Official Title
Preliminary Clinical Study of Efficacy and Safety of Flunotinib Maleate Tablets Combined With Antiviral Therapy in Patients With Severe Novel Coronavirus (COVID-19) Infection
Brief Summary

Flonoltinib Maleate as a JAK/FLT3 dual target inhibitor, previous pharmacologicalexperiments showed that the IC50 inhibition of JAK2 kinase was as low as 0.8 nM, whilethe IC50 inhibition of JAK1, JAK3 and TYK2 kinases was 26 nM, 39 nM and 2 nM,respectively, and the IC50 of FLT3 kinase was 15 nM. It has high inhibitory activity forJAK2 kinase and good selectivity for JAK family.Multiple pharmacodynamic modelsevaluating the anti-inflammatory effect of Flonoltinib Maleate showed that FlonoltinibMaleate showed better therapeutic effect than the clinical drug Ruxolitinib with lowertoxicity.

Detailed Description

Not Provided

Active, not recruiting
COVID-19

Drug: SOC

In this study, the standard treatment plan (SOC) for COVID-19 in the Department of
Respiratory and Critical Care Medicine was used as the best accessible treatment, and the
treatment plan principle was based on the latest national guidance document ("Expert
Recommendations for Clinical Treatment of Severe Novel Coronavirus Infection Caused by
Omicron Variant"; "Diagnosis and Treatment Plan for Novel Coronavirus Infection (Trial
Version 10)"; "Diagnosis and Treatment Plan for Severe Cases of Novel Coronavirus
Infection (Trial Fourth Edition)"). In this study, the drug flunotinib maleate (FM) 100mg
is a class of JAK inhibitors of anti-inflammatory therapy of SOC as standard clinical
treatment regimen, and will be used in combination with SOC according to the judgment of
the investigator.

Eligibility Criteria

Inclusion Criteria:

1. Age≥ 18 years old, gender is not limited;

2. COVID-19 infection inclusion criteria: hospitalized with coronavirus (COVID-19)
within 14 days, samples collected 72 hours before enrollment confirmed by polymerase
chain reaction (PCR) test or antigen test (if due to lack of testing supplies,
testing capacity and conditions are limited, but indicate a progressive disease with
persistent infection with COVID-19), the investigator judged that the condition was
aggravated, and any of the following criteria were met as severe COVID-19 patients:

Respiratory distress, respiratory rate≥ 30 times/min; At rest, oxygen saturation ≤
93% when inhaling air; Arterial partial pressure of oxygen (PaO2)/oxygen inhalation
concentration (FiO2)≤ 300 mmHg; Clinical symptoms are progressively aggravated, lung
imaging shows that the lesions within 24~48h have progressed significantly > 50%.

Adults with any of the following are defined as critically ill with COVID-19:
respiratory failure requiring mechanical ventilation; Appearance of shock; Other
organ failure requires ICU monitoring; Severe and critical cases of novel
coronavirus infection, collectively referred to as "severe cases". Severe cases can
also be managed as severe cases if pneumonia caused by novel coronavirus infection
does not meet the diagnostic criteria for severe cases: age > 65 years old,
incomplete full vaccination, and more serious chronic diseases (including
hypertension, diabetes, coronary heart disease, chronic lung disease, malignant
tumors, and immunocompromise, etc.)

3. Patients with risk of progression before enrollment: at least one inflammatory index
greater than the upper limit of normal (IL-6, CRP, d-dimer, LDH, ferritin≥ULN)
within 2 days;

4. willing and/or able to comply with research-related procedures and assessments;

5. Those who can understand and agree to participate in this research and sign the
informed consent form;

Exclusion Criteria:

1. Known or suspected allergy to the test drug and its excipients;

2. Are receiving cytotoxic or biological therapy (such as TNF inhibitors, IL-1
inhibitors, IL-6 inhibitors (tocilizumab, adalimumab, etc.), T cell or B cell
targeted therapy (rituximab, interferon, etc.), or Janus kinase (JAK) inhibitors,
except for this study.

3. Have received convalescent new coronary pneumonia plasma or intravenous human
immunoglobulin; have received clearly effective COVID-19 virus neutralizing
antibodies;

4. In addition to the new crown infection, there are other serious infections,
suspected serious bacteria, fungal viruses, active tuberculosis, NTM, etc.

5. Known positive for HIV antibody, positive test for active hepatitis B virus (HBsAg
positive, HBV-DNA positive or ≥1000 copies/mL), anti-HCV antibody or HCV-RNA
positive;

6. Have received a live vaccine within 1 week prior to screening, or are expected to be
vaccinated during the study period.

7. Severe liver disease (total bilirubin (TBIL) ≥ 3 times the upper limit of normal
value, alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥5 times the
upper limit of normal value);

8. Those with severe renal insufficiency (glomerular filtration rate ≤ 30 mL/min/1.73
m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal
dialysis;

9. Blood routine: neutrophil count < 1.0×109/L, lymphocyte count < 0.2×109/L, platelet
< 30×109/L, hemoglobin < 60g/L;

10. Patients with malabsorption syndrome, or any other condition that affects
gastrointestinal absorption, requiring intravenous nutrition or unable to take oral
medications;

11. Invasive respiratory support or advanced life support, such as ECMO, is required.

Patients who have suffered from malignant tumors in the past 5 years and are currently
uncontrolled; (13) Patients who participated in other new drugs or medical devices within
1 month before screening and took the investigational drug and used the investigational
device; (14) Pregnant or lactating female patients, female patients with fertility and
male patients who refuse to use contraception during the trial and within 6 months after
the end of the test; (15) having taken a strong CYP3A inhibitor (such as ketoconazole,
clarithromycin, itraconazole) or a strong CYP3A4 inducer (rifampicin) within two weeks
before the first dose; (16) Patients with congenital coagulation abnormalities, such as
patients with a history of multiple thrombosis and bleeding diseases; (17) Alcohol
dependence or drug abuse; The researchers believe that patients with rapid disease
progression are unlikely to survive for at least 48 hours after screening; or other
factors that are not suitable for participation in the trial。

Eligibility Gender
All
Eligibility Age
Minimum: 18 Years ~ Maximum: N/A
Countries
China
Locations

Chengdu Zenitar Biomedical Technology Co., Ltd
Chengdu, Sichuan, China

Not Provided

Chengdu Zenitar Biomedical Technology Co., Ltd
NCT Number
MeSH Terms
COVID-19