Masitinib Combined With Isoquercetin and Best Supportive Care in Hospitalized Patients With Moderate and Severe COVID-19

Study Overview
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Brief Summary
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Study objective is to evaluate the efficacy of the combination of masitinib and isoquercetin in adult hospitalized patients with moderate and severe COVID-19.

Detailed Description
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COVID-19 is a respiratory disease caused by a novel coronavirus (SARS-CoV-2) that is associated with substantial morbidity and mortality. There is currently no vaccine to prevent COVID-19 or infection with SARS-CoV-2 or therapeutic agent to treat COVID-19. Many patients with moderate and severe COVID-19, develop a cytokine storm that leads to severe pulmonary inflammation and various thrombotic events associated with acute respiratory distress syndrome (ARDS) and potentially death. The combination of masitinib and isoquercetin may prevent the development of these two complications. Masitinib is a potent blocker of mast cells and macrophages that are contributors to the cytokine storm. Isoquercetin inhibits disulfide isomerase (PDI), an enzyme directly involved in the formation of clots, and also decreases D-Dimer, a predictor of COVID-19 thrombosis severity. The primary objective of this study is to evaluate efficacy of the masitinib and isoquercetin combination in moderate and severe COVID-19 patients. The primary endpoint is subject clinical status at day 15, using a 7-point ordinal scale that is defined as follows: 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.

Official Title
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Randomized, Phase 2 Clinical Trial to Evaluate the Safety and Efficacy of Masitinib Combined With Isoquercetin, and Best Supportive Care in Hospitalized Patients With Moderate and Severe COVID-19

Conditions
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SARS-CoV 2, COVID-19, Coronavirus Disease 2019

Intervention / Treatment
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* Drug: Masitinib
* Drug: Isoquercetin
* Drug: Best Supportive Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has laboratory-confirmed SARS-CoV-2 infection Hospitalized patients for the treatment of COVID pneumopathy Patients not requiring ICU at admission with moderate and severe pneumopathy according to the OMS Criteria of severity of COVID pneumopathy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Masitinib plus Isoquercetin plus Best Supportive Care<br>Patients will receive oral masitinib dose of 3 mg/kg/day for 4 days then 4.5 mg/kg/day. The dose of isoquercetin will be 1 g/day by oral route. Best Supportive Care is best available therapy at the choice of the investigator, including, but not limited to, oxygenation, analgesics, anti-thrombotics, anti-viral drugs, or biologics drugs. | Drug: Masitinib<br>* Masitinib is a small molecule drug that selectively inhibits specific tyrosine kinases such as colony-stimulating factor 1 receptor (CSF1R), c-Kit, LYN, FYN, and platelet-derived growth factor receptor (PDGFR) α and β, in the submicromolar range.<br>* Other names: AB1010;Drug: Isoquercetin<br>* Isoquercetin is a flavonoid, derivative of quercetin. Isoquercetin is rapidly hydrolyzed to quercetin.<br>* Other names: isotrifoliin;Drug: Best Supportive Care<br>* Best Supportive Care is best available therapy at the choice of the investigator, including, but not limited to, oxygenation, analgesics, anti-thrombotics, anti-viral drugs or biologics drugs.<br>* Other names: BSC;|
| Active Comparator: Best Supportive Care<br>Best Supportive Care is best available therapy at the choice of the investigator, including, but not limited to, oxygenation, analgesics, anti-thrombotics, anti-viral drugs, or biologics drugs. | Drug: Best Supportive Care<br>* Best Supportive Care is best available therapy at the choice of the investigator, including, but not limited to, oxygenation, analgesics, anti-thrombotics, anti-viral drugs or biologics drugs.<br>* Other names: BSC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical status of patients at day-15 using a 7-point ordinal scale | Ordinal scale defined as follows: 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. | 15 days |