TOFAcitinib in SARS-CoV2 Pneumonia

• ClinicalTrials.gov Identifier: NCT04332042
• Recruitment Status: Unknown
• First Posted: April 2, 2020
• Last Update Posted: April 2, 2020
• Sponsor: Università Politecnica delle Marche
• Information provided by (Responsible Party): Armando Gabrielli, Università Politecnica delle Marche

Study Description

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.

Condition or disease	Intervention/treatment	Phase
SARS-COv2 Related Interstitial Pneumonia	Drug: Tofacitinib	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: prospective cohort study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: TOFAcitinib in Patients With Early Onset SARS-CoV2 Interstitial Pneumonia
• Estimated Study Start Date: April 10, 2020
• Estimated Primary Completion Date: June 20, 2020
• Estimated Study Completion Date: July 10, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: tofacitinib; Tofacitinib cp 5mg: 2pills twice a day for 14 days	Drug: Tofacitinib; Tofacitinib 10mg twice a day will be administered within 24h from hospital admission for 14 days

Outcome Measures

Primary Outcome Measures :

1. need of mechanical ventilation [ Time Frame: day 14 ]
   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.

Secondary Outcome Measures :

1. need of admission in intensive care unit [ Time Frame: day 14 ]
   Rate of patients needing admission to the intensive care unit for oro-tracheal intubation and/or evidence of Multiple Organ Disfunction
2. death [ Time Frame: day 28 ]
   rate of patients dead
3. rate of adverse events [ Time Frame: day 28 ]
   rate and type of adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

Italy

Ospedali Riuniti di Ancona

Ancona, Marche, Italy, 60126

Contact: Armando Gabrielli, Prof +390712206104 a.gabrielli@staff.univpm.it

Principal Investigator: Armando Gabrielli, Prof

Sub-Investigator: Giovanni Pomponio, Dr

Sponsors and Collaborators

Università Politecnica delle Marche

More Information

Publications:

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 May;15(5):700-704. doi: 10.1016/j.jtho.2020.02.010. Epub 2020 Feb 28.

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.

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.

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.

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.

• Responsible Party: Armando Gabrielli, Full Professor Internal Medicine, Università Politecnica delle Marche
• ClinicalTrials.gov Identifier: NCT04332042
• Other Study ID Numbers: TOFACoV
• First Posted: April 2, 2020
• Last Update Posted: April 2, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Tofacitinib; Pneumonia; COVID-19; Lung Diseases, Interstitial; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action