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Dasatinib for the Treatment of Moderate and Severe COVID-19

Primary Purpose

Symptomatic COVID-19 Infection Laboratory-Confirmed

Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dasatinib Anhydrous
Placebo Administration
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Symptomatic COVID-19 Infection Laboratory-Confirmed

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • USC / Norris Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (dasatinib anhydrous)

Arm II (placebo administration)

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Absolute lymphocyte count
Assessment via standard blood chemistry and metabolic panel
CRP (C-reactive protein) level
Assessment via standard blood chemistry and metabolic panel
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
Number of participants with treatment-related side effects
Outcome reported as the number of adverse events and serious adverse events that occurred.
Radiological response
Will be evaluated by chest x-ray or pulmonary computed tomography (CT)
Duration of hospitalization
Outcome reported as the duration of hospitalization of patients
Remission of respiratory symptoms
Time to invasive mechanical ventilation (if not previously initiated) calculated from baseline to intubation.
Remission of respiratory symptoms
Time to definitive extubation calculated from intubation (any time occurred) to extubation in days.
Remission of respiratory symptoms
Time to independence from oxygen therapy in days.

Full Information

First Posted
April 1, 2021
Last Updated
August 5, 2022
Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04830735
Brief Title
Dasatinib for the Treatment of Moderate and Severe COVID-19
Official Title
A Phase II Randomized Double-Blind Trial of Dasatinib Modulation of Hyperinflammation in Moderate and Severe Patients With COVID-19
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Withdrawn
Why Stopped
PI decided not to pursue study
Study Start Date
August 5, 2022 (Actual)
Primary Completion Date
December 15, 2023 (Anticipated)
Study Completion Date
December 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Symptomatic COVID-19 Infection Laboratory-Confirmed

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (dasatinib anhydrous)
Arm Type
Experimental
Arm Description
Patients receive dasatinib anhydrous PO QD for 14 days in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm II (placebo administration)
Arm Type
Placebo Comparator
Arm Description
Patients receive placebo PO QD for 14 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Dasatinib Anhydrous
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Placebo Administration
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Proportion of participants requiring invasive mechanical ventilation, requiring tocilizumab or dying
Description
Outcome reported as the number of patients requiring mechanical ventilation, requiring tocilizumab or dying.
Time Frame
Up to 28 days
Secondary Outcome Measure Information:
Title
Absolute lymphocyte count
Description
Assessment via standard blood chemistry and metabolic panel
Time Frame
Baseline, during treatment (day 1-14) up to 1 month
Title
CRP (C-reactive protein) level
Description
Assessment via standard blood chemistry and metabolic panel
Time Frame
Baseline, during treatment (day 1-14) up to 1 month
Title
Change of the SOFA (Sequential Organ Failure Assessment)
Description
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
Time Frame
Baseline, during treatment (day 1-14) up to 1 month
Title
Number of participants with treatment-related side effects
Description
Outcome reported as the number of adverse events and serious adverse events that occurred.
Time Frame
During treatment and up to 30 days after the last treatment dose
Title
Radiological response
Description
Will be evaluated by chest x-ray or pulmonary computed tomography (CT)
Time Frame
Baseline (optional), after seven days and if clinically indicated(up to 1 month)
Title
Duration of hospitalization
Description
Outcome reported as the duration of hospitalization of patients
Time Frame
From baseline up to patient's discharge (up to 1 month)
Title
Remission of respiratory symptoms
Description
Time to invasive mechanical ventilation (if not previously initiated) calculated from baseline to intubation.
Time Frame
Up to 1 month
Title
Remission of respiratory symptoms
Description
Time to definitive extubation calculated from intubation (any time occurred) to extubation in days.
Time Frame
Up to 1 month
Title
Remission of respiratory symptoms
Description
Time to independence from oxygen therapy in days.
Time Frame
Up to 1 month

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ann Mohrbacher, MD
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
USC / Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Dasatinib for the Treatment of Moderate and Severe COVID-19

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