TOFAcitinib in SARS-CoV2 Pneumonia

SARS-COv2 Related Interstitial Pneumonia Clinical Trial

Official title:

TOFAcitinib in Patients With Early Onset SARS-CoV2 Interstitial Pneumonia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04332042
• Other study ID #: TOFACoV
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 10, 2020
• Est. completion date: July 10, 2020

Study information

• Verified date: April 2020
• Source: Università Politecnica delle Marche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: July 10, 2020
• Est. primary completion date: June 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Lung Diseases, Interstitial
• Pneumonia
• SARS-COv2 Related Interstitial Pneumonia

Intervention

Drug:
• Tofacitinib
Tofacitinib 10mg twice a day will be administered within 24h from hospital admission for 14 days

Locations

Country	Name	City	State
Italy	Ospedali Riuniti di Ancona	Ancona	Marche

Sponsors (1)

Lead Sponsor	Collaborator
Università Politecnica delle Marche

Country where clinical trial is conducted

Italy, 

References & Publications (5)

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). pii: E186. doi: 10.3390/pathogens9030186. Review. — View 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. — View 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. — View Citation

Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary Pathology of Early-Phase 2019 Novel Coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer. J Thorac Oncol. 2020 Feb 28. pii: S1556-0864(20)30132-5. doi: 10.1016/j.jtho.2020.02.010. [Epub ahead of print] — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	need of mechanical ventilation	Rate of patients needing mechanical ventilation to maintain PaO2/FIO2>150 or, if PaO2 data not available, to maintain SO2>94% with FiO2 0,5.	day 14
Secondary	need of admission in intensive care unit	Rate of patients needing admission to the intensive care unit for oro-tracheal intubation and/or evidence of Multiple Organ Disfunction	day 14
Secondary	death	rate of patients dead	day 28
Secondary	rate of adverse events	rate and type of adverse events	day 28