Clinical trial NCT04414098: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19
Keywords: Ruxolitinib
Covid-19
SARS
Lead sponsor: Clinica Zabala
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2020-06-04
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Experimental, open-label, prospective, single center, add-on (added to the standard treatment) study, compared with an historical control arm.
Primary purpose: TREATMENT

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

1. Evaluate the median duration of hospitalization. Median duration after 45 days of commencement of treatment.
2. 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.
3. Evaluate COVID-19 mortality rate after 45 days of treatment.
4. Evaluate the proportion of the requirement of mechanical ventilation.
5. Evaluate ruxolitinib adverse reactions with a total follow-up of 45 days.
6. Evaluate the proportion of secondary infections during the treatment with ruxolitinib.

Eligibility criteria: Inclusion Criteria:

1. Patients ≥ 18 years.
2. SARS-Cov2 infection confirmed by a validated method.
3. 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.
4. Signed informed consent.

Exclusion Criteria:

1. Pregnancy or breast-feeding.
2. Platelets \< 50,000/mm3.
3. Neutrophils \< 1,000/mm3.
4. Hemoglobin \< 6 g/dl
5. Creatinine ≥2 mg/dl or creatinine clearance ≤30 ml/min.
6. 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.
7. Known active infection due to HIV, HVC, HVB, Herpes Zoster or Micob Tuberculosis
8. Treatment with Tocilizumab, Baricitinib or Interferon.
9. History of hypersensitivity to ruxolitinib or to any medicine with similar chemical compounds
10. Patients with mechanical respiratory assistance
11. Patients under treatment with Ruxolitinib due to hematological disease
12. 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

1. Voluntary decision of the patient
2. Treating physician's decision to discontinue the treatment
3. 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:

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

Efficacy Assessment:

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

Primary outcomes:
measure: Evaluate the efficacy of ruxolitinib in the treatment of COVID-19 severe acute respiratory syndrome
timeFrame: during 14 days after the commencement of treatment
Secondary outcomes:
measure: Evaluate the median duration of hospitalization.
timeFrame: after 45 days of commencement of treatment.
measure: Evaluate the evolution of systemic inflammation parameters.
timeFrame: after 45 days of commencement of treatment.
measure: Evaluate COVID-19 mortality rate
timeFrame: after 45 days of treatment.
measure: Evaluate the proportion of the requirement of mechanical ventilation.
timeFrame: with a total follow-up of 45 days
measure: Evaluate ruxolitinib adverse reactions
timeFrame: with a total follow-up of 45 days.
measure: Evaluate the proportion of secondary infections during the treatment with ruxolitinib
timeFrame: after 45 days of commencement of treatment.
Other outcomes:
Locations:
Study officials:
References:
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; 2025 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK554776/
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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.
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.
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.