Masitinib in Patients With Symptomatic Mild to Moderate COVID-19

A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate the Anti-viral Efficacy of Masitinib in Patients With Symptomatic Mild to Moderate COVID-19

The objective of the study is to evaluate the anti-viral efficacy of 3 different dosages of masitinib in patients with symptomatic mild to moderate COVID-19.

The primary objective is to evaluate the virologic efficacy of masitinib plus Best Supportive Care (BSC), with respect to placebo plus BSC in reducing viral shedding of SARS-CoV-2 in patients with symptomatic mild to moderate COVID-19. Patients will be randomized into one of the following treatment groups (all patients will receive BSC): Masitinib 3.0 mg/kg/day for 10 days versus corresponding placebo Masitinib 3.0 mg/kg/day for 2 days then 4.5 mg/kg/day for 8 days versus corresponding placebo Masitinib 3.0 mg/kg/day for 2 days then 4.5 mg/kg/day for 2 days then 6.0 mg/kg/day for 6 days versus corresponding placebo Treatments will be administered for 10 days and patients will be followed for 1 month. The treatment groups will be compared to pooled placebo after unblinding. Regarding Best Supportive Care, for patients with a score of 2 and 3 (ambulatory) on the 10-score WHO clinical progression scale, Best Supportive Care is best available therapy in the country at the choice of the investigator excluding any antiviral treatment whether indirect (Ribavirin, Hydroxychloroquine or Chloroquine) or direct (anti-polymerase or antiprotease, including lopinavir/ritonavir fixed dose combination), other investigational treatments for SARS-CoV-2, plasma from a person who recovered from COVID-19, monoclonal antibody therapies and vaccine. For patients with a score of 4 and 5 (hospitalized) on the 10-score WHO clinical progression scale, Best Supportive Care is dexamethasone.

Masitinib 3.0 mg/kg/day for 10 days versus corresponding placebo (all patients will receive Best Supportive Care)

Masitinib 3.0 mg/kg/day for 2 days then 4.5 mg/kg/day for 8 days versus corresponding placebo (all patients will receive Best Supportive Care)

Masitinib 3.0 mg/kg/day for 2 days then 4.5 mg/kg/day for 2 days then 6.0 mg/kg/day for 6 days versus corresponding placebo (all patients will receive Best Supportive Care)

Placebo arms associated with the three Experimental arms (all patients will receive Best Supportive Care) which will be pooled for analysis

Time to negative RT-qPCR result in all tested samples with no subsequent positive RT-qPCR in any tested samples

Key Inclusion Criteria: - Male or non-pregnant female with: A. Symptomatic ambulatory male or non-pregnant female adult ≥ 18 years of age at time of enrolment with mild COVID-19 with score 2 or 3 of the 10-score WHO clinical progression scale OR B. Hospitalized male or non-pregnant female adult ≥ 18 years of age at time of enrolment with COVID-19 with score 4 or 5 of the 10-score WHO clinical progression scale. Symptoms consistent with COVID-19, as determined by investigator, with onset ≤5 days before randomization Positive test for COVID-19 ≤72 hours prior to randomization Negative test for the IgG anti-SARS-CoV-2 Key Exclusion Criteria: Any use of anti-viral medications up to 7 days before participating in the study Receipt of plasma from a person who recovered from COVID-19 (convalescent plasma) any time before participating in the study Receipt of last recommended dose of a SARS-CoV-2 vaccine up to 30 days before participating in the study Receipt of a monoclonal antibodies up to 30 days before participating in the study. Other protocol-defined inclusion/exclusion criteria may apply

Masitinib is under clinical investigation and has not yet been approved in any sought-after indication by any health authority worldwide. As such, there is no plan for data-sharing at this point in time.

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.