Clinical trial NCT04661540: A Study of Auxora in Patients With Critical COVID-19 Pneumonia
Official title: A Single-Blind Dose-Ranging Pharmacodynamic Study of Auxora for the Treatment of Patients With Critical COVID-19 Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pneumonia
Keywords: COVID-19
Coronavirus
Pneumonia
Calcium Release-Activated Calcium Channel (CRAC) Inhibitors
CM4620
Auxora
Lead sponsor: CalciMedica, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Northwestern University
First posted: 2020-12-10
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a single-blind study consisting of up to 3 cohorts Patients will be randomized 3:1 to Auxora or Placebo. The first 4 patients will be enrolled in Cohort 1. If dose escalation occurs, the next 4 patients will be enrolled in Cohort 2 If dose escalation occurs, the next 8 patients will be enrolled in Cohort 3. The decision to escalate dosing will be made by CalciMedica in consultation with the PI and after the review of safety events in Cohorts 1 and 2.


Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of immune cells in BAL fluid and T cell activation will be assessed
timeFrame: Baseline Assessment up to 120 hours
measure: Impact of Auxora on the emergence of new clusters/cell types/cell states
timeFrame: Baseline Assessment up to 120 hours
measure: Impact of Auxora on detection of SARS-CoV-2 positive and negative strand RNA in infected cells
timeFrame: Baseline Assessment up to 60 days
Secondary outcomes:
measure: Plasma Levels of CM4620
timeFrame: From end of first infusion of study drug up to 144 hours
measure: Number of Days on Mechanical Ventilation after randomization
timeFrame: From randomization until patient is extubated assessed up to 60 days
measure: Number of Days in the Hospital after randomization
timeFrame: From randomization until discharge from the hospital assessed up to 60 days
measure: Number of Days in the Intensive Care Unit (ICU) after randomization
timeFrame: From randomization until discharge from ICU assessed up to 60 days
measure: Pre-defined changes in cardiac conduction assessed by ECG
timeFrame: From screening up to 144 hours
measure: Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From randomization up to 60 days
measure: Intensity and relationship of TEAEs and SAEs
timeFrame: From randomization up to 60 days
measure: Mortality
timeFrame: Randomization up to 60 days
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
Study officials:
References: