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

CalciMedica

Status and phase: Completed; Phase 2

Conditions: Pneumonia

Treatments: Drug: Placebo (Part 2); Drug: Auxora (Part 1); Drug: Standard of Care (Part 1); Drug: Auxora (Part 2)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04345614

CM4620-204

Details and patient eligibility

About

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.

Enrollment: 314 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

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 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; c. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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314 participants in 4 patient groups, including a placebo group

Auxora (Part 1)

Experimental group

Description:

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

Treatment:

Drug: Auxora (Part 1)

Standard of Care (Part 1)

Other group

Description:

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

Treatment:

Drug: Standard of Care (Part 1)

Auxora (Part 2)

Experimental group

Description:

Patients were randomized 1:1 to receive Auxora or Placebo

Treatment:

Drug: Auxora (Part 2)

Placebo (Part 2)

Placebo Comparator group

Description:

Patients were randomized 1:1 to receive Auxora or Placebo

Treatment:

Drug: Placebo (Part 2)