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Ruxolitinib in the Treatment of Covid-19

Primary Purpose

COVID-19

Status

Unknown status

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

INC424 / Ruxolitinib

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring Ruxolitinib, Covid-19, SARS

Eligibility Criteria

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

Inclusion Criteria:

Patients ≥ 18 years.
SARS-Cov2 infection confirmed by a validated method.
Presence of COVID-19 severe acute respiratory syndrome with:
Respiratory rate ≥ 20/min O2 saturation ≤93% with FiO2 of 0.21 Lung images by means of computerized tomography or thorax radiography compatible with respiratory involvement due to COVID-19.
Signed informed consent.

Exclusion Criteria:

Pregnancy or breast-feeding.
Platelets < 50,000/mm3.
Neutrophils < 1,000/mm3.
Hemoglobin < 6 g/dl
Creatinine ≥2 mg/dl or creatinine clearance ≤30 ml/min.
Total serum bilirubin > 2.0 x upper limit of normal and/or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times the upper limit of normal.
Known active infection due to HIV, HVC, HVB, Herpes Zoster or Micob Tuberculosis
Treatment with Tocilizumab, Baricitinib or Interferon.
History of hypersensitivity to ruxolitinib or to any medicine with similar chemical compounds
Patients with mechanical respiratory assistance
Patients under treatment with Ruxolitinib due to hematological disease
Any condition that, according to the Investigator, may interfere with the complete participation of the patient in the study, including the administration of the medicinal product, the limitation of visits, the implication of a risk for the patient or that prevents the correct interpretation of the results.

Treatment Suspension Criteria

Voluntary decision of the patient
Treating physician's decision to discontinue the treatment
Drug toxicity grade 3 or higher (CTCAE 5.0).

Study Design

Experimental, open-label, prospective, single center, add-on (added to the standard treatment) study, compared with the historical control arm.

Control arm: It will include patients with COVID-19 Respiratory Syndrome who meet the aforementioned selection criteria and have received the standard of care (SOC). Efforts will be made so that both arms share similar demographic characteristics as regards gender and age group. Ten centers will participate, which will share the same protocol and their results may be jointly analyzed. The expected n per center is 10-15 patients.

For the safety assessment as part of the objective, the following parameters will be taken into account:

Biochemical changes: (day 1, 8 and 14) Leukocytes, Formula, Hemoglobin, platelets, creatinine, glycemia, PT, Bilirubin, GOT/GPT.
Grade 3/4 Toxicity, SAE (Serious Adverse Event)
Incidence of discontinuation, suspension or dose-reduction of the study drug.
Incidence of secondary infections.

Efficacy Assessment:

Efficacy will be graded according to the ordinal scale of 8 points.
Time to Improvement
Time of response consolidation
Changes in NEWS table

Sites / Locations

Outcomes

Primary Outcome Measures

Evaluate the efficacy of ruxolitinib in the treatment of COVID-19 severe acute respiratory syndrome

Measuring the proportion of patients with clinical worsening (defined by a requirement of FIO2 >50% and/or mechanical respiratory assistance)

Secondary Outcome Measures

Evaluate the median duration of hospitalization.

Evaluate the evolution of systemic inflammation parameters.

Evaluation at the beginning (baseline), middle and end of the treatment with ruxolitinib of PCR, LDH, ESD, Ferritin and IL-6 (if available).

Evaluate COVID-19 mortality rate

Evaluate the proportion of the requirement of mechanical ventilation.

Evaluate ruxolitinib adverse reactions

Evaluate the proportion of secondary infections during the treatment with ruxolitinib

Full Information

NCT ID

NCT04414098

First Posted

May 29, 2020

Last Updated

June 1, 2020

Sponsor

Marcelo Iastrebner

Collaborators

Novartis

1. Study Identification

Unique Protocol Identification Number

NCT04414098

Brief Title

Ruxolitinib in the Treatment of Covid-19

Official Title

Safety and Efficacy Study of Ruxolitinib in the Treatment of Severe Acute Respiratory Syndrome Due to SARS-COV-2

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Unknown status

Study Start Date

June 1, 2020 (Anticipated)

Primary Completion Date

August 15, 2020 (Anticipated)

Study Completion Date

September 15, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Marcelo Iastrebner

Collaborators

Novartis

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

The treatment of COVID-19 severe acute respiratory syndrome with ruxolitinib 5 mg orally every 12 hours during 14 days would stop the disproportionate inflammatory response, causing a reduction in the proportion of patients who show a progression and worsening of the severe acute respiratory syndrome.

Detailed Description

Primary Objective Evaluate the efficacy of ruxolitinib in the treatment of COVID-19 severe acute respiratory syndrome by means of measuring the proportion of patients with clinical worsening (defined by a requirement of FIO2 50% and/or mechanical respiratory assistance) during 14 days after the commencement of treatment. Secondary Objectives Evaluate the median duration of hospitalization. Median duration after 45 days of commencement of treatment. Evaluate the evolution of systemic inflammation parameters. Evaluation at the beginning (baseline), middle and end of the treatment with ruxolitinib of PCR, LDH, ESD, Ferritin and IL-6. Evaluate COVID-19 mortality rate after 45 days of treatment. Evaluate the proportion of the requirement of mechanical ventilation. Evaluate ruxolitinib adverse reactions with a total follow-up of 45 days. Evaluate the proportion of secondary infections during the treatment with ruxolitinib.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19

Keywords

Ruxolitinib, Covid-19, SARS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Experimental, open-label, prospective, single center, add-on (added to the standard treatment) study, compared with an historical control arm.

Masking

None (Open Label)

Allocation

N/A

Enrollment

100 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

INC424 / Ruxolitinib

Other Intervention Name(s)

Jakavi

Intervention Description

Ruxolitinib 5 mg orally every 12 hours during 14 days. Total Follow-up time will be of 45 days. The reduction of ruxolitinib dose will be considered in cases of drug-related cytopenias. During hospitalization, clinical and laboratory evolution parameters will be recorded daily in the medical history of the patient and in the data collection table of the study. Upon patient's discharge, a follow-up will be conducted until day +45 During hospitalization, adverse events will be monitored daily by means of clinical assessment and laboratory data. After discharge, monitoring of adverse events will continue during the outpatient follow-up. Pro-inflammatory parameters will be assessed at baseline, after one week (day +7) and at the end of treatment (day +14) Ruxolitinib will be associated to the standard of care for COVID-19 of each center. In case of an adverse effect or a need to discontinue the treatment, ruxolitinib should be suspended.

Primary Outcome Measure Information:

Title

Evaluate the efficacy of ruxolitinib in the treatment of COVID-19 severe acute respiratory syndrome

Description

Measuring the proportion of patients with clinical worsening (defined by a requirement of FIO2 >50% and/or mechanical respiratory assistance)

Time Frame

during 14 days after the commencement of treatment

Secondary Outcome Measure Information:

Title

Evaluate the median duration of hospitalization.

Time Frame

after 45 days of commencement of treatment.

Title

Evaluate the evolution of systemic inflammation parameters.

Description

Evaluation at the beginning (baseline), middle and end of the treatment with ruxolitinib of PCR, LDH, ESD, Ferritin and IL-6 (if available).

Time Frame

after 45 days of commencement of treatment.

Title

Evaluate COVID-19 mortality rate

Time Frame

after 45 days of treatment.

Title

Evaluate the proportion of the requirement of mechanical ventilation.

Time Frame

with a total follow-up of 45 days

Title

Evaluate ruxolitinib adverse reactions

Time Frame

with a total follow-up of 45 days.

Title

Evaluate the proportion of secondary infections during the treatment with ruxolitinib

Time Frame

after 45 days of commencement of treatment.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients ≥ 18 years. SARS-Cov2 infection confirmed by a validated method. Presence of COVID-19 severe acute respiratory syndrome with: Respiratory rate ≥ 20/min O2 saturation ≤93% with FiO2 of 0.21 Lung images by means of computerized tomography or thorax radiography compatible with respiratory involvement due to COVID-19. Signed informed consent. Exclusion Criteria: Pregnancy or breast-feeding. Platelets < 50,000/mm3. Neutrophils < 1,000/mm3. Hemoglobin < 6 g/dl Creatinine ≥2 mg/dl or creatinine clearance ≤30 ml/min. Total serum bilirubin > 2.0 x upper limit of normal and/or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 times the upper limit of normal. Known active infection due to HIV, HVC, HVB, Herpes Zoster or Micob Tuberculosis Treatment with Tocilizumab, Baricitinib or Interferon. History of hypersensitivity to ruxolitinib or to any medicine with similar chemical compounds Patients with mechanical respiratory assistance Patients under treatment with Ruxolitinib due to hematological disease Any condition that, according to the Investigator, may interfere with the complete participation of the patient in the study, including the administration of the medicinal product, the limitation of visits, the implication of a risk for the patient or that prevents the correct interpretation of the results. Treatment Suspension Criteria Voluntary decision of the patient Treating physician's decision to discontinue the treatment Drug toxicity grade 3 or higher (CTCAE 5.0). Study Design Experimental, open-label, prospective, single center, add-on (added to the standard treatment) study, compared with the historical control arm. Control arm: It will include patients with COVID-19 Respiratory Syndrome who meet the aforementioned selection criteria and have received the standard of care (SOC). Efforts will be made so that both arms share similar demographic characteristics as regards gender and age group. Ten centers will participate, which will share the same protocol and their results may be jointly analyzed. The expected n per center is 10-15 patients. For the safety assessment as part of the objective, the following parameters will be taken into account: Biochemical changes: (day 1, 8 and 14) Leukocytes, Formula, Hemoglobin, platelets, creatinine, glycemia, PT, Bilirubin, GOT/GPT. Grade 3/4 Toxicity, SAE (Serious Adverse Event) Incidence of discontinuation, suspension or dose-reduction of the study drug. Incidence of secondary infections. Efficacy Assessment: Efficacy will be graded according to the ordinal scale of 8 points. Time to Improvement Time of response consolidation Changes in NEWS table

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Marcelo Iastrebner, MD

Phone

+5491169816300

miastrebner@gmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Joaquin Castro, MD

Phone

+5491153880811

drjoaquincastro@gmail.com

12. IPD Sharing Statement

Citations:

PubMed Identifier

32150360

Citation

Cascella M, Rajnik M, Aleem A, Dulebohn SC, Di Napoli R. Features, Evaluation, and Treatment of Coronavirus (COVID-19). 2023 Aug 18. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK554776/

Results Reference

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PubMed Identifier

32251717

Citation

McGonagle D, Sharif K, O'Regan A, Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun Rev. 2020 Jun;19(6):102537. doi: 10.1016/j.autrev.2020.102537. Epub 2020 Apr 3.

Results Reference

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PubMed Identifier

28255960

Citation

Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects. Drugs. 2017 Apr;77(5):521-546. doi: 10.1007/s40265-017-0701-9. Erratum In: Drugs. 2017 May;77(8):939. Drugs. 2017 Jun 12;:

Results Reference

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PubMed Identifier

32194980

Citation

Zhou Y, Hou Y, Shen J, Huang Y, Martin W, Cheng F. Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2. Cell Discov. 2020 Mar 16;6:14. doi: 10.1038/s41421-020-0153-3. eCollection 2020.

Results Reference

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PubMed Identifier

29134683

Citation

Slostad J, Hoversten P, Haddox CL, Cisak K, Paludo J, Tefferi A. Ruxolitinib as first-line treatment in secondary hemophagocytic lymphohistiocytosis: A single patient experience. Am J Hematol. 2018 Feb;93(2):E47-E49. doi: 10.1002/ajh.24971. Epub 2017 Dec 4. No abstract available.

Results Reference

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PubMed Identifier

27211272

Citation

Harrison CN, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Gisslinger H, Knoops L, Cervantes F, Jones MM, Sun K, McQuitty M, Stalbovskaya V, Gopalakrishna P, Barbui T. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016 Aug;30(8):1701-7. doi: 10.1038/leu.2016.148. Epub 2016 May 23. Erratum In: Leukemia. 2017 Mar;31(3):775.

Results Reference

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PubMed Identifier

30806710

Citation

Gadina M, Le MT, Schwartz DM, Silvennoinen O, Nakayamada S, Yamaoka K, O'Shea JJ. Janus kinases to jakinibs: from basic insights to clinical practice. Rheumatology (Oxford). 2019 Feb 1;58(Suppl 1):i4-i16. doi: 10.1093/rheumatology/key432.

Results Reference

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Ruxolitinib in the Treatment of Covid-19

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