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

NCT ID: NCT04622865

Last Updated: 2023-02-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-06-01

Study Completion Date

2023-12-31

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.

Conditions

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SARS-CoV 2 COVID-19 Coronavirus Disease 2019

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Masitinib plus Isoquercetin plus Best Supportive Care

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.

Group Type EXPERIMENTAL

Masitinib

Intervention Type DRUG

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.

Isoquercetin

Intervention Type DRUG

Isoquercetin is a flavonoid, derivative of quercetin. Isoquercetin is rapidly hydrolyzed to quercetin.

Best Supportive Care

Intervention Type DRUG

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.

Best Supportive Care

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.

Group Type ACTIVE_COMPARATOR

Best Supportive Care

Intervention Type DRUG

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.

Interventions

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Masitinib

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.

Intervention Type DRUG

Isoquercetin

Isoquercetin is a flavonoid, derivative of quercetin. Isoquercetin is rapidly hydrolyzed to quercetin.

Intervention Type DRUG

Best Supportive Care

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.

Intervention Type DRUG

Other Intervention Names

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AB1010 quercetin-3-O-glucoside isotrifoliin BSC

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AB Science

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pascal Chanez, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Respiratory Diseases, Aix-Marseille University, Marseille, France

Locations

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Centre Hospitalier du Pays d'Aix

Aix-en-Provence, , France

Site Status RECRUITING

Le Tripode, Groupe hospitalier Pellegrin CHU de Bordeaux

Bordeaux, , France

Site Status RECRUITING

CHU Clermont-Ferrand: Site Gabriel-Montpied

Clermont-Ferrand, , France

Site Status RECRUITING

Hopital Nord, AP-HM

Marseille, , France

Site Status RECRUITING

CHR Orleans, Hopital de la Source

Orléans, , France

Site Status RECRUITING

Hopital Larrey, CHU du Toulouse

Toulouse, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Clinical Study Coordinator

Role: CONTACT

+33(0)147200014

References

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Durojaye OA, Okoro NO, Odiba AS, Nwanguma BC. MasitinibL shows promise as a drug-like analog of masitinib that elicits comparable SARS-Cov-2 3CLpro inhibition with low kinase preference. Sci Rep. 2023 Apr 28;13(1):6972. doi: 10.1038/s41598-023-33024-2.

Reference Type DERIVED
PMID: 37117213 (View on PubMed)

Latham BD, Oskin DS, Crouch RD, Vergne MJ, Jackson KD. Cytochromes P450 2C8 and 3A Catalyze the Metabolic Activation of the Tyrosine Kinase Inhibitor Masitinib. Chem Res Toxicol. 2022 Sep 19;35(9):1467-1481. doi: 10.1021/acs.chemrestox.2c00057. Epub 2022 Sep 1.

Reference Type DERIVED
PMID: 36048877 (View on PubMed)

Other Identifiers

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2020-001635-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AB20001

Identifier Type: -

Identifier Source: org_study_id

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