Ruxolitinib to Combat COVID-19

A Pilot Study of Ruxolitinib to Combat COVID-19

The investigators hypothesize that JAK 1/2 inhibition with ruxolitinib, an FDA approved treatment for intermediate or high-risk myelofibrosis, could have a similar effect in patients with severe COVID-19, quelling the immune-hyperactivation, allowing for clearance of the virus and reversal of the disease manifestations.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19
• Intervention / Treatment: Drug: Ruxolitinib; Procedure: Peripheral blood draw

• Study Type: Interventional
• Phase: Phase 2

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:

• A diagnosis of advanced COVID-19 as defined by both of the following:

  • A positive test for SARS-CoV-2 RNA detected by RT-PCR collected from the upper respiratory tract (nasopharyngeal and oropharyngeal swab) and, if possible, the lower respiratory tract (sputum, tracheal aspirate, or bronchoalveolar lavage), analyzed by a CLIA certified lab

  • Critical disease manifested by any of the following:

    • Chest imaging (CT or chest X-ray permitted) with ≥ 50% lung involvement
    • Respiratory failure requiring invasive mechanical ventilation or supplementary oxygen with FiO2 ≥ 50%
    • Shock (defined as mean arterial pressure ≤ 65 mmHg unresponsive to 25ml/kg isotonic intravenous fluid resuscitation and/or requiring vasopressor support

    • Cardiac dysfunction defined by:

      • New global systolic dysfunction with ejection fraction ≤ 40%
      • Takotsubo cardiomyopathy
      • New onset supraventricular or ventricular arrhythmias
      • Plasma troponin I ≥ 0.10 ng/mL in someone without previously documented troponin elevation beyond that level

      • Elevated plasma NT-proBNP in someone without documented prior elevation

        • If Age < 50, NT-proBNP > 450 pg/ml
        • If Age 50-74, NT-proBNP > 900 pg/ml
        • If Age ≥ 74, NT-proBNP > 1800 pg/ml
• Receipt of investigational or off-label agents for COVID-19 (prior or ongoing) does not exclude eligibility.
• Patients who have received autologous or allogeneic stem cell transplant are eligible at the discretion of the investigators.
• 18 years of age or older at the time of study registration

• Adequate hematologic function defined as:

  • absolute neutrophil count ≥ 1000/mm3
  • platelet count ≥ 50,000/mm3 without growth factor or transfusion support for 7 days prior to screening
• Creatinine clearance ≥ 15 mL/minute or receiving renal replacement therapy
• Women of childbearing potential (defined as women with regular menses, women with amenorrhea, women with irregular cycles, women using a contraceptive method that precludes withdrawal bleeding, or women who have had a tubal ligation) are required to have a negative pregnancy test and use two forms of acceptable contraception, including one barrier method, during participation in the study treatment period.
• Male patients (if engaging in reproductive sex with a women of childbearing potential) are required to use two forms of acceptable contraception, including one barrier method, during participation in the study and throughout the evaluation period.
• Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable)

Exclusion Criteria:

• Known allergy or intolerance to ruxolitinib or another JAK inhibitor.
• Known or suspected active viral (including HIV, hepatitis B, and hepatitis C), bacterial, mycobacterial, or fungal infection other than COVID-19. Virologic testing not required unless infection is suspected.
• Pregnant and/or breastfeeding.
• Any uncontrolled intercurrent illness that would put the patient at greater risk or limit compliance with study requirements in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ruxolitinib; -Ruxolitinib is an oral medication that will be given twice daily (BID). Dosing on Days 1 through 3 will be 5 mg BID; dosing on Days 4 through 10 will be 10 mg BID.	Drug: Ruxolitinib; For patients unable to swallow pills, a ruxolitinib suspension will be administered through a nasogastric/orogastric tube; Other Names: Jakafi; Procedure: Peripheral blood draw; -Screening, Day 2, Day 4, Day 8, Day 15, and Day 29

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	Through 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral kinetics as measured by virologic failure	-Defined as increase in viral load of >0.5 log on two consecutive days, or >1 log increase in one day, not in keeping with any baseline trend of rising viral loads during the pre-treatment viral testing	Through completion of follow-up (estimated to be 7 months)
Length of hospital stay		Through completion of follow-up (estimated to be 7 months)
Length of ICU stay		Through completion of follow-up (estimated to be 7 months)
Duration of ventilator use		Through completion of follow-up (estimated to be 7 months)
Duration of vasopressors use		Through completion of follow-up (estimated to be 7 months)
Duration on renal replacement therapy		Through completion of follow-up (estimated to be 7 months)
Number of adverse events as measured by CTCAE v. 5.0		Through completion of follow-up (estimated to be 7 months)
Proportion of participants with detectable virus		Day 5
Proportion of participants with detectable virus		Day 10
Proportion of participants with detectable virus		Day 15
Proportion of participants with detectable virus		Day 29

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Incyte Corporation
• Investigators: Principal Investigator: John DiPersio, M.D., Ph.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): June 30, 2020
• Primary Completion (Anticipated): July 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: April 16, 2020
• First Submitted That Met QC Criteria: April 16, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Actual): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 19, 2020
• Last Verified: May 1, 2020

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; COVID-19
• Other Study ID Numbers: 04-13-20-DiPersio

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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