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Ruxolitinib for Treatment of Covid-19 Induced Lung Injury ARDS (RuXoCoil)

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ClinicalTrials.gov Identifier: NCT04359290
Recruitment Status : Active, not recruiting
First Posted : April 24, 2020
Last Update Posted : December 1, 2020
Sponsor:
Information provided by (Responsible Party):
Philipps University Marburg Medical Center

Study Description
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Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of patients with COVID-19 severe pneumonia.

Condition or disease Intervention/treatment Phase
ARDS, Human COVID Drug: Ruxolitinib administration Phase 2

Detailed Description:

This clinical trial is an open-label trial of ruxolitinib for the treatment of severe COVID-19 to assess its efficacy and safety.

Ruxolitinib (INCB018424 phosphate, INC424, ruxolitinib phosphate) is a well established, potent and selective inhibitor of Janus kinase (JAK)1 and JAK2, with modest to marked selectivity against tyrosine kinase (TYK)2 and JAK3, respectively. Ruxolitinib interferes with the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function.

Ruxolitinib (JAKAVI®) is currently approved in the European Union (EU) for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (PMF) (also known as chronic idiopathic MF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET-MF) and for the treatment of adult patients with PV who are resistant to or intolerant of hydroxyurea (HU). In the US, ruxolitinib has been approved in the treatment of steroid refractory graft versus host disease post allogeneic stem cell transplantation.

Because many patients with severe respiratory disease due to COVID-19 have features consistent with the cytokine release syndrome (CRS) and increased activation of the JAK/STAT pathway, it is postulated that ruxolitinib might have a useful role in treating these patients.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Ruxolitinib will be administered p.o. or by gavage feeding starting with 2 x 10mg or 2 x 15mg bid dose at day 1 according to the investigator's decision and can be increased up to 2 x 15mg bid from day 2 to day 28 (max) (depending on platelet counts and renal function). Ruxolitinib will be administered in the morning and evening. Dosing will be adjusted according to toxicity and kidney function; open design, single arm.If the patient is discharged before day 28, the therapy will be discontinued for discharge.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Ruxolitinib for Treatment of Covid-19 Induced Lung Injury ARDS A Single-arm, Open-label, Proof of Concept Study
Actual Study Start Date : July 1, 2020
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : July 2021

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Ruxolitinib treatment
Ruxolitinib will be administered p.o. or by gavage feeding for max 28 days
 Drug: Ruxolitinib administration
Ruxolitinib will be administered p.o. or by gavage feeding starting with 2 x 10mg or 2 x 15mg bid dose at day 1 according to the investigator's decision and can be increased up to 2 x 15mg bid from day 2 to day 28 (max) (depending on platelet counts and renal function). Ruxolitinib will be administered in the morning and evening. Dosing will be adjusted according to toxicity and kidney function.If the patient is discharged before day 28, the therapy will be discontinued for discharge.


Outcome Measures
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Primary Outcome Measures :
  1. Overall survival [ Time Frame: 28 days after registration into trial ]
    To determine the efficacy of ruxolitinib measured by overall survival


Secondary Outcome Measures :
  1. Assessment of the duration of ventilation support [ Time Frame: registration until 90 days after registration into trial ]
    Assessment of the duration of ventilation support

  2. cytokine storm [ Time Frame: registration until 90 days after registration into trial ]
    Assessment of the extent of cytokine storm reduction (IL-6, CRP, ferritin)

  3. time on ICU [ Time Frame: registration until 90 days after registration into trial ]
    To assess time on ICU

  4. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: registration until 90 days after registration into trial ]
    In order to classify the severity of the AEs, number of participants with treatment-related adverse events will be assessed by the "Common Terminology Criteria for Adverse Events" (CTCAE) version 5.0

  5. time frame for seroconversion under ruxolitinib treatment (SARS-Co-19- IgG) [ Time Frame: registration until 90 days after registration into trial ]
    To assess the timeframe for seroconversion under ruxolitinib treatment (SARS-Co-19- IgG)

  6. Rates of flow [ Time Frame: Discharge from hospital (end of treatment) ]
    To asses the rates of flow (liter/minute), in order to detect possible amelioration of pulmonary function after Covid-19 infection

  7. Gas exchange [ Time Frame: Discharge from hospital (end of treatment) ]
    To asses gas exchange (partial pressure of oxygen and carbon dioxide), in order to detect possible amelioration of pulmonary function after Covid-19 infection

  8. Forced expiratory volume in 1 second (FEV1) [ Time Frame: Discharge from hospital (end of treatment) ]
    To assess forced expiratory volume in 1 second (liters), in order to detect possible possible amelioration of pulmonary function after Covid-19 infection

  9. Forced vital capacity (FVC) [ Time Frame: Discharge from hospital (end of treatment) ]
    To assess forced vital capacity (liters), in order to detect possible possible amelioration of pulmonary function after Covid-19 infection

  10. Tiffeneau-Pinelli index [ Time Frame: Discharge from hospital (end of treatment) ]
    To assess Tiffeneau-Pinelli index (FEV1/FVC ratio in %), in order to detect possible possible amelioration of pulmonary function after Covid-19 infection

  11. Overall survival [ Time Frame: 90 days after registration into trial ]
    To determine the efficacy of ruxolitinib measured by overall survival


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or non-pregnant female adult ≥18 years of age at time of enrollment.
  2. has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay (result of the PCR is not necessary for inclusion, but has to approved latest within 48-72 hours after registration)
  3. Willingness of men and women of childbearing potential to use highly effective contraceptive methods by abstinence or by using at least two contraceptive methods from the date of consent to the end of the study

  4. severe lung disease as defined by following:

    1. Recent intubation
    2. Requirement of invasive ventilation moderate to severe pulmonary oxygen exchange disturbance as defined by (PaO2/FiO2) ≤ 200 mmHg at a PEEP ≥ 5mm H2O
    3. Serum LDH > 283 U/l
    4. Ferritin above normal value
    5. CT-scan: pulmonary infiltration compatible with Covid-19 disease
  5. Patient or patient´s representative must provide written informed consent (and assent if applicable) before any study assessment is performed.

Exclusion Criteria:

  1. Uncontrolled HIV infection
  2. Active tuberculosis (result of positive tuberculosis infection is not necessary for exclusion, but has to approved later on during patient´s intervention)
  3. Chronic kidney disease requiring dialysis
  4. ALT/AST > 5 times the upper limit of normal.
  5. Pregnancy or breast feeding.
  6. Allergy to study medication
  7. Simultaneous participation in another clinical trial with an experimental treatment
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04359290


Locations
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Germany
Andreas Neubauer
Marburg, Germany, D-35043
Sponsors and Collaborators
Philipps University Marburg Medical Center
Investigators
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Principal Investigator: Andreas Neubauer, Prof Dr. Universitätsklinikum Giessen und Marburg (UKGM)
More Information
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Publications:
[WHO] World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected [Resource on the internet]. 2020 [updated 13 March 2020; cited 24 March 2020]. Available from: https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected
An Insight of comparison between COVID-19 (2019-nCoV disease) and SARS in pathology and pathogenesis. Author: Xiaolong Cai; Internet posting, of 27-Feb-2020 retrieved 24-Mar-2020. Cite as DOI: 10.31219/osf.io/hw34x
Ruxolitinib Prevents Cytokine Release Syndrome after CART Cell Therapy without Impairing the Anti-Tumor Effect in a Xenograft Model Saad S Kenderian, MD , Blood (2016) 128 (22): 652
The definition and risks of Cytokine Release Syndrome-Like in 11 COVID-19-Infected Pneumonia critically ill patients: Disease Characteristics and Retrospective Analysis Wenjun Wang Jr. et al Internet posting of 27-Feb-2020 retrieved 24-Mar-2020 Cite as: https://doi.org/10.1101/2020.02.26.20026989

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Responsible Party: Philipps University Marburg Medical Center
ClinicalTrials.gov Identifier: NCT04359290    
Other Study ID Numbers: KKS-278
First Posted: April 24, 2020    Key Record Dates
Last Update Posted: December 1, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Study protocol will be provided after publication
Supporting Materials: Study Protocol
Time Frame: 3 Months after publication
Access Criteria: Central server

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Philipps University Marburg Medical Center:
Covid-19
ARDS
Ruxolitinib
 Janus kinase
JAK1
JAK2
Additional relevant MeSH terms:
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Lung Injury
Respiratory Distress Syndrome, Adult
Lung Diseases
Respiratory Tract Diseases
 Thoracic Injuries
Wounds and Injuries
Respiration Disorders