Dasatinib for the Treatment of Moderate and Severe COVID-19

Symptomatic COVID-19 Infection Laboratory-Confirmed Clinical Trial

Official title:

A Phase II Randomized Double-Blind Trial of Dasatinib Modulation of Hyperinflammation in Moderate and Severe Patients With COVID-19

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04830735
• Other study ID #: 0S-20-5
• Secondary ID: NCI-2020-043670S
• Status: Withdrawn
• Phase: Phase 2
• Start date: August 5, 2022
• Est. completion date: December 15, 2024

Study information

• Verified date: August 2022
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial investigates how well dasatinib works in treating patients with moderate and severe COVID-19. Dasatinib is a drug used to treat chronic leukemia which may help reduce the strong inflammation caused by COVID-19 that can damage the lungs or other organs.

Description:

PRIMARY OBJECTIVES:

I. To determine the proportion of patients requiring intubation/ventilator support, requiring rescue with tocilizumab, or dying.

II. To determine 1 month survival.

SECONDARY OBJECTIVES:

I. To estimate the safety and tolerability of dasatinib anhydrous (dasatinib) in the setting of COVID-19 infection.

II. To determine change in C-reactive protein (CRP) levels after starting therapy.

III. To document activity of dasatinib in lessening cytokine release syndrome (CRS) and sequential organ failure assessment (SOFA) score.

EXPLORATORY OBJECTIVES:

I. Interleukin-6 /cytokine assay weekly on treatment protocol. II. Ferritin levels at study entry and every (q) 2 days on treatment protocol. III. D-dimer levels at study entry and q 2 days on treatment protocol.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive dasatinib anhydrous orally (PO) once daily (QD) for 14 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO QD for 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 28 days.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 15, 2024
• Est. primary completion date: December 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have laboratory test proven COVID19 and symptomatic disease requiring hospitalization: virological diagnosis of Sars-CoV2 infection (polymerase chain reaction [PCR]) within 14 days

• Able to sign informed consent for participation in the study

• Subject is hospitalized with one or more of the following:

• Moderate disease: peripheral capillary oxygen saturation (SpO2) >= 93% on room air with one of the following risk factors for developing severe disease: age >= 60 years, history of hypertension, diabetes mellitus, cardiac disease, chronic lung disease, obesity (calculated body mass index [BMI] >= 30 kg/m^2), and cardiovascular disease, clinical and/or radiological evidence of chest involvement, CRP > 2X upper limit of normal, doubling of CRP in 24 hours where chest findings and CRP elevation not explained by other underlying disease.

After the first interim analysis, we may allow enrollment of severe disease COVID infected patients if safety and efficacy analysis appears favorable:

• Severe disease:

• Respiratory rate >= 30 breaths/ minute (min)

• SpO2 < 93% while breathing room air

• Partial pressure of oxygen measurement (PaO2)/fraction of inspired oxygen (FiO2) =< 300 mmHg

• Absolute neutrophil count (ANC) > 1000 (baseline blood counts)

• Platelets > 50,000 / mmc (baseline blood counts)

• Alanine aminotransferase/aspartate aminotransferase (ALT/AST) < 5 times the upper limit of the normality

• Total bilirubin < 3 x institutional upper limit of normal (IULN)

• Creatinine < 2.5 times the upper limit of the normality

• Azithromycin allowed but if on both drugs patient should be on constant cardiovascular (CV) monitoring

• Subject must understand and voluntarily sign an informed consent form (ICF) prior to any study-related assessment/procedures being conducted

• Subject is willing and able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

• Pleural effusion > grade 2 evident on chest x-ray (CXR) or chest computed tomography (CT)

• Intubation/mechanical ventilation

• Known hypersensitivity to dasatinib

• Patient being treated with immunomodulators or anti-rejection drugs

• Known active infections or other clinical condition that contraindicate dasatinib and cannot be treated or solved according to the judgement of the clinician

• ALT/AST > 5 times the upper limit of the normality

• Total bilirubin > 3 x IULN

• Neutrophils < 1000 / mmc unless; platelets < 50,000 / mmc

Related Conditions & MeSH terms

• COVID-19
• Symptomatic COVID-19 Infection Laboratory-Confirmed

Intervention

Drug:
• Dasatinib Anhydrous
Given PO
• Placebo Administration
Given PO

Locations

Country	Name	City	State
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of Southern California	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants requiring invasive mechanical ventilation, requiring tocilizumab or dying	Outcome reported as the number of patients requiring mechanical ventilation, requiring tocilizumab or dying.	Up to 28 days
Secondary	Absolute lymphocyte count	Assessment via standard blood chemistry and metabolic panel	Baseline, during treatment (day 1-14) up to 1 month
Secondary	CRP (C-reactive protein) level	Assessment via standard blood chemistry and metabolic panel	Baseline, during treatment (day 1-14) up to 1 month
Secondary	Change of the SOFA (Sequential Organ Failure Assessment)	The SOFA score assessment will be based on PaO2/FiO2, platelets, Glasgow coma scale (GCS), bilirubin, Mean arterial pressure OR administration of vasoactive agents required, and Serum creatinine	Baseline, during treatment (day 1-14) up to 1 month
Secondary	Number of participants with treatment-related side effects	Outcome reported as the number of adverse events and serious adverse events that occurred.	During treatment and up to 30 days after the last treatment dose
Secondary	Radiological response	Will be evaluated by chest x-ray or pulmonary computed tomography (CT)	Baseline (optional), after seven days and if clinically indicated(up to 1 month)
Secondary	Duration of hospitalization	Outcome reported as the duration of hospitalization of patients	From baseline up to patient's discharge (up to 1 month)
Secondary	Remission of respiratory symptoms	Time to invasive mechanical ventilation (if not previously initiated) calculated from baseline to intubation.	Up to 1 month
Secondary	Remission of respiratory symptoms	Time to definitive extubation calculated from intubation (any time occurred) to extubation in days.	Up to 1 month
Secondary	Remission of respiratory symptoms	Time to independence from oxygen therapy in days.	Up to 1 month