Clinical trial NCT04332042: TOFAcitinib in SARS-CoV2 Pneumonia
Official title: TOFAcitinib in Patients With Early Onset SARS-CoV2 Interstitial Pneumonia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: SARS-COv2 Related Interstitial Pneumonia
Lead sponsor: Università Politecnica delle Marche
Sponsor class: OTHER
First posted: 2020-04-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: prospective cohort study
Primary purpose: TREATMENT

Brief summary: Immune-mediated lung injury plays a pivotal role in severe interstitial pnemumonia related to SARS-CoV2 infection. Tofacitinib, a JAK1/3-Inhibitor, could mitigate alveolar inflammation by blocking IL-6 signal. The aim of this prospective single cohort open study is to test the hypotesis that early administration of tofacitinib in patients with symptomatic pneumonia could reduce pulmonary flogosis, preventing function deterioration and the need of mechanical ventilation and/or admission in intensive care units.

Detailed description: Interstitial Pneumonia is the main complication of SARS-CoV2 infection. Immune system hyperactivation, leading to alveolar inflammation, is the main mechanism in determining lung damage. Evidence are accumulating about the pivotal role played by IL-6 in this disease. Preliminary evidence, indeed, point out the efficacy of an IL-6 receptor inhibitor in improving clinical conditions in a proportion of rapidly deteriorating patients. Our hypotesis is that a precocious inhibition of IL-6 signal, by the administration of tofacitinib (JAK 1/3 Inhibitor), could hinder the progression to more severe grades of lung inflammation leading to pulmonary function deterioration. In a prospective single cohort open study, 50 patients admitted in Hospital due to SARS-CoV 2 symptomatic interstitial pneumonia, but not requiring mechanical ventilation, will be enrolled. Tofacitinb will be administered every day for 14 days, starting within 24 h from the admission. The primary outcome is to evaluate the effect of this drug on the rate of patients who will need mechanical ventilation. Safety in this population will also be actively monitored.

Eligibility criteria: Inclusion Criteria:

* SARS-CoV2 Infection diagnosed by rt-PCR
* Rx or CT-scan confirmed interstitial pneumonia
* Hospital admission from less than 24h
* Written Informed Consent

Exclusion Criteria:

* Age \<18 ys or \>65
* Patients in mechanical ventilation at time of admission
* Severe Hearth failure (NYHA 3 or 4)
* Severe History of Chronic Ischemic Hearth Disease, defined as history of Major Adverse Cardiovascular Event and/or recent (one year) revascularization.
* History of recurrent Deep Venous Thrombosis and Pulmonary Embolism
* Active Bacterial or Fungal Infection
* Hematological cancer
* Metastatic or intractable cancer
* Pre-existent neurodegenerative disease
* Severe Hepatic Impairment
* Severe Renal Failure (Creatinine Clearance \<30ml/h)
* Active Herpes zoster infection
* Severe anemia (Hb\<9g/dl)
* Lymphocyte count below 750/mcl
* Neutrophil count below 1000/mcl
* Platelet count below 50000/mcl
* Pregnancy or Lactation
* Inability to give informed consent (severe transitory or permanent mental impairment, incapacitation)

Primary outcomes:
measure: need of mechanical ventilation
timeFrame: day 14
Secondary outcomes:
measure: need of admission in intensive care unit
timeFrame: day 14
measure: death
timeFrame: day 28
measure: rate of adverse events
timeFrame: day 28
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: Ospedali Riuniti di Ancona
state: Marche
Study officials:
References:
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citation: Ashour HM, Elkhatib WF, Rahman MM, Elshabrawy HA. Insights into the Recent 2019 Novel Coronavirus (SARS-CoV-2) in Light of Past Human Coronavirus Outbreaks. Pathogens. 2020 Mar 4;9(3):186. doi: 10.3390/pathogens9030186.
citation: Zumla A, Hui DS, Azhar EI, Memish ZA, Maeurer M. Reducing mortality from 2019-nCoV: host-directed therapies should be an option. Lancet. 2020 Feb 22;395(10224):e35-e36. doi: 10.1016/S0140-6736(20)30305-6. Epub 2020 Feb 5. No abstract available.
citation: Rose-John S, Scheller J, Schaper F. "Family reunion"--A structured view on the composition of the receptor complexes of interleukin-6-type and interleukin-12-type cytokines. Cytokine Growth Factor Rev. 2015 Oct;26(5):471-4. doi: 10.1016/j.cytogfr.2015.07.011. Epub 2015 Jul 6. No abstract available.
citation: McInnes IB, Byers NL, Higgs RE, Lee J, Macias WL, Na S, Ortmann RA, Rocha G, Rooney TP, Wehrman T, Zhang X, Zuckerman SH, Taylor PC. Comparison of baricitinib, upadacitinib, and tofacitinib mediated regulation of cytokine signaling in human leukocyte subpopulations. Arthritis Res Ther. 2019 Aug 2;21(1):183. doi: 10.1186/s13075-019-1964-1.