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

Sponsor

CalciMedica, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT04345614

Collaborator

(none)

284

Enrollment

Locations

Arms

15.7

Actual Duration (Months)

16.7

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia	Drug: Auxora Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

284 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Matching placebo

Primary Purpose:

Treatment

Official Title:

A Randomized Double Blind, Placebo-Controlled Study of Auxora for the Treatment of Severe COVID-19 Pneumonia (CARDEA)

Actual Study Start Date :

Apr 8, 2020

Actual Primary Completion Date :

Jun 28, 2021

Actual Study Completion Date :

Jul 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Auxora Patients will be randomized 1:1 to receive either Auxora or placebo	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 Names: CM4620-Injectable Emulsion (IE)
Placebo Comparator: Placebo Patients will be randomized 1:1 to receive either Auxora or placebo	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 Names: Placebo-Injectable Emulsion

Arm

Intervention/Treatment

Experimental: Auxora

Patients will be randomized 1:1 to receive either Auxora or placebo

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 Names:

CM4620-Injectable Emulsion (IE)

Placebo Comparator: Placebo

Patients will be randomized 1:1 to receive either Auxora or placebo

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 Names:

Placebo-Injectable Emulsion

Outcome Measures

Primary Outcome Measures

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

Proportion of patients who have died at day 60 (mortality) [Day 60]
Proportion of patients who have died at day 30 (mortality) [Day 30]
Proportion of patients requiring invasive mechanical ventilation or dying [from start of start of first infusion of study drug and up to day 60]
Proportion of patients requiring invasive mechanical ventilation [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 [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 [from admission into the hospital until discharge from the hospital]
Number of days in the Intensive Care Unit (ICU) [from admission into ICU until discharge from ICU]
Incidence, intensity and relationship of treatment emergent adverse events (TEAE) and serious adverse events (SAE) [from randomization and through day 60]
CM4620-IE serum concentration [enrollment through 72 hours]
Concentration measured using a validated assay

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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;

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;
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;

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;
The patient is ≥ 18 years of age;
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;
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;
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:

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:
Organ or hematologic transplant;
HIV;
Active hepatitis B, or hepatitis C infection;
Current treatment with:
Chemotherapy;
Immunosuppressive medications or immunotherapy (Section 5.3 for list of prohibited immunosuppressive medications and immunotherapy) at the time of consent;
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Long Beach Memorial	Long Beach	California	United States	90806
2	University of Southern California / LA County	Los Angeles	California	United States	90033
3	Sharp Memorial San Diego	San Diego	California	United States	92123
4	National Jewish Health / St. Joseph's Hospital	Denver	Colorado	United States	80220
5	Northwestern University	Chicago	Illinois	United States	60611
6	Baton Rouge General	Baton Rouge	Louisiana	United States	70809
7	Maine Medical Center	Portland	Maine	United States	04102
8	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
9	Henry Ford Hospital	Detroit	Michigan	United States	48202
10	Sinai Grace	Detroit	Michigan	United States	48235
11	Methodist Hospital	Saint Louis Park	Minnesota	United States	55426
12	Regions Hospital	Saint Paul	Minnesota	United States	55101
13	Texas Tech University Medical Center	El Paso	Texas	United States	79905
14	John Peter Smith Hospital	Fort Worth	Texas	United States	76104
15	Houston Methodist Hospital	Houston	Texas	United States	77030
16	Virginia Commonwealth University	Richmond	Virginia	United States	23298
17	Aurora Baycare	Green Bay	Wisconsin	United States	54311