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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Auxora (Part 1) | Experimental | Patients were randomized 1:1 to receive either Auxora or standard of care |
|
| Standard of Care (Part 1) | Other | Patients were randomized 1:1 to receive either Auxora or standard of care |
|
| Auxora (Part 2) | Experimental | Patients were randomized 1:1 to receive Auxora or Placebo |
|
| Placebo (Part 2) | Placebo Comparator | Patients were randomized 1:1 to receive Auxora or Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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Part 1:
Inclusion Criteria
1. 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.
Exclusion Criteria:
Part 2:
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, as documented by either of the following:
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 signs at Screening or noted in the 24 hours before Screening:
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;
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.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sudarshan Hebbar, MD | CalciMedica, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Long Beach Memorial | Long Beach | California | 90806 | United States | ||
| University of Southern California / LA County |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35395943 | Derived | 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. | |
| 32795330 | Derived |
| Label | URL |
|---|---|
| Auxora vs. SOC for the treatment of severe COVID-19 pneumonia: a Phase 2 study (Part 1, open label) | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | Standard of Care (Part 1) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Mar 31, 2021 | Jul 25, 2022 |
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Matching placebo
|
| Standard of Care (Part 1) | Drug | Patients received standard of care |
|
|
| 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. |
|
|
| 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. |
|
|
| 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) | 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 | from start of first infusion of study drug and up to day 28 |
| 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 | from start of first infusion of study drug hrough Day 60 |
| Change in PaO2/FiO2 (Part 1) | Measures of PaO2/FiO2 ratio | From start of first infusion of study drug through Day 28 |
| Number of Days in the Hospital(Part 1) | Time to discharge alive from hospital | From start of first infusion of study drug through Discharge up to 28 days |
| 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) | Recovery is defined as a 6, 7, or 8 on the 8 point ordinal scale | From start of first infusion of study drug through Day 28 |
| CM4620-IE Plasma Concentration (Part 2) | Concentration measured using a validated assay | From start of first infusion of study drug through 72 hours |
| 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 |
| Los Angeles |
| California |
| 90033 |
| United States |
| Sharp Memorial San Diego | San Diego | California | 92123 | United States |
| National Jewish Health / St. Joseph's Hospital | Denver | Colorado | 80220 | United States |
| Northwestern University | Chicago | Illinois | 60611 | United States |
| Baton Rouge General | Baton Rouge | Louisiana | 70809 | United States |
| Maine Medical Center | Portland | Maine | 04102 | United States |
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| Sinai Grace | Detroit | Michigan | 48235 | United States |
| Methodist Hospital | Saint Louis Park | Minnesota | 55426 | United States |
| Regions Hospital | Saint Paul | Minnesota | 55101 | United States |
| Texas Tech University Medical Center | El Paso | Texas | 79905 | United States |
| John Peter Smith Hospital | Fort Worth | Texas | 76104 | United States |
| Houston Methodist Hospital | Houston | Texas | 77030 | United States |
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
| Aurora Baycare | Green Bay | Wisconsin | 54311 | United States |
| 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. |
| Auxora vs. placebo for the treatment of severe COVID-19 pneumonia: a Phase 2 study (Part 2, double-blinded) | View source |
Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. |
| FG002 | Auxora (Part 2) | Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: 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. |
| FG003 | Placebo (Part 2) | Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be 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. |
| Part 1: Low -Flow Oxygen Therapy Part 2: PaO2/FiO2 </= 200 |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Standard of Care (Part 1) | Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Mean | Standard Deviation | years |
| ||||||||||||||
| Sex: Female, Male | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Count of Participants | Participants |
| |||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Category "More than one race" also includes patients who indicated "other" | Count of Participants | Participants |
| |||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| 65+years of age | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Count of Participants | Participants |
| |||||||||||||||
| Body Mass Index | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Mean | Standard Deviation | kg/m^2 |
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| Time from symptom onset | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Mean | Standard Deviation | Days |
| ||||||||||||||
| High-flow nasal cannula use (HFNC) | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Count of Participants | Participants |
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| Baseline imputed PaO2/FiO2 value | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Mean | Standard Deviation | Ratio |
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| Baseline imputed PaO2/FiO2=/<100 | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Count of Participants | Participants |
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| Baseline imputed PaO2/FiO2 101-200 | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Count of Participants | Participants |
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| C-reactive protein (CRP) | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Mean | Standard Deviation | mg/L |
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| Ferritin | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Mean | Standard Deviation | ng/mL |
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| Hypertension | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Count of Participants | Participants |
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| Diabetes | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Count of Participants | Participants |
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| Hyperlipidemia | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Count of Participants | Participants |
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| Former smoker | For Part 1 of the study, all 30 treated patients were included in the MITT population, and 26 patients in the low-flow (severe COVID-19 pneumonia) arm were included in the efficacy evaluable population.In Part 2, 261 patients (131 placebo and 130 Auxora patients) with a baseline imputed PaO2/FiO2 ≤200 group were included in the Efficacy Analysis Set 281 patients (140 placebo and 141 Auxora patients) were included in the Safety Analysis Set | Count of Participants | Participants |
|
| 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 | 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. | Posted | Median | 95% Confidence Interval | Days | From start of first infusion of study drug to day 60 |
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| Secondary | Number of Participants Who Have Died at Day 30 (Mortality) | Posted | Count of Participants | Participants | Day 30 |
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| Secondary | Number of Participants Who Have Died at Day 60 (Mortality) | Posted | Count of Participants | Participants | Day 60 |
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| Secondary | Number of Participants Requiring Invasive Mechanical Ventilation or Dying (Part 1) | Posted | Count of Participants | Participants | From start of first infusion of study drug and up to Day 28 |
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| Secondary | Proportion of Patients Requiring Invasive Mechanical Ventilation or Dying (Part 2) | Posted | Number | 95% Confidence Interval | Proportion of Participants | from start of first infusion of study drug and up to day day 60 |
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| Secondary | Proportion of Patients Requiring Invasive Mechanical Ventilation (Part 2) | Posted | Number | 95% Confidence Interval | Proportion of participants | from start of first infusion of study drug and up to day Day 60 |
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| 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 | Posted | Mean | Standard Deviation | score on a scale | from start of first infusion of study drug and up to day 28 |
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| 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 | Posted | Count of Participants | Participants | from start of first infusion of study drug hrough Day 60 |
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| Secondary | Change in PaO2/FiO2 (Part 1) | Measures of PaO2/FiO2 ratio | Posted | Mean | Standard Deviation | ratio of the arterial partial pressure o | From start of first infusion of study drug through Day 28 |
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| Secondary | Number of Days in the Hospital(Part 1) | Time to discharge alive from hospital | Posted | Median | 95% Confidence Interval | Days | From start of first infusion of study drug through Discharge up to 28 days |
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| Secondary | Number of Days in the Hospital (Part 2) | Number of days in the hospital during the first 28 days of the study with a baseline imputed PaO2/FiO2 \ | Posted | Least Squares Mean | 95% Confidence Interval | Days | from admission into the hospital until discharge from the hospital up to 60 days |
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| Secondary | Number of Days in the Intensive Care Unit (ICU) (Part 2) | Number of ICU days during the first 28 days of the study in patients with a baseline imputed PaO2/FiO2 \ | Posted | Least Squares Mean | Inter-Quartile Range | Days | from admission into ICU until discharge from ICU up to 60 days |
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| Secondary | Days Alive and Free of Mechanical Ventilation (Part 1) | Posted | Mean | Standard Deviation | Days | From randomization through Day 28 |
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| Secondary | Number of Participants Considered Recovered (Part 1) | Recovery is defined as a 6, 7, or 8 on the 8 point ordinal scale | Posted | Count of Participants | Participants | From start of first infusion of study drug through Day 28 |
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| Secondary | CM4620-IE Plasma Concentration (Part 2) | Concentration measured using a validated assay | Patients with a viable PK sample at 72 hours | Posted | Geometric Mean | Standard Deviation | ng/mL | From start of first infusion of study drug through 72 hours |
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| Secondary | Percentage of Patients With Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) | 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 | Posted | Number | percentage of patients | From start of first infusion of study drugand through day 60 |
|
Adverse event (AE) data were collected from randomization through Day 60
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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 | 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 | 2 | 20 | 6 | 20 | 15 | 20 |
| EG001 | Standard of Care (Part 1) | Patients were randomized 2:1 to receive CM4620-IE or continue with the local standard of care. | 2 | 10 | 5 | 10 | 8 | 10 |
| EG002 | Auxora (Part 2) | Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: 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. | 18 | 141 | 34 | 141 | 69 | 141 |
| EG003 | Placebo (Part 2) | Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be 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. | 27 | 140 | 49 | 140 | 68 | 140 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Leukocytosis | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
| ||
| Cardiac arrest | Cardiac disorders | Systematic Assessment |
| ||
| Cardio-Respiratory Arrest | Cardiac disorders | Systematic Assessment |
| ||
| Conduction Disorder | Cardiac disorders | Systematic Assessment |
| ||
| Coronary Artery Occlusion | Cardiac disorders | Systematic Assessment |
| ||
| Pulseless Electrical Activity | Cardiac disorders | Systematic Assessment |
| ||
| Sinus Tachycardia | Cardiac disorders | Systematic Assessment |
| ||
| Gastrointestinal Haemorrhage | Gastrointestinal disorders | Systematic Assessment |
| ||
| Ileus | Gastrointestinal disorders | Systematic Assessment |
| ||
| Bacterial Pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Klebsiella Bacteraemia | Infections and infestations | Systematic Assessment |
| ||
| Pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Pneumonia Klebsiella | Infections and infestations | Systematic Assessment |
| ||
| Pneumonia Staphylococcal | Infections and infestations | Systematic Assessment |
| ||
| Pseudomonal Bacteraemia | Infections and infestations | Systematic Assessment |
| ||
| Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Septic shock | Infections and infestations | Systematic Assessment |
| ||
| Staphylococcal Bacteraemia | Infections and infestations | Systematic Assessment |
| ||
| Staphylococcal Infection | Infections and infestations | Systematic Assessment |
| ||
| Viral Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Alanine Aminotransferase Increased | Investigations | Systematic Assessment |
| ||
| Aspartate Aminotransferase Increased | Investigations | Systematic Assessment |
| ||
| Decreased Oxygen Saturation | Investigations | Systematic Assessment |
| ||
| Increased Liver Function Test | Investigations | Systematic Assessment |
| ||
| Brain Injury | Nervous system disorders | Systematic Assessment |
| ||
| Cerebral Haemorrhage | Nervous system disorders | Systematic Assessment |
| ||
| Cerebrovascular Accident | Nervous system disorders | Systematic Assessment |
| ||
| Acute Kidney Injury | Renal and urinary disorders | Systematic Assessment |
| ||
| ARDS | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Acute Respiratory Failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Organising Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pneumonia Aspiration | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pneumothorax Spontaneous | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Respiratory Distress | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Deep Vein Thrombosis | Vascular disorders | Systematic Assessment |
| ||
| Orthostatic Hypotension | Vascular disorders | Systematic Assessment |
| ||
| Shock | Vascular disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood triglycerides increased | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
| ||
| Increased transaminases | Investigations | Systematic Assessment |
| ||
| DVT | Vascular disorders | Systematic Assessment |
| ||
| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Hypoglycaemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Blood Alkaline Phosphatase Increased | Investigations | Systematic Assessment |
| ||
| Blood Creatine Phosphokinase Increased | Investigations | Systematic Assessment |
| ||
| Hypotension | Vascular disorders | Systematic Assessment |
| ||
| Abdominal Pain | General disorders | Systematic Assessment |
| ||
| Chills | General disorders | Systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Decubitus Ulcer | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Systematic Assessment |
| ||
| Encephalopathy | Nervous system disorders | Systematic Assessment |
| ||
| Gastrointestinal Haemorrhage | Gastrointestinal disorders | Systematic Assessment |
| ||
| Hypomagnesaemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Normocytic Anaemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Seizure | Nervous system disorders | Systematic Assessment |
|
The number of patients who participated in the biomarker collection was not sufficient to provide / record meaningful results.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sudarshan Hebbar, MD | CalciMedica, Inc. | 8168387105 | sudarshan@calcimedica.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 17, 2021 | Jul 25, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D011014 | Pneumonia |
| D000086382 | COVID-19 |
| D018352 | Coronavirus Infections |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D011024 | Pneumonia, Viral |
| D014777 | Virus Diseases |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| C000721808 | zegocractin |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
|
|
|
|
|
|
Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: 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. |
| OG003 | Placebo Day 12 | Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be 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. |
| OG004 | Auxora Day 30 | Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: 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. |
| OG005 | Placebo Day 30 | Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be 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. |
| OG006 | Auxora Day 60 | Patients will be randomized 1:1 to receive either Auxora or placebo Auxora: 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. |
| OG007 | Placebo Day 60 | Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be 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. |
|
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Patients will be randomized 1:1 to receive either Auxora or placebo Placebo: Placebo will be 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. |
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