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

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ClinicalTrials.gov Identifier: NCT04345614
Recruitment Status : Recruiting
First Posted : April 14, 2020
Last Update Posted : April 12, 2021
Sponsor:
Information provided by (Responsible Party):
CalciMedica, Inc.

Tracking Information
First Submitted Date  ICMJE April 7, 2020
First Posted Date  ICMJE April 14, 2020
Last Update Posted Date April 12, 2021
Actual Study Start Date  ICMJE April 8, 2020
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 8, 2021)
Number of days from the Start of the First Infusion of Study Drug (SFISD) to recovery [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 13, 2020)
  • Improvement on a 7-point Ordinal Scale [ Time Frame: Upon enrollment into the study through hospital discharge, up to day 28 ]
    The ordinal scale is an assessment of the clinical status at a given day. Each day, the worst score from the previous day will be recorded. The scale is as follows: 1. Death 2. Hospitalized, on invasive mechanical ventilation or ECMO 3. Hospitalized, on non-invasive ventilation or high flow oxygen devices 4. Hospitalized, requiring low flow supplemental oxygen 5. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care (other than per protocol study drug administration) 7. Not hospitalized
  • Incidence of treatment-emergent adverse events (TEAE) (safety and tolerability) [ Time Frame: from enrollment and up to 60 days ]
    Defined as the number of participants who experience TEAEs with investigator-specified relationship to CM4620-IE and assessment of severity.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2021)
  • Proportion of patients who have died at day 60 (mortality) [ Time Frame: Day 60 ]
  • Proportion of patients who have died at day 30 (mortality) [ Time Frame: Day 30 ]
  • Proportion of patients requiring invasive mechanical ventilation or dying [ Time Frame: from start of start of first infusion of study drug and up to day 60 ]
  • Proportion of patients requiring invasive mechanical ventilation [ Time Frame: from start of start of first infusion of study drug and up to day 60 ]
  • Differences in outcomes as measured by an 8-point ordinal scale [ Time Frame: from randomization through Days 12 and 30 ]
    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
  • Number of days in the hospital [ Time Frame: from admission into the hospital until discharge from the hospital ]
  • Number of days in the Intensive Care Unit (ICU) [ Time Frame: from admission into ICU until discharge from ICU ]
  • Incidence, intensity and relationship of treatment emergent adverse events (TEAE) and serious adverse events (SAE) [ Time Frame: from randomization and through day 60 ]
  • CM4620-IE serum concentration [ Time Frame: enrollment through 72 hours ]
    Concentration measured using a validated assay
Original Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2020)
  • Change in estimated PaO2/FiO2 [ Time Frame: from enrollment and up to day 28 ]
    Defined as the change in the ratio of arterial oxygen partial pressure to fractional inspired oxygen
  • Number of days alive and free of mechanical ventilation [ Time Frame: from enrollment and up to day 60 ]
    Defined as the number of days that a participant is both alive and free of mechanical ventilation
  • Time to discharge alive from hospital [ Time Frame: From day 1 of hospital admission to hospital discharge, up to day 28 ]
    Defined as the number of days from hospital admission to discharge alive from the hospital
  • Number of patients alive on day 30 and day 60 [ Time Frame: Day 30 and day 60 ]
  • Change in interleukin (IL)-6 level [ Time Frame: from enrollment until day 10 ]
    Measurement of IL-6 levels in patient blood
  • Change in IL-17 level [ Time Frame: from enrollment until day 10 ]
    Measurement of IL-17 levels in patient blood
  • Change in tumor necrosis factor-alpha level [ Time Frame: from enrollment until day 10 ]
    Measurement of tumor necrosis factor-alpha in patient blood
  • Change in cytokine levels [ Time Frame: from enrollment until day 10 ]
    Measurement of cytokines in patient blood
  • CM4620-IE serum concentration [ Time Frame: enrollment through 72 hours ]
    Concentration measured using a validated assay
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Auxora in Patients With Severe COVID-19 Pneumonia
Official Title  ICMJE A Randomized Double Blind, Placebo-Controlled Study of Auxora for the Treatment of Severe COVID-19 Pneumonia (CARDEA)
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 will consist of a randomized, double blind, placebo-controlled (RCT) study that will evaluate 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 will be capped at 26. 320 patients with a PaO2/FiO2 ≤200 will be enrolled. Patients with an estimated PaO2/FiO2 of 75-200 will be stratified to ensure balanced randomization between the Auxora and placebo arms. Subgroup analyses will be 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 will be 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 will be 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 will be allowed. The infusion of Auxora will start within 12 hours from the time the patient or LAR provides 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 will be 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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Matching placebo
Primary Purpose: Treatment
Condition  ICMJE Pneumonia
Intervention  ICMJE
  • Drug: 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.
    Other Name: CM4620-Injectable Emulsion (IE)
  • Drug: 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.
    Other Name: Placebo-Injectable Emulsion
Study Arms  ICMJE
  • Experimental: Auxora
    Patients will be randomized 1:1 to receive either Auxora or placebo
    Intervention: Drug: Auxora
  • Placebo Comparator: Placebo
    Patients will be randomized 1:1 to receive either Auxora or placebo
    Intervention: Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 8, 2021)
346
Original Estimated Enrollment  ICMJE
 (submitted: April 13, 2020)
60
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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. Extracorporeal membrane oxygenation (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 of:

    1. Organ or hematologic transplant;
    2. HIV;
    3. Active hepatitis B, or hepatitis C infection;
  12. Current treatment with:

    1. Chemotherapy;
    2. Immunosuppressive medications or immunotherapy (Section 5.3 for list of prohibited immunosuppressive medications and immunotherapy) at the time of consent;
    3. 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sudarshan Hebbar, MD 816-838-7105 sudarshan@calcimedica.com
Contact: Ken Stauderman, PhD 858-353-2726 ken@calcimedica.com
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04345614
Other Study ID Numbers  ICMJE CM4620-204
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party CalciMedica, Inc.
Study Sponsor  ICMJE CalciMedica, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Sudarshan Hebbar, MD CalciMedica, Inc.
PRS Account CalciMedica, Inc.
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP