A study to evaluate the safety and efficacy of XAV-19 in patients with COVID-19 induced moderate pneumonia

INTERVENTION: Product Name: XAV‐19 Product Code: XAV‐19 Pharmaceutical Form: Solution for infusion Pharmaceutical form of the placebo: Solution for infusion Route of administration of the placebo: Intravenous use CONDITION: Moderate COVID‐19 ; MedDRA version: 23.0 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: Phase 2a:; The primary objective of the study is to evaluate the Antibody titers of; XAV‐19 treated patients versus placebo treated patients at Day 8.; Phase 2b:; The primary objective of the study is to compare duration until weaning; supplemental oxygen in the two groups of treatment. Primary end point(s): Phase 2a:; The primary endpoint is pharmacokinetic measurement of the antibody; titer of XAV‐19 measurements of all treated patients and of all patients; in the placebo group at Day 8 (3 days after the last administration).; Phase 2b:; Time to weaning of supplemental oxygen.; If patient is still on oxygen at D15 or if the patient is weaned but put; back on oxygen then the delay will be censored at 15 days. Secondary Objective: Phase 2a:; a)Characterize pharmacokinetics (PK) of XAV‐19 infected patients over; the time from D1 to D29; b)Evaluate the Antibody titers of XAV‐19 and to compare Group 1; treated patients versus Group 2 treated patients at Day 8.; c)Assess safety and tolerability of XAV‐19 vs. placebo and between; group 1 and group 2 treated patients over 29 days.; d)Describe groups of patients according to clinical variables; Phase 2b:; a)Evolution of National Early Warning Score (NEWS); b)Changes in the 7‐point ordinal scale between baseline and Day 15; c)Improvement of one category from admission using the 7‐point ordinal; scale; d)Normalization of fever; e)Duration of oxygen therapy over 29 days; f)Oxygen requirement over 29 days; g)Transfer to ICU with need for IMV or high flow O2; h)Hospital length of stay; i)All cause of mortality; j)Safety of XAV‐19 Timepoint(s) of evaluation of this end point: Phase 2a: Day 8; Phase 2b: Day 15 SECONDARY OUTCOME: Secondary end point(s): Phase 2a:; The secondary endpoints are :; a)Pharmacokinetic analysis: Antibody titer measurements at Day 1 (predose,; post‐dose), at Day 5 (pre‐dose, post‐dose), Day 8, Day 15, and Day; 29.; b)The antibody titer of XAV‐19 measurements in Group 1 treated; patients and Group 2 treated patients at Day 15.; c)Safety of XAV‐19 evaluated as:; •Occurrence of all suspected XAV‐19 related adverse effects and; incidence of serious adverse events; •Proportion of participants with treatment emergent adverse events; leading to study drug discontinuation; •Incidence of major or bacterial or fungal infections; •Incidence of hypersensitivity reactions and infusion reactions; •White cell count, hemoglobin, platelets, creatinine, ALT, AST, on D1, D3,; D5, D8, D15 and D29; •SARS‐CoV‐2 viral load over time (D1‐D29), as collected by; nasopharyngeal swab samples; •Time to RT‐PCR virus negativity in nasopharyngeal swab samples; d)Clinical aspects:; •Duration of supplemental oxygen; •Transfer to intensive care unit with need for invasive mechanical; ventilation or high flow oxygen; •Normalization of fever = 24 hours: clinical assessment every day from; Day 1 to Day 14. Evaluation to be performed between 8 and 12 am, Day; X evaluation will consider the higher value during Day X‐1 (8 am to 8; am); ‐ Normal fever (= 37.8° C tympanic or = 36.6°C axillary or = 37.2°C oral; taken 4 hours apart from antipyretic administration) each day and time; to resolution of fever for at least 48 hours; •Biomarkers : CRP, Ferritin; •Ordinal scale assessed at Day 15. The 7‐point ordinal scale is an; assessment of the clinical status at the first assessment on day 15. The; scale is as follows:; 1.Not hospitalized, no limitations on activities;; 2.Not hospitalized, limitations on activities;; 3.Hospitalized, not requiring supplemental oxygen;; 4.Hospitalized, requiring supplemental oxygen;; 5.Hospitalized, on non‐invasive ventilation or high flow O2 devices;; 6.Hospitalized, on invasive mechanical ventilation or ECMO;; 7.Death.; •Hospital length of stay; ; Phase 2b:; The secondary endpoints are:; a)National Early Warning Score (NEWS) at Day 15 and every Day; between D1 and D15; b)Clinical status using the 7‐point ordinal scale assessed at D3,D5, D8,; D11, D15, and D29; c)Time to improvement of one category from admission using the 7‐; point ordinal scale; d)Time to first fever normalization (criteria for normalization:; temperature < 36.6°C armpit, < 37.2°C oral, < 37.8°C rectal or; tympanic); e)Duration of oxygen therapy over 29 days; f)Oxygen requirement <4L/min or >4L/min to achieve a SpO2 > 94%; between the two groups over 29 days; g)Incidence and duration of non‐invasive ventilation or high flow oxygen; devices, of invasive mechanical ventilation during the study; h)Hospital length of stay; i)All cause mortality at D29; j)Safety of XAV‐19 evaluated as:; •Occurrence of all suspected XAV‐19 related adverse effects; or Incidence of serious adverse events; •Proportion of participants with treatment emergent adverse events; leading to study drug discontinuation; •Incidence of major or opportunistic bacterial or fungal infections; •Incidence of hypersensitivity reactions and infusion reactions; •White cell count, hemoglobin, platelets, creatinine, ALT, AST, on D1, D3,; D5, D8, D11, D15 and D29; •SARS‐CoV‐2 viral load over time (D1‐D29), as collected by; nasopharyngeal swab samples; •Time to RT‐PCR virus negativity in nasopharyngeal swab samples Timepoint(s) of evaluation of this end point: Phase 2a:; a)Pharmacokinetic analysis: at Day 1 (pre‐dose, post‐dose), at Day 5; (pre‐dose, post‐dose), Day 8, Day 15, and Day 29.; b)The antibody titer of XAV‐19 measurements at Day 15.; c)Safety of XAV‐19 evaluated at every visit; d)Clinical aspects at every visit; Phase 2b:; a)NEWS every Day between D1 and D15; b)Clinical status assessed at D3,D5, D8, D11, D15, and D29; c)Time to improvement using the 7‐point ordinal scale at every visit; d)Time to first fever normalization at every visit; e)Duration of oxygen therapy at every visit; f)Oxygen requirement at every visit; g)Incidence and duration of non‐invasive ventilation or high flow oxygen; devices at every visit; h)Hospital length of stay at every visit; i)All cause mortality at D29; j)Safety of XAV‐19 evaluated at every visit INCLUSION CRITERIA: 1.Willing and able to provide written informed consent prior to performing study procedures 2.Male or female = 18 years 3.Hospitalized for COVID‐19 4.Positive SARS‐CoV‐2 RT‐PCR in any body specimen (nasopharynx, saliva, sputum) = 10 days before enrolment 5.Evidence of pulmonary involvement (on lung examination [rales/crackles] and/or chest‐imaging [Chest X‐ray or computed tomography]) 6.Requiring O2 supplement with SpO2 = 6L/min at screening 7.Requiring O2 supplementation with SpO2 = 94% on O2 therapy at screening 8.First onset of COVID‐19 symptoms = 10 days, among fever and/or chills, headache, myalgias, cough, shortness of breath, whichever as occurred fist 9.WOCBP must have a negative urinary pregnancy test the day of inclusion 10.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