Pneumonia
Conditions
Keywords
COVID-19, Coronavirus, Pneumonia, Calcium release-activated calcium channel (CRAC) inhibitors, CM4620, Auxora
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.
Interventions
DRUGAuxora (Part 1)
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.
DRUGStandard of Care (Part 1)
Patients received standard of care
DRUGAuxora (Part 2)
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.
DRUGPlacebo (Part 2)
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.
Sponsors
CalciMedica, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Matching placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part 1: Inclusion Criteria 1. 1\. The diagnosis of COVID-19 established standard RT-PCR assay; 2. 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; 3. 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; 4. The presence of a respiratory infiltrate or abnormality consistent with pneumonia that is documented by either a CXR or CT scan of the lungs; 5. The patient is ≥18 years of age; 6. 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; 7. 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; 8. 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. Do Not Intubate order; 3. 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; 4. 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; 5. Noninvasive positive pressure ventilation; 6. Invasive mechanical ventilation via endotracheal intubation or tracheostomy; 7. ECMO; 8. Shock defined by the use of vasopressors; 9. Multiple organ dysfunction or failure; 10. Positive Influenza A or B testing if tested as local standard of care; 11. The patient has a history any of the following: Organ or hematologic transplant;HIV; Active hepatitis B, or hepatitis C infection; 12. Current treatment with:Chemotherapy; Immunosuppressive medications or immunotherapy at the time of consent; Hemodialysis or Peritoneal Dialysis 13. 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; 14. The patient is known to be pregnant or is nursing; 15. Currently participating in another study of an investigational drug or therapeutic medical device at the time of consent; 16. Allergy to eggs or any of the excipients in study drug. Part 2: 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, as documented by either of the following: * PCR positive in sample collected \< 72 hours prior to randomization; * PCR positive in sample collected ≥ 72 hours prior to randomization, with inability to obtain a repeat sample (e.g. due to lack of testing supplies, or limited testing capacity, or results taking \>24 hours, etc.) or progressive disease suggestive of ongoing SARS-CoV-2 infection; 2. 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; 3. At least 1 of the following signs at Screening or noted in the 24 hours before Screening: * PaO2/FiO2 ≤200 when receiving supplemental oxygen. The PaO2/FiO2 may be estimated from pulse oximetry (Appendix 1) or determined by arterial blood gas; * If SpO2 ≥97%, must be receiving 10L or more of supplemental oxygen; 4. The presence of a respiratory infiltrate or abnormality consistent with pneumonia that is documented by either a chest X-ray or computerized tomography scan of the lungs; 5. The patient is ≥ 18 years of age; 6. 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; 7. 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; 8. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days From the Start of the First Infusion of Study Drug (SFISD) to Recovery | From start of first infusion of study drug to day 60 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Improvement in 8-point Ordinal Scale (Part 1) | from start of first infusion of study drug and up to day 28 | The ordinal scale is an assessment of the clinical status in a given day. The scale is as follows: 1. Death 2. Hospitalized, requiring invasive mechanical ventilation or ECMO 3. Hospitalized, requiring non-invasive ventilation or high flow supplemental oxygen 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen or ongoing medical care 7. discharged, requiring supplemental oxygen 8. Discharged, not requiring supplemental oxygen |
| Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | from start of first infusion of study drug hrough Day 60 | The ordinal scale is an assessment of the clinical status in a given day. The scale is as follows: 1. Death 2. Hospitalized, requiring invasive mechanical ventilation or ECMO 3. Hospitalized, requiring non-invasive ventilation or high flow supplemental oxygen 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen or ongoing medical care 7. discharged, requiring supplemental oxygen 8. Discharged, not requiring supplemental oxygen |
| Change in PaO2/FiO2 (Part 1) | From start of first infusion of study drug through Day 28 | Measures of PaO2/FiO2 ratio |
| Number of Days in the Hospital(Part 1) | From start of first infusion of study drug through Discharge up to 28 days | Time to discharge alive from hospital |
| Number of Days in the Hospital (Part 2) | from admission into the hospital until discharge from the hospital up to 60 days | — |
| Number of Days in the Intensive Care Unit (ICU) (Part 2) | from admission into ICU until discharge from ICU up to 60 days | — |
| Days Alive and Free of Mechanical Ventilation (Part 1) | From randomization through Day 28 | — |
| Number of Participants Considered Recovered (Part 1) | From start of first infusion of study drug through Day 28 | Recovery is defined as a 6, 7, or 8 on the 8 point ordinal scale |
| CM4620-IE Plasma Concentration (Part 2) | From start of first infusion of study drug through 72 hours | Concentration measured using a validated assay |
| Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | From start of first infusion of study drugand through day 60 | — |
Countries
United States
Contacts
STUDY_DIRECTORSudarshan Hebbar, MD
CalciMedica, Inc.
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Auxora (Part 1) Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care.
The dose of CM4620-IE was 2.0 mg/kg of CM4620-IE administered at 0 hour, and 1.6 mg/kg at 24 hours and 1.6 mg/kg at 48 hours | 17 |
| Standard of Care (Part 1) Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. | 9 |
| Auxora (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo
Auxora: Auxora was 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. | 130 |
| Placebo (Part 2) Patients were randomized 1:1 to receive either Auxora or placebo
Placebo: Placebo was given at 1.25 mL/kg on Day 1 and then 1.0 mL/kg on Days 2 and 3. All doses of placebo will be administered intravenously over 4 hours. | 131 |
| Total | 287 |
Baseline characteristics
| Characteristic | Auxora (Part 1) | Standard of Care (Part 1) | Auxora (Part 2) | Placebo (Part 2) | Total |
|---|---|---|---|---|---|
| 65+years of age | 4 Participants | 4 Participants | 45 Participants | 47 Participants | 100 Participants |
| Age, Continuous | 59.3 years STANDARD_DEVIATION 12.47 | 61.0 years STANDARD_DEVIATION 13.32 | 59.4 years STANDARD_DEVIATION 12.1 | 60.4 years STANDARD_DEVIATION 12.3 | 59.9 years STANDARD_DEVIATION 12.2 |
| Baseline imputed PaO2/FiO2=/<100 | 4 Participants | 2 Participants | 59 Participants | 58 Participants | 123 Participants |
| Baseline imputed PaO2/FiO2 101-200 | 6 Participants | 4 Participants | 71 Participants | 73 Participants | 154 Participants |
| Baseline imputed PaO2/FiO2 value | 177.5 Ratio STANDARD_DEVIATION 74.03 | 167.6 Ratio STANDARD_DEVIATION 77.6 | 109.7 Ratio STANDARD_DEVIATION 36.8 | 105.1 Ratio STANDARD_DEVIATION 32.8 | 107.4 Ratio STANDARD_DEVIATION 34.8 |
| Body Mass Index | 34.4 kg/m^2 STANDARD_DEVIATION 13.5 | 33.1 kg/m^2 STANDARD_DEVIATION 8.58 | 32.8 kg/m^2 STANDARD_DEVIATION 8.8 | 32.0 kg/m^2 STANDARD_DEVIATION 7 | 32.4 kg/m^2 STANDARD_DEVIATION 8 |
| C-reactive protein (CRP) | 99.9 mg/L STANDARD_DEVIATION 68.34 | 124.3 mg/L STANDARD_DEVIATION 59.28 | 93.1 mg/L STANDARD_DEVIATION 71.2 | 92.5 mg/L STANDARD_DEVIATION 67.6 | 92.8 mg/L STANDARD_DEVIATION 69.2 |
| Diabetes | 8 Participants | 2 Participants | 52 Participants | 57 Participants | 119 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 45 Participants | 58 Participants | 106 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 6 Participants | 82 Participants | 72 Participants | 174 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants | 1 Participants | 7 Participants |
| Ferritin | 709.1 ng/mL STANDARD_DEVIATION 553.09 | 771.6 ng/mL STANDARD_DEVIATION 741.57 | 1027 ng/mL STANDARD_DEVIATION 907 | 1050 ng/mL STANDARD_DEVIATION 869 | 1039 ng/mL STANDARD_DEVIATION 886 |
| Former smoker | 5 Participants | 2 Participants | 39 Participants | 34 Participants | 80 Participants |
| High-flow nasal cannula use (HFNC) | 0 Participants | 0 Participants | 81 Participants | 82 Participants | 163 Participants |
| Hyperlipidemia | 2 Participants | 0 Participants | 50 Participants | 51 Participants | 103 Participants |
| Hypertension | 8 Participants | 4 Participants | 84 Participants | 80 Participants | 176 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 9 Participants | 5 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 3 Participants | 19 Participants | 12 Participants | 41 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 16 Participants | 15 Participants | 33 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 5 Participants | 85 Participants | 98 Participants | 196 Participants |
| Region of Enrollment United States | 17 participants | 9 participants | 130 participants | 131 participants | 287 participants |
| Sex: Female, Male Female | 10 Participants | 4 Participants | 46 Participants | 39 Participants | 99 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 84 Participants | 92 Participants | 188 Participants |
| Time from symptom onset | 11.1 Days STANDARD_DEVIATION 7.13 | 6.9 Days STANDARD_DEVIATION 2.59 | 12.2 Days STANDARD_DEVIATION 5.8 | 12.0 Days STANDARD_DEVIATION 5.9 | 12.1 Days STANDARD_DEVIATION 5.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 20 | 2 / 10 | 18 / 141 | 27 / 140 |
| other Total, other adverse events | 15 / 20 | 8 / 10 | 69 / 141 | 68 / 140 |
| serious Total, serious adverse events | 6 / 20 | 5 / 10 | 34 / 141 | 49 / 140 |
Outcome results
Primary
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.
Time frame: From start of first infusion of study drug to day 60
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Auxora (Part 1) | Number of Days From the Start of the First Infusion of Study Drug (SFISD) to Recovery | 5 Days |
| Standard of Care (Part 1) | Number of Days From the Start of the First Infusion of Study Drug (SFISD) to Recovery | 12 Days |
| Auxora (Part 2) | Number of Days From the Start of the First Infusion of Study Drug (SFISD) to Recovery | 7.0 Days |
| Placebo (Part 2) | Number of Days From the Start of the First Infusion of Study Drug (SFISD) to Recovery | 10.0 Days |
Secondary
Change in PaO2/FiO2 (Part 1)
Measures of PaO2/FiO2 ratio
Time frame: From start of first infusion of study drug through Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Auxora (Part 1) | Change in PaO2/FiO2 (Part 1) | 66.94 ratio of the arterial partial pressure o | Standard Deviation 152.673 |
| Standard of Care (Part 1) | Change in PaO2/FiO2 (Part 1) | 153.31 ratio of the arterial partial pressure o | Standard Deviation 153.258 |
Secondary
CM4620-IE Plasma Concentration (Part 2)
Concentration measured using a validated assay
Time frame: From start of first infusion of study drug through 72 hours
Population: Patients with a viable PK sample at 72 hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Auxora (Part 1) | CM4620-IE Plasma Concentration (Part 2) | 165.2 ng/mL | Standard Deviation 91.9 |
Secondary
Days Alive and Free of Mechanical Ventilation (Part 1)
Time frame: From randomization through Day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Auxora (Part 1) | Days Alive and Free of Mechanical Ventilation (Part 1) | 22.9 Days | Standard Deviation 10.3 |
| Standard of Care (Part 1) | Days Alive and Free of Mechanical Ventilation (Part 1) | 12.9 Days | Standard Deviation 14.3 |
Secondary
Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2)
The ordinal scale is an assessment of the clinical status in a given day. The scale is as follows: 1. Death 2. Hospitalized, requiring invasive mechanical ventilation or ECMO 3. Hospitalized, requiring non-invasive ventilation or high flow supplemental oxygen 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen or ongoing medical care 7. discharged, requiring supplemental oxygen 8. Discharged, not requiring supplemental oxygen
Time frame: from start of first infusion of study drug hrough Day 60
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Auxora (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 3 | 81 Participants |
| Auxora (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 2 | 0 Participants |
| Auxora (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 1 | 0 Participants |
| Auxora (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 4 | 49 Participants |
| Auxora (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 5 | 0 Participants |
| Auxora (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 6 | 0 Participants |
| Auxora (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 7 | 0 Participants |
| Auxora (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 8 | 0 Participants |
| Standard of Care (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 5 | 0 Participants |
| Standard of Care (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 3 | 82 Participants |
| Standard of Care (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 6 | 0 Participants |
| Standard of Care (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 7 | 0 Participants |
| Standard of Care (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 1 | 0 Participants |
| Standard of Care (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 4 | 49 Participants |
| Standard of Care (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 2 | 0 Participants |
| Standard of Care (Part 1) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 8 | 0 Participants |
| Auxora (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 7 | 38 Participants |
| Auxora (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 5 | 0 Participants |
| Auxora (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 8 | 45 Participants |
| Auxora (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 3 | 17 Participants |
| Auxora (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 6 | 0 Participants |
| Auxora (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 4 | 6 Participants |
| Auxora (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 1 | 5 Participants |
| Auxora (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 2 | 11 Participants |
| Placebo (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 8 | 36 Participants |
| Placebo (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 2 | 23 Participants |
| Placebo (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 1 | 8 Participants |
| Placebo (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 4 | 7 Participants |
| Placebo (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 3 | 16 Participants |
| Placebo (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 5 | 0 Participants |
| Placebo (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 6 | 0 Participants |
| Placebo (Part 2) | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 7 | 39 Participants |
| Auxora Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 4 | 2 Participants |
| Auxora Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 7 | 24 Participants |
| Auxora Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 3 | 5 Participants |
| Auxora Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 1 | 10 Participants |
| Auxora Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 8 | 71 Participants |
| Auxora Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 5 | 0 Participants |
| Auxora Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 6 | 1 Participants |
| Auxora Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 2 | 11 Participants |
| Placebo Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 8 | 58 Participants |
| Placebo Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 2 | 8 Participants |
| Placebo Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 3 | 3 Participants |
| Placebo Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 1 | 23 Participants |
| Placebo Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 7 | 33 Participants |
| Placebo Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 6 | 2 Participants |
| Placebo Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 5 | 0 Participants |
| Placebo Day 30 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 4 | 2 Participants |
| Auxora Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 3 | 0 Participants |
| Auxora Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 2 | 3 Participants |
| Auxora Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 4 | 0 Participants |
| Auxora Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 5 | 0 Participants |
| Auxora Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 6 | 2 Participants |
| Auxora Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 8 | 69 Participants |
| Auxora Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 7 | 32 Participants |
| Auxora Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 1 | 18 Participants |
| Placebo Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 8 | 59 Participants |
| Placebo Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 6 | 5 Participants |
| Placebo Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 5 | 0 Participants |
| Placebo Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 4 | 0 Participants |
| Placebo Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 3 | 0 Participants |
| Placebo Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 2 | 5 Participants |
| Placebo Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 1 | 27 Participants |
| Placebo Day 60 | Differences in Outcomes as Measured by an 8-point Ordinal Scale (Part 2) | 7 | 33 Participants |
Secondary
Improvement in 8-point Ordinal Scale (Part 1)
The ordinal scale is an assessment of the clinical status in a given day. The scale is as follows: 1. Death 2. Hospitalized, requiring invasive mechanical ventilation or ECMO 3. Hospitalized, requiring non-invasive ventilation or high flow supplemental oxygen 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care 6. Hospitalized, not requiring supplemental oxygen or ongoing medical care 7. discharged, requiring supplemental oxygen 8. Discharged, not requiring supplemental oxygen
Time frame: from start of first infusion of study drug and up to day 28
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Auxora (Part 1) | Improvement in 8-point Ordinal Scale (Part 1) | 6.3 score on a scale | Standard Deviation 2.39 |
| Standard of Care (Part 1) | Improvement in 8-point Ordinal Scale (Part 1) | 4.6 score on a scale | Standard Deviation 2.92 |
Secondary
Number of Days in the Hospital(Part 1)
Time to discharge alive from hospital
Time frame: From start of first infusion of study drug through Discharge up to 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Auxora (Part 1) | Number of Days in the Hospital(Part 1) | 5 Days |
| Standard of Care (Part 1) | Number of Days in the Hospital(Part 1) | 12 Days |
Secondary
Number of Days in the Hospital (Part 2)
Time frame: from admission into the hospital until discharge from the hospital up to 60 days
Population: Number of days in the hospital during the first 28 days of the study with a baseline imputed PaO2/FiO2 \</= 200
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Auxora (Part 1) | Number of Days in the Hospital (Part 2) | 13.65 Days |
| Standard of Care (Part 1) | Number of Days in the Hospital (Part 2) | 15.29 Days |
Secondary
Number of Days in the Intensive Care Unit (ICU) (Part 2)
Time frame: from admission into ICU until discharge from ICU up to 60 days
Population: Number of ICU days during the first 28 days of the study in patients with a baseline imputed PaO2/FiO2 \</= 200
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Auxora (Part 1) | Number of Days in the Intensive Care Unit (ICU) (Part 2) | 6.88 Days |
| Standard of Care (Part 1) | Number of Days in the Intensive Care Unit (ICU) (Part 2) | 8.36 Days |
Secondary
Number of Participants Considered Recovered (Part 1)
Recovery is defined as a 6, 7, or 8 on the 8 point ordinal scale
Time frame: From start of first infusion of study drug through Day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Auxora (Part 1) | Number of Participants Considered Recovered (Part 1) | 14 Participants |
| Standard of Care (Part 1) | Number of Participants Considered Recovered (Part 1) | 4 Participants |
Secondary
Number of Participants Requiring Invasive Mechanical Ventilation or Dying (Part 1)
Time frame: From start of first infusion of study drug and up to Day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Auxora (Part 1) | Number of Participants Requiring Invasive Mechanical Ventilation or Dying (Part 1) | 4 Participants |
| Standard of Care (Part 1) | Number of Participants Requiring Invasive Mechanical Ventilation or Dying (Part 1) | 5 Participants |
Secondary
Number of Participants Who Have Died at Day 30 (Mortality)
Time frame: Day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Auxora (Part 1) | Number of Participants Who Have Died at Day 30 (Mortality) | 2 Participants |
| Standard of Care (Part 1) | Number of Participants Who Have Died at Day 30 (Mortality) | 2 Participants |
| Auxora (Part 2) | Number of Participants Who Have Died at Day 30 (Mortality) | 10 Participants |
| Placebo (Part 2) | Number of Participants Who Have Died at Day 30 (Mortality) | 23 Participants |
Secondary
Number of Participants Who Have Died at Day 60 (Mortality)
Time frame: Day 60
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Auxora (Part 1) | Number of Participants Who Have Died at Day 60 (Mortality) | 2 Participants |
| Standard of Care (Part 1) | Number of Participants Who Have Died at Day 60 (Mortality) | 2 Participants |
| Auxora (Part 2) | Number of Participants Who Have Died at Day 60 (Mortality) | 18 Participants |
| Placebo (Part 2) | Number of Participants Who Have Died at Day 60 (Mortality) | 27 Participants |
Secondary
Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
Time frame: From start of first infusion of study drugand through day 60
Population: For Part 1 of the study, all 30 treated patients were included in the Safety Analysis Set. In Part 2, 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Auxora (Part 1) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Severe TEAE | 25.0 percentage of patients |
| Auxora (Part 1) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Mild TEAE | 20.0 percentage of patients |
| Auxora (Part 1) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Patients with at least one treatment related TEAE | 15.0 percentage of patients |
| Auxora (Part 1) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Moderate TEAE | 25.0 percentage of patients |
| Auxora (Part 1) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Patients with at least 1 TEAE | 75.0 percentage of patients |
| Standard of Care (Part 1) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Moderate TEAE | 10.0 percentage of patients |
| Standard of Care (Part 1) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Severe TEAE | 10.0 percentage of patients |
| Standard of Care (Part 1) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Patients with at least one treatment related TEAE | 0.0 percentage of patients |
| Standard of Care (Part 1) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Mild TEAE | 20.0 percentage of patients |
| Standard of Care (Part 1) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Patients with at least 1 TEAE | 80.0 percentage of patients |
| Auxora (Part 2) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Moderate TEAE | 10.6 percentage of patients |
| Auxora (Part 2) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Patients with at least 1 TEAE | 64.5 percentage of patients |
| Auxora (Part 2) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Mild TEAE | 29.8 percentage of patients |
| Auxora (Part 2) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Severe TEAE | 24.1 percentage of patients |
| Auxora (Part 2) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Patients with at least one treatment related TEAE | 25.5 percentage of patients |
| Placebo (Part 2) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Severe TEAE | 35 percentage of patients |
| Placebo (Part 2) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Mild TEAE | 17.9 percentage of patients |
| Placebo (Part 2) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Patients with at least 1 TEAE | 61.4 percentage of patients |
| Placebo (Part 2) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Moderate TEAE | 8.6 percentage of patients |
| Placebo (Part 2) | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | Patients with at least one treatment related TEAE | 12.9 percentage of patients |
Secondary
Proportion of Patients Requiring Invasive Mechanical Ventilation or Dying (Part 2)
Time frame: from start of first infusion of study drug and up to day day 60
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Auxora (Part 1) | Proportion of Patients Requiring Invasive Mechanical Ventilation or Dying (Part 2) | .23 Proportion of Participants |
| Standard of Care (Part 1) | Proportion of Patients Requiring Invasive Mechanical Ventilation or Dying (Part 2) | .31 Proportion of Participants |
Secondary
Proportion of Patients Requiring Invasive Mechanical Ventilation (Part 2)
Time frame: from start of first infusion of study drug and up to day Day 60
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Auxora (Part 1) | Proportion of Patients Requiring Invasive Mechanical Ventilation (Part 2) | 0.19 Proportion of participants |
| Standard of Care (Part 1) | Proportion of Patients Requiring Invasive Mechanical Ventilation (Part 2) | 0.28 Proportion of participants |