Dasatinib for the Treatment of Moderate and Severe COVID-19

NCT ID: NCT04830735

Last Updated: 2022-08-10

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-05
• Study Completion Date: 2024-12-15

Brief 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.

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.

Conditions

Symptomatic COVID-19 Infection Laboratory-Confirmed

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm I (dasatinib anhydrous)

Patients receive dasatinib anhydrous PO QD for 14 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Dasatinib Anhydrous

Intervention Type: DRUG

Given PO

Arm II (placebo administration)

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

Group Type: PLACEBO_COMPARATOR

Placebo Administration

Intervention Type: DRUG

Given PO

Interventions

Dasatinib Anhydrous

Given PO

Intervention Type: DRUG

Placebo Administration

Given PO

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Southern California

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ann Mohrbacher, MD

Role: PRINCIPAL_INVESTIGATOR

University of Southern California

Locations

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Countries

United States

Other Identifiers

NCI-2020-04367

Identifier Type: REGISTRY

Identifier Source: secondary_id

0S-20-5

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA014089

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0S-20-5

Identifier Type: -

Identifier Source: org_study_id