Study to Evaluate the Safety and Efficacy of XAV-19 in Patients With COVID-19 Induced Moderate Pneumonia

For the first set of statistical analyses, to allow early reporting of primary and secondary endpoints at D15, the blind will be partially broken once all patients have completed Day 29. Except for statisticians, only the principal investigator and the scientific coordinator will have access to the full data set for the analysis of the primary and secondary endpoints up to day 29. The database will be partially locked (with all data up to day 29) as neither monitors nor investigators will be informed of the unblinding until the final data for day 60 is completed and the final database is locked.

Phase 2a:

Inclusion criteria

• Willing and able to provide written informed consent prior to performing study procedures
• Male or female ≥ 18 years and ≤ 85 years
• Hospitalized for COVID-19
• Positive SARS-CoV-2 RT-PCR in any body specimen (nasopharynx, saliva, sputum) ≤ 10 days before enrolment
• Evidence of pulmonary involvement (on lung examination [rales/crackles] and/or chest-imaging [Chest X-ray or computed tomography])
• Requiring O2 supplement ≤ 6L/min at screening
• Requiring O2 supplementation with SpO2 ≥ 94% on O2 therapy at screening
• First onset of COVID-19 symptoms ≤ 10 days, among fever and/or chills, headache, myalgias, cough, shortness of breath, whichever as occurred fist
• WOCBP must have a negative urinary pregnancy test the day of inclusion
• All sexually active male subjects must agree to use an adequate method of contraception throughout the study period and for 90 days after the last dose of study drug and agree to no sperm donation until the end of the study, or for 90 days after the last dose of XAV-19, whichever is longer
• Patients with French social security

Exclusion criteria

• Evidence of multiorgan failure (severe COVID-19)
• Mechanically ventilated (including ECMO)
• Receipt of immunoglobulins or any blood products in the past 30 days
• Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the investigator, would affect subject safety and/or compliance
• End-stage renal disease (eGFR < 15 ml/min/1,73 m2)
• Child-Pugh C stage liver cirrhosis
• Decompensated cardiac insufficiency
• History of active drug abuse
• Known allergy, hypersensitivity, or intolerance to the study drug, or to any of its components
• Females of childbearing potential without contraceptive method, or with positive pregnancy test, breastfeeding, or planning to become pregnant during the study period
• Current documented and uncontrolled bacterial infection.
• Prior severe (grade 3) allergic reactions to plasma transfusion
• Patient participating in another interventional clinical trial
• Life expectancy estimated to be less than 6 months
• Patient under guardianship or trusteeship

Phase 2b:

Inclusion criteria

• Willing and able to provide written informed consent prior to performing study procedures
• Male or female ≥ 18 years
• Hospitalized for COVID-19
• Documentation of SARS-Cov-2 infection before enrolment, by positive SARS-CoV-2 RT-PCR or antigen in any body specimen (nasopharynx, oropharynx, saliva, sputum, bronchoalveolar lavage …) before enrolment
• Evidence of pulmonary involvement (on lung examination [rales/crackles] and/or chestimaging [Chest X-ray or computed tomography])
• Requiring O2 supplement ≤ 6L/min at screening
• Requiring O2 supplementation with SpO2 ≥ 92% on O2 therapy at screening (or ≥ 90

% if chronic obstructive pulmonary disease)

• First onset of COVID-19 symptoms ≤ 14 days, among fever and/or chills, headache, myalgias, cough, shortness of breath, whichever as occurred fist (other symptoms such as asthenia not to be considered in this list)
• WOCBP must have a negative urinary pregnancy test the day of inclusion
• All sexually active male subjects must agree to use an adequate method of contraception throughout the study period and for 90 days after the last dose of study drug and agree to no sperm donation until the end of the study, or for 90 days after the last dose of XAV-19, whichever is longer
• Patients with French social security

Exclusion criteria

• Evidence of multiorgan failure (severe COVID-19)
• Mechanically ventilated (including ECMO)
• Receipt of immunoglobulins or any blood products in the past 30 days
• Psychiatric or cognitive illness or recreational drug/alcohol use that in the opinion of the investigator, would affect subject safety and/or compliance
• End-stage renal disease (eGFR < 15 ml/min/1,73 m2)
• Child-Pugh C stage liver cirrhosis
• Decompensated cardiac insufficiency
• Known allergy, hypersensitivity, or intolerance to the study drug, or to any of its components
• Females of childbearing potential without contraceptive method, or with positive pregnancy test, breastfeeding, or planning to become pregnant during the study period
• Current documented and uncontrolled bacterial infection.
• Prior severe (grade 3) allergic reactions to plasma transfusion
• Patient participating in another interventional clinical trial
• Life expectancy estimated to be less than 6 months
• Patient under guardianship or trusteeship
• Patient already included
• Prior hospitalisation in intensive care unit for the current covid-19 episode