A Study of Auxora in Patients With Severe COVID-19 Pneumonia
- Conditions
- Pneumonia
- Interventions
- Drug: Auxora (Part 1)Drug: Standard of Care (Part 1)Drug: Auxora (Part 2)Drug: Placebo (Part 2)Drug: Placebo
- Registration Number
- NCT04345614
- Lead Sponsor
- CalciMedica, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 314
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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;
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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;
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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;
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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;
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The patient is ≥ 18 years of age;
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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;
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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;
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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.
- 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;
- Extracorporeal membrane oxygenation (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 of 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; c. 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;
- Allergy to eggs or any of the excipients in study drug.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Auxora (Part 1) Auxora (Part 1) Patients were randomized 1:1 to receive either Auxora or standard of care Standard of Care (Part 1) Standard of Care (Part 1) Patients were randomized 1:1 to receive either Auxora or standard of care Auxora (Part 2) Auxora (Part 2) Patients were randomized 1:1 to receive Auxora or Placebo Placebo (Part 2) Placebo (Part 2) Patients were randomized 1:1 to receive Auxora or Placebo Placebo Placebo Patients will be randomized 1:1 to receive either Auxora or placebo Auxora Auxora Patients will be randomized 1:1 to receive either Auxora or placebo
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 (ratio of the arterial partial pressure of oxygen to the fraction of inspired oxygen) and the change in value from baseline were evaluated over time
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
Trial Locations
- Locations (17)
Long Beach Memorial
🇺🇸Long Beach, California, United States
University of Southern California / LA County
🇺🇸Los Angeles, California, United States
Sharp Memorial San Diego
🇺🇸San Diego, California, United States
National Jewish Health / St. Joseph's Hospital
🇺🇸Denver, Colorado, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Baton Rouge General
🇺🇸Baton Rouge, Louisiana, United States
Maine Medical Center
🇺🇸Portland, Maine, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Sinai Grace
🇺🇸Detroit, Michigan, United States
Scroll for more (7 remaining)Long Beach Memorial🇺🇸Long Beach, California, United States