SARS-COv2 Related Interstitial PneumoniaPhase 2NCT04332042
TOFAcitinib in SARS-CoV2 Pneumonia
A Phase 2 study testing Tofacitinib in people with SARS-COv2 Related Interstitial Pneumonia, run by Università Politecnica delle Marche at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- SARS-COv2 Related Interstitial Pneumonia
- What is being tested?
- Tofacitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- 10 Apr 2020to 10 Jul 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- SARS-CoV2 Infection diagnosed by rt-PCR
- Rx or CT-scan confirmed interstitial pneumonia
- Hospital admission from less than 24h
- Written Informed Consent
Who cannot join
- 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
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- 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)
Trial locations and contacts
1 site in 1 country.
Italy1 site
Ospedali Riuniti di Ancona
Ancona, The Marches, 60126
Armando Gabrielli, Prof, +390712206104, a.gabrielli@staff.univpm.it
Armando Gabrielli, Prof
About this study
Official title: TOFAcitinib in Patients With Early Onset SARS-CoV2 Interstitial Pneumonia
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.
Read the 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.
- Conditions
- SARS-COv2 Related Interstitial Pneumonia
- Being tested
- Tofacitinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TofacitinibDrug
Tofacitinib 10mg twice a day will be administered within 24h from hospital admission for 14 days
| Study group | Role | What they receive |
|---|---|---|
| tofacitinib | Experimental | Tofacitinib cp 5mg: 2pills twice a day for 14 days Receives: Drug: Tofacitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: day 14
Secondary outcomes (3)
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
Measured: day 14
death
rate of patients dead
Measured: day 28
rate of adverse events
rate and type of adverse events
Measured: day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2020
- Study start10 Apr 2020 (estimated)
- Primary completion20 Jun 2020 (estimated)
- Study completion10 Jul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for SARS-COv2 Related Interstitial PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- prospective cohort study
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Università Politecnica delle Marche
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Armando Gabrielli, Università Politecnica delle Marche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04332042
- Sponsor's protocol ID
- TOFACoV
- Status last verified
- Apr 2020
- First submitted
- 28 Mar 2020
- Last updated
- 2 Apr 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 32114094Ashour 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.
PubMed 32143502Zumla 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.
PubMed 32035018Rose-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.
PubMed 26235233McInnes 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.
PubMed 31375130
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TOFAcitinib in Patients With Early Onset SARS-CoV2 Interstitial Pneumonia
- ClinicalTrials.gov ID
- NCT04332042
- Acronym / sponsor ID
- TOFACoV
- Conditions
- SARS-COv2 Related Interstitial Pneumonia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Università Politecnica delle MarcheUniversity, hospital or other
- Study start
- 10 Apr 2020 (estimated)
- Primary completion
- 20 Jun 2020 (estimated)
- Study completion
- 10 Jul 2020 (estimated)
- First posted
- 2 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- prospective cohort study
| Arm | Type | Receives |
|---|---|---|
| tofacitinib | Experimental | Drug: TofacitinibTofacitinib cp 5mg: 2pills twice a day for 14 days |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- SARS-CoV2 Infection diagnosed by rt-PCR
- Rx or CT-scan confirmed interstitial pneumonia
- Hospital admission from less than 24h
- Written Informed Consent
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TofacitinibTofacitinib 10mg twice a day will be administered within 24h from hospital admission for 14 days | Drug | tofacitinib |
Primary outcome
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.
3 secondary outcomes
need of admission in intensive care unit
Time frame: day 14
death
Time frame: day 28
rate of adverse events
Time frame: day 28
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2020.
- Background: PubMed 32114094Tian 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.
- Background: PubMed 32143502Ashour 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.
- Background: PubMed 32035018Zumla 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.
- Background: PubMed 26235233Rose-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.
- Background: PubMed 31375130McInnes 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.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tofacitinib in people with SARS-COv2 Related Interstitial Pneumonia, run by Università Politecnica delle Marche at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
need of mechanical ventilation (time frame: day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04332042, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2020.