas;
• Noninvasive positive pressure ventilation;
• Invasive mechanical ventilation via endotracheal intubation or tracheostomy;
• ECMO;
• Shock defined by the use of vasopressors;
• Multiple organ dysfunction or failure;
• Positive Influenza A or B testing if tested as local standard of care;
• The patient has a history any of the following: Organ or hematologic transplant;HIV; Active hepatitis B, or hepatitis C infection;
• Current treatment with:Chemotherapy; Immunosuppressive medications or immunotherapy at the time of consent; Hemodialysis or Peritoneal Dialysis
• Have a history of venous thromboembolism (VTE) (deep vein thrombosis \[DVT\] or pulmonary embolism \[PE\]) within 12 weeks prior to screening or have a history of recurrent (\> 1) VTE;
• 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;

Sponsors & Collaborators

• CalciMedica, Inc.: lead

Study Sites (17)

Long Beach Memorial

Long Beach, California, 90806, United States

Location

University of Southern California / LA County

Los Angeles, California, 90033, United States

Location

Sharp Memorial San Diego

San Diego, California, 92123, United States

Location

National Jewish Health / St. Joseph's Hospital

Denver, Colorado, 80220, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Baton Rouge General

Baton Rouge, Louisiana, 70809, United States

Location

Maine Medical Center

Portland, Maine, 04102, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Sinai Grace

Detroit, Michigan, 48235, United States

Location

Methodist Hospital

Saint Louis Park, Minnesota, 55426, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101, United States

Location

Texas Tech University Medical Center

El Paso, Texas, 79905, United States

Location

John Peter Smith Hospital

Fort Worth, Texas, 76104, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Aurora Baycare

Green Bay, Wisconsin, 54311, United States

Location

Related Publications (2)

• Bruen C, Al-Saadi M, Michelson EA, Tanios M, Mendoza-Ayala R, Miller J, Zhang J, Stauderman K, Hebbar S, Hou PC. Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: a randomized-controlled clinical trial. Crit Care. 2022 Apr 8;26(1):101. doi: 10.1186/s13054-022-03964-8.

  PMID: 35395943 DERIVED

• Miller J, Bruen C, Schnaus M, Zhang J, Ali S, Lind A, Stoecker Z, Stauderman K, Hebbar S. Auxora versus standard of care for the treatment of severe or critical COVID-19 pneumonia: results from a randomized controlled trial. Crit Care. 2020 Aug 14;24(1):502. doi: 10.1186/s13054-020-03220-x.

  PMID: 32795330 DERIVED

Related Links

• Auxora vs. SOC for the treatment of severe COVID-19 pneumonia: a Phase 2 study (Part 1, open label)
• Auxora vs. placebo for the treatment of severe COVID-19 pneumonia: a Phase 2 study (Part 2, double-blinded)

MeSH Terms

Conditions

Pneumonia; COVID-19; Coronavirus Infections

Interventions

zegocractin; Standard of Care

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

The number of patients who participated in the biomarker collection was not sufficient to provide / record meaningful results.

Results Point of Contact

• Title: Sudarshan Hebbar, MD
• Organization: CalciMedica, Inc.

sudarshan@calcimedica.com

8168387105

Study Officials

• Sudarshan Hebbar, MD

  CalciMedica, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Matching placebo
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2020
• First Posted: April 14, 2020
• Study Start: April 8, 2020
• Primary Completion: June 28, 2021
• Study Completion: July 30, 2021
• Last Updated: March 30, 2026
• Results First Posted: August 20, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)