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

A Single-Blind Dose-Ranging Pharmacodynamic Study of Auxora for the Treatment of Patients With Critical COVID-19 Pneumonia

This is a single-blind study of Auxora in patients with critical COVID-19 pneumonia, consisting of up to 3 cohorts of escalating dose. The main goal was to assess pharmacodynamic parameters of immune response, while also assessing safety and tolerability of the drug in this patient population.

The primary objective of this study was to assess the pharmacodynamic response of bronchoalveolar lavage (BAL) T cell/monocyte subsets and chemokine release to various doses of Auxora in patients with critical COVID-19 pneumonia. Other objectives included assessment of safety and tolerability of Auxora in patients with critical COVID-19 pneumonia, as well as pharmacokinetic profile of Auxora in these patients. Efficacy was also to be examined based on all-cause mortality at day 60, number of days on mechanical ventilation after randomization, number of days in the hospital after randomization, and number of days in the ICU after randomization.

Patients were randomized 3:1 to Auxora or Placebo. The first 4 patients were enrolled in Cohort 1 (3 Auxora, 1 Placebo). If dose escalation occurred, the next 4 patients were to be enrolled in Cohort 2. If dose escalation occurred again, the next 8 patients were to be enrolled in Cohort 3. The decision to escalate dosing was made by CalciMedica in consultation with the PI and after the review of safety events in Cohorts 1 and 2.

(Note: Trial terminated early after the first patient was enrolled in Cohort 3 due to lack of new Covid-19 hospitalizations.)

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;

2. Moderate ARDS characterized by the following criteria:

   • Invasive mechanical ventilation with a minimum PEEP of 5 cm H2O;
   • PaO2/FiO2 ≤200 that may be estimated from pulse oximetry or determined by arterial blood gas;
   • No evidence of volume overload or heart failure;

3. The patient is ≥18 years of age at the time of consent;

4. QTcF interval ≤ 440 milliseconds;

5. 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 study drug;

6. 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 study drug. A male patient must not donate sperm for 39 months;

7. 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. ECMO;

3. Suspected septic shock;

4. The patient has a history of:

   • Organ or hematologic transplant;
   • HIV;
   • Active hepatitis B or hepatitis C infection;

5. Current treatment with:

   • Chemotherapy;
   • Immunosuppressive medications or immunotherapy (see Section 5.3 for list of prohibited immunosuppressive medications and immunotherapy) at the time of consent;
   • Hemodialysis or Peritoneal Dialysis;

6. The patient is known to be pregnant or is nursing;

7. Currently participating in another study of an investigational drug or therapeutic medical device at the time of consent;

8. Allergy to eggs or any of the excipients in study drug.