Evaluation of a combination of Masitinib and Isoquercetin in the Treatment of Hospitalized COVID-19 Patients

INTERVENTION: Product Name: Masitinib Product Code: AB1010 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Masitinib mesilate CAS Number: 790299‐79‐5 Current Sponsor code: AB1010 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Product Name: Masitinib Product Code: AB1010 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Masitinib mesilate CAS Number: 790299‐79‐5 Current Sponsor code: AB1010 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Product Name: Isoquercetin Product Code: IQC950AN Pharmaceutical Form: Capsule, soft Trade Name: Plaquenil 200 mg Pharmaceutical Form: Coated tablet CAS Number: 747‐36‐4 Current Sponsor code: SAR321068 Other descriptive name: HYDROXYCHLOROQUINE SULFATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ CONDITION: Hospitalized Moderate and Severe COVID‐19 Patients ; MedDRA version: 20.0 Level: SOC Classification code 10021881 Term: Infections and infestations System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: To compare the Safety and Efficacy of Hydroxychloroquine, and Standard of Care to a Combination of Masitinib, Isoquercetin, and Standard of Care for the Treatment of Hospitalized Moderate and Severe COVID‐19 Patients; Primary end point(s): • Clinical status of patients at day15 using the 7‐point ordinal scale.; ; The 7‐point ordinal scale for clinical status is: 1. Not hospitalized, no limitations on activities; 2.Not hospitalized, limitation on activities; 3. Hospitalized, not requiring supplemental oxygen; 4. Hospitalized, requiring supplemental oxygen; 5. Hospitalized, on non‐invasive ventilation or high flow oxygen devices; 6. Hospitalized, on invasive mechanical ventilation or ECMO; 7. Death.; Secondary Objective: Secondary objectives are to assess the safety and efficacy of the combination of Masitinib and Isoquercetin in the patients under study by evaluating various parameters related to clinical status. Timepoint(s) of evaluation of this end point: Day 15 SECONDARY OUTCOME: Secondary end point(s): The following endpoints will be assessed at day 8 and day 29:; • Clinical status of patients on the 7‐point ordinal scale.; ; The following endpoints will be assessed at day 8, day 15 and day 29:; • Increase in improvement in clinical status of patients (Improvement is defined as score 1 or 2 for moderate COVID‐19 patients and 1, or 2 or 3 for severe COVID‐19 patients); • Reduction of worsening in clinical status of patients (Worsening is defined as score 5 or 6 or 7 for moderate COVID‐19 patients and 6 or 7 for severe COVID‐19 patients); • Time to improvement of two categories in clinical status of patients or discharge (Improvement is defined as score 1 or 2 for moderate COVID‐19 patients and 1, or 2 or 3 for severe COVID‐19 patients); • Time to worsening of two categories in clinical status of patients or need of ICU (Worsening is defined as score 5 or 6 or 7 for moderate COVID‐19 patients and 6 or 7 for severe COVID‐19 patients); • % of patients with normal 02 saturation ; • % of patients without need of oxygenation; • % of patients discharged; • % of patients who went to Intensive Care Unit (ICU); • % of death; • % of patients negative in viral load ; • Time to reach negative viral load ; • CT scan improvement, stable, and worsening; ; Safety Analysis:; ; • Cumulative incidence of serious adverse events (SAEs) ; • Cumulative incidence of Grade 3 and 4 AEs.; • IMP Discontinuation (for any reason); • Changes in white cell count, haemoglobin, platelets, creatinine, glucose, total bilirubin, ALT, and AST over time.; Timepoint(s) of evaluation of this end point: Up to Day 29 INCLUSION CRITERIA: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Has laboratory‐confirmed SARS‐CoV‐2 infection as determined by PCR, or other commercial or public health assay in any specimen < 72 hours prior to randomization. 2. Hospitalized patients 3. Patients not requiring ICU at admission with moderate and severe pneumopathy according to the OMS Criteria of severity of COVID pneumopathy. Moderate cases i.e. cases meeting all of the following criteria: • Showing fever and respiratory symptoms with radiological findings of pneumonia. • Requiring between 3L/min and 5L/min of oxygen to maintain SpO2 >97% Severe cases i.e. cases meeting any of the following criteria: • Respiratory distress (?30 breaths/ min); • Oxygen saturation=93% at rest in ambient air; or Oxygen saturation =97 % with O2 > 5L/min. • PaO2/FiO2?300mmHg 4. Male or non‐pregnant female adult = 18 and < 80 year