Ruxolitinib to Combat COVID-19

Phase 2

Withdrawn

• Conditions: COVID-19
• Interventions: Drug: Ruxolitinib; Procedure: Peripheral blood draw

• Registration Number: NCT04354714
• Lead Sponsor: Washington University School of Medicine

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-04-16
• Study First Submitted QC: 2020-04-16
• Study First Posted: 2020-04-21
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-19
• Last Update Posted: 2020-05-21
• Study Start: 2020-06-30
• Primary Completion: 2021-07-31
• Study Completion: 2021-12-31

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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)

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ruxolitinib	Peripheral blood draw	-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.
Ruxolitinib	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.

Primary Outcome Measures

Name	Time	Method
Overall survival	Through 28 days

Secondary Outcome Measures

Name	Time	Method
Viral kinetics as measured by virologic failure	Through completion of follow-up (estimated to be 7 months)	-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
Number of adverse events as measured by CTCAE v. 5.0	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 on renal replacement therapy	Through completion of follow-up (estimated to be 7 months)
Proportion of participants with detectable virus	Day 29
Length of hospital 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)