A Phase 2 Trial of Infliximab in Coronavirus Disease 2019 (COVID-19).

Study Overview
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Brief Summary
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The investigators hypothesize that early institution of TNFα inhibitor therapy in patients with severe COVID-19 infections will prevent further clinical deterioration and reduce the need for advanced cardiorespiratory support and early mortality. To address this hypothesis, a prospective, single center, phase 2 trial is proposed to assess the efficacy of infliximab or infliximab-abda in hospitalized adult patients with severe or critical COVID-19. Observations from this study will inform the conduct of prospective randomized controlled studies to follow.

Detailed Description
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The investigators hypothesize that early institution of TNFα inhibitor therapy in patients with severe COVID-19 infections will prevent further clinical deterioration and reduce the need for advanced cardiorespiratory support and early mortality. To address this hypothesis, a prospective, single center, phase 2 trial is proposed to assess the efficacy of infliximab or infliximab-abda in hospitalized adult patients with severe or critical COVID-19. Observations from this study will inform the conduct of prospective randomized controlled studies to follow. Infliximab and Infliximab-abda are TNFα inhibitors currently FDA-approved for the treatment of autoimmune disorders, including Crohn's disease and rheumatoid arthritis. The risks and adverse reactions are described in the approved prescribing information for infliximab (or infliximab-abda). Infliximab will be used when available. Should infliximab be unavailable in the pharmacy, infliximab-abda, a biosimilar, will be used. Treatment with infliximab or infliximab-abda 5mg/kg IV should ideally be administered within 6 hours of enrollment, and no more than 24 hours following enrollment. Pre-medication with Tylenol 650 mg once 30 minutes prior to infusion would be recommended. Other pre-medications may be given at the discretion of the treating physician. These include diphenhydramine 50mg by mouth, as well as prednisone 20mg by mouth, both given 30 minutes prior to infusion. Pulse and blood pressure should be monitored every 30 minutes during the infusion, and patients should be monitored for at least 30 minutes following the infusion. Retreatment with infliximab is permitted at treating physician discretion 7-21 days following primary therapy and based on initial response; the usual treatment schedule is every 2 weeks, this interval is not strictly enforced given the uncertainty of outcomes with primary therapy.

Official Title
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A Phase 2 Trial of Infliximab in Coronavirus Disease 2019 (COVID-19).

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Able to provide informed consent Hospitalized adult patients with pneumonia evidenced by chest X-ray or CT scan Laboratory (RT-PCR) confirmed infection with 2019-nCoV or strongly suspected to be infected with SARS-COV2 with confirmation studies pending And at least one of the following: Respiratory frequency ≥30/min Blood oxygen saturation ≤93% on RA Partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <300 Worsening of lung involvement, defined as an increase in number and/or extension of pulmonary areas of consolidation, need for increased FiO2 to maintain stable O2 saturation, or worsening O2 saturation of >3% with stable FiO2 Exclusion Criteria: Treatment with any TNFα inhibitor in the past 30 days Known hypersensitivity to any TNFα inhibitor, murine proteins, or any component of the formulation Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 1000 mm3, hemoglobin <8.0g/L, platelets <50,000 per mm3, or AST or ALT greater than 5 x ULN Known active or latent Hepatitis B Known or suspected active tuberculosis (TB) or a history of incompletely treated or latent TB. Pregnancy Intubated for >48hours Patients with uncontrolled systemic bacterial or fungal infections (Patients with a history of positive bacterial or fungal cultures but on enrollment are on appropriate therapy with negative repeat cultures may be enrolled) Serious co-morbidity, including: Myocardial infarction (within last month) Moderate or severe heart failure (New York Heart Association (NYHA) class III or IV) Acute stroke (within last month) Uncontrolled malignancy Stage 4 severe chronic kidney disease or requiring dialysis (i.e. estimated glomerular filtration rate (eGFR) < 30 ml /min/1.73 m^2) at baseline

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infliximab<br>All patients enrolled into this trial will be assigned to the Infliximab arm. Patients will be treated with infliximab on Day 1, and may be re-treated per protocol and at the discretion of the investigator. | Drug: Infliximab<br>* Either infliximab or infliximab-abda will be used at the discretion of the investigator<br>* Other names: infliximab-abda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Improvement in Oxygenation | Time to improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2) | 28 Days | 
| Number of p[Atients With Improvement in Oxygenation | Number of participants who showed improvement in oxygenation (increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2) | 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28-Day Survival Status | Number of patients who were confirmed to be alive 28 days from enrollment onto the study. | 28 Days | 
| Duration of Supplemental Oxygen Administration by Nasal Cannula | Duration of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device | 28 Days | 
| Duration of Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula | Duration of non-invasive ventilation or by non-rebreather mask or high-flow nasal cannula | 28 Days | 
| Number of Patients Requiring Mechanical Ventilation | Number of patients enrolled who required mechanical ventilation | 28 Days | 
| Number of Patients Requiring Vasopressor Support | Number of participants who required vasopressor support | 28 Days | 
| Number of Patients Requiring Extracorporeal Membrane Oxygenation | Number of patients requiring extracorporeal membrane oxygenation | 28 Days | 
| Number of Patients With Fever | Number of patients who exhibited fever during the study period | 28 Days | 
| Correlation of Dynamic Changes in IP-10 to Cytokine Profile | Correlation of dynamic changes in IP-10 to cytokine profile between day 3 and baseline | 3 Days | 
| Duration of Hospitalization | Duration of hospitalization | 28 Days | 
| Number of Patients Who Developed Secondary Infections | Number of patients who developed secondary infections | 28 Days | 
| Number of Patients Requiring Supplemental Oxygen Administration by Nasal Cannula | Incidence of supplemental oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device | 28 Days | 
| Duration of Mechanical Ventilation | duration of use of mechanical ventilation (for patients requiring mechanical ventilation) | 28 Days | 
| Number of Patients Requiring Non-invasive Ventilation or by Non-rebreather Mask or High-flow Nasal Cannula | Number of participants who required non-invasive ventilation or by non-rebreather mask or high-flow nasal cannula | 28 Days | 
| Assessment of Cytokine and Inflammatory Profile at Baseline | Assessment of cytokine and inflammatory profile at baseline (TNFα, IL-1b, IL-2, IL-6, ferritin) after therapy | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19