TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With COVID-19 Interstitial Pneumonia (TOFACoV-2)

TOFAcitinib Plus Hydroxycloroquine vs Hydroxycloroquine in Patients With Early Onset SARS-CoV2 (COVID-19) Interstitial Pneumonia:a Multicenter Randomized Controlled Open Label Trial

Multifocal interstitial pneumonia represents the most common cause of admission in intensive care units and death in SARS-CoV2 infections. In our Hospital, similarly to what reported in literature, up to 25% of admitted patients with pneumonitis requires mechanical ventilation or oro-tracheal intubation within 5-10 days. No established treatment is available for this condition. Preliminary evidence is accumulating about the efficacy of an aggressive treatment of the corona virus-induced inflammation and, in particular, investigators believe that blocking JAK1 is clinically rewarding in down-regulating IL-6 driven inflammation in patients with corona-virus infection. Thus, investigators designed a randomized controlled trial to test the hypothesis that adding Tofacitinib to the standard treatment in the early phase of COVID related pneumonitis could prevent the development of severe respiratory failure needing mechanical ventilation.

Study Overview

• Status: Unknown
• Conditions: COVID-19; Pneumonitis, Interstitial
• Intervention / Treatment: Drug: Tofacitinib; Drug: Hydroxychloroquine

• Study Type: Interventional
• Enrollment (Anticipated): 116
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Armando Gabrielli, MD; Phone Number: 0712206104; Email: a.gabrielli@staff.univpm.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• SARS-CoV2 Infection diagnosed by rt-PCR
• CT-scan confirmed interstitial pneumonia
• Hospital admission from less than 24h
• P/F ratio >150 mmHg
• 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)
• QTc > 470 ms or >500 ms in wide QRS patients
• Severe History of Chronic Ischemic Heart Disease, defined as history of Major Adverse Cardiovascular Event and/or recent (one year) revascularization.
• History of recurrent Deep Venous Thrombosis and Pulmonary Embolism or established thrombophilic conditions (e.g. history of anti-phospholipid antibodies, …)
• Active Bacterial or Fungal Infection
• Hematological cancer
• Metastatic or intractable cancer
• Pre-existent neurodegenerative disease
• Severe Hepatic Impairment,
• History of acute diverticular disease or intestinal perforation
• HBsAg positive and/or HBV-DNA positive patients
• Severe Renal Failure (Creatinine Clearance <30ml/h)
• Active Herpes zoster infection
• Patients with active or latent TB
• Severe anemia (Hb<9g/dl)
• Lymphocyte count below 750/mcl
• Neutrophil count below 1000/mcl
• Platelet count below 50000/mcl
• Pregnancy or Lactation
• History of intolerance to the experimental drugs or excipients
• Degenerative maculopathy or other relevant retinal disease
• Inability to give informed consent (severe transitory or permanent mental impairment, incapacitation)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: tofacitinib+HYQ; Tofacitinib 10mg cp twice a day + Hydroxychloroquine 200mg cp three times a day, both for 14 days	Drug: Tofacitinib; Jak-1/3 inhibitor; Other Names: Xeljanz; Drug: Hydroxychloroquine; Standard Therapy
ACTIVE_COMPARATOR: Hydroxychloroquine; Hydroxychloroquine 200mg cp three times a day for 14 days	Drug: Hydroxychloroquine; Standard Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of severe Respiratory Failure requiring mechanical ventilation	Rate of patients needing mechanical ventilation to maintain PaO2/FIO2>150	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of need of ICU admission	Rate of patients needing admission to the intensive care unit	28 days
Prevention of COVID-19 related Deaths	Rate of patients who die due to COVID-19 related conditions	28 days
Identification of predictors of outcome	Role of some clinical and laboratory factors in predicting outcome (Age, sex, smoking status, Body Mass Index (BMI), Comorbidities (Diabetes, number of comorbidities), Respiratory Failure at admission defined as PaO2/FiO2<300, Extension of Ct-scan involvement, basal level of serum IL-6, vW-Factor, Thrombomodulin, KL-6, sACE2 and SP-D )	14 days
Incidence of Treatment-Emergent Adverse Events	Rate of severe drug-related adverse events	28 days

Collaborators and Investigators

• Sponsor: Università Politecnica delle Marche
• Collaborators: Ospedale di Circolo e Fondazione Macchi, Varese; Azienda Ospedaliera Ospedali Riuniti Marche Nord; Ospedale Civile Santo Spirito, Pescara; Università Magna Grecia, Catanzaro; ASST Papa Giovanni XXIII, Bergamo; Azienda Ospedaliero Universitaria Policlinico Umberto I, Roma; ASST Cremona, Cremona; Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milano

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2020
• Primary Completion (ANTICIPATED): September 1, 2020
• Study Completion (ANTICIPATED): October 1, 2020

Study Registration Dates

• First Submitted: May 13, 2020
• First Submitted That Met QC Criteria: May 14, 2020
• First Posted (ACTUAL): May 15, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 15, 2020
• Last Update Submitted That Met QC Criteria: May 14, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia; Lung Diseases, Interstitial; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Tofacitinib; Hydroxychloroquine
• Other Study ID Numbers: 2020-002035-30

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No