Efficacy and safety of XAV-19 for the treatment of moderate to severe COVID-19

INTERVENTION: Product Name: XAV‐19 Product Code: XAV‐19 Pharmaceutical Form: Solution for injection INN or Proposed INN: Anti‐viral immunoglobulins Current Sponsor code: XAV‐19 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Intravenous use CONDITION: Moderate to severe COVID‐19 ; MedDRA version: 23.1 Level: PT Classification code 10084460 Term: COVID‐19 treatment System Organ Class: 10042613 ‐ Surgical and medical procedures Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: The primary objective is to compare the clinical efficacy of XAV‐19 to that of placebo in patients with COVID‐19. Primary end point(s): The primary endpoint is the proportion of patients with an aggravation of COVID‐19 within 8 days after treatment. The aggravation is defined as a worsening of the score of at least 1 point on the WHO 7‐point ordinal scale compared to the score on the WHO‐7 ordinal scale at randomization. Secondary Objective: The secondary objectives are:; ‐ to compare the change in clinical parameters (fever, respiratory rate, shortness of breath, thoracic pain, SpO2, supplemental O2) in patients treated with XAV‐19 to that in patients treated with Placebo,; ‐ to compare the length of hospital stay of patients treated with XAV‐19 to that of patients treated with Placebo,; ‐ to compare the viral status of patients treated with XAV‐19 to that of patients treated with Placebo, ; ‐ to compare the safety profile in patients with COVID‐19 treated with XAV‐19 to that in patients treated with Placebo; Timepoint(s) of evaluation of this end point: Within 8 days after treatment. SECONDARY OUTCOME: Secondary end point(s): The secondary endpoints are:; • Change in clinical parameters between randomization and Day 3, 5, 8 and 15: fever (>38°C), respiratory rate, SpO2, supplemental O2, ; • Change in severity, on Common Terminology Criteria of Adverse Events (CTCAE) scale, between randomization and Day 3, 5, 8 and 15: shortness of breath and thoracic pain (See Appendix 12.2),; • Duration of patient’s requirement in supplemental O2, ; • Duration of aggravation; • Length of hospital stay,; • Clinical status at Day 3 and Day 15 using the WHO 7‐point ordinal scale for COVID‐19,; • Viral status: RT‐PCR for SARS‐CoV‐2 (positive/negative) at randomization and on Day 8 or at the end of follow‐up, whichever comes first; • Viral load (if local practice enables it): RT‐qPCR for SARS‐CoV‐2 at randomization and on Day 8 or at the end of follow‐up, whichever comes first; • Proportion of patients referred to ICU between randomization and Day 3, 5, 8 and 15,; • Proportion of patients with need for mechanical ventilation at randomization and at Day 3, 5, 8 and 15,; • Eight‐ and 15‐day survival rates, defined by the crude proportion of patients still alive 8 or 15 days after randomization; • Safety parameters (i.e. adverse events, hypersensitivity or allergy, white and red blood cells, liver enzymes, creatinine) Timepoint(s) of evaluation of this end point: Between randomization and Day 3, 5, 8 and 15. INCLUSION CRITERIA: I1) Male or female patient aged 18 years or over, weighing >50 Kg and <120 Kg, at the time of signing the informed consent, I2) Patient presenting in a specialized or an emergency unit I3) Patient presenting signs of pneumonia evidenced by at least 1 of the following: auscultation, chest X‐Ray, CT scan OR presenting COVID‐19 related symptoms having started less than 10 days prior to screening visit, including at least 2 of the following: fever, cough, sore throat or nasal discharge, dyspnea (shortness of breath), thoracic pain, headache or fatigue, myalgia, anosmia, dysgeusia, diarrhea, nausea I4) Patient with SpO2 > 90% (at ambient air) I5) Patient with a first positive SARS‐CoV‐2 test (RT‐PCR, RT‐qPCR or antigen test) in the last 10 days or at screening I6) Women of childbearing potential (WOCBP) must have a negative urine pregnancy test at screening and use a highly effective1 birth control until 90 days after the administration of study dru