Dasatinib for the Treatment of Moderate and Severe COVID-19

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Symptomatic COVID-19 Infection Laboratory-Confirmed
• Intervention / Treatment: Drug: Placebo Administration; Drug: Dasatinib Anhydrous

Detailed 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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (dasatinib anhydrous); Patients receive dasatinib anhydrous PO QD for 14 days in the absence of disease progression or unacceptable toxicity.	Drug: Dasatinib Anhydrous; Given PO
Placebo Comparator: Arm II (placebo administration); Patients receive placebo PO QD for 14 days in the absence of disease progression or unacceptable toxicity.	Drug: Placebo Administration; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute lymphocyte count	Assessment via standard blood chemistry and metabolic panel	Baseline, during treatment (day 1-14) up to 1 month
CRP (C-reactive protein) level	Assessment via standard blood chemistry and metabolic panel	Baseline, during treatment (day 1-14) up to 1 month
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
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
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)
Duration of hospitalization	Outcome reported as the duration of hospitalization of patients	From baseline up to patient's discharge (up to 1 month)
Remission of respiratory symptoms	Time to invasive mechanical ventilation (if not previously initiated) calculated from baseline to intubation.	Up to 1 month
Remission of respiratory symptoms	Time to definitive extubation calculated from intubation (any time occurred) to extubation in days.	Up to 1 month
Remission of respiratory symptoms	Time to independence from oxygen therapy in days.	Up to 1 month

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ann Mohrbacher, MD, University of Southern California

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2022
• Primary Completion (Anticipated): December 15, 2023
• Study Completion (Anticipated): December 15, 2024

Study Registration Dates

• First Submitted: April 1, 2021
• First Submitted That Met QC Criteria: April 1, 2021
• First Posted (Actual): April 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 10, 2022
• Last Update Submitted That Met QC Criteria: August 5, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Occupational Diseases; COVID-19; Laboratory Infection; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: 0S-20-5 (Other Identifier: USC / Norris Comprehensive Cancer Center); P30CA014089 (U.S. NIH Grant/Contract); NCI-2020-04367 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No