Efficacy of Subcutaneous Sarilumab in Hospitalised Patients With Moderate-severe COVID-19 Infection (SARCOVID)

Study Overview
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Brief Summary
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The global health emergency created by the rapid spread of the SARS-CoV-2 coronavirus has pushed healthcare services to face unprecedent challenges to properly manage COVID-19 severe and critical manifestations affecting a wide population in a short period of time. Clinicians are committed to do their best with a great uncertainty in this evolving crisis. Off label use of plenty of drugs has arisen the need for clinical trials to demonstrate their true role in the therapy. Based in unpublished experiences in China, Italy and Spain, intravenous IL-6 receptor inhibitors are now being tested in several trials but no data on subcutaneous formulations are available yet. Sarilumab is a human monoclonal antibody that binds membrane-bound and soluble IL-6 receptors to inhibit IL-6 signalling, licensed in a subcutaneous route administration.

Detailed Description
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SARCOVID is an investigator-initiated monocentric randomised proof of concept study that aims to evaluate the efficacy and safety of a single dose of sarilumab, in subcutaneous administration, in hospitalised patients with moderate to early severe COVID-19 infection, compared to the current standard of care.

Official Title
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Randomized Open Pilot Study to Evaluate the Efficacy of Subcutaneous Sarilumab in Patients With Moderate-severe COVID-19 Infection

Conditions
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Covid-19

Intervention / Treatment
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* Drug: Sarilumab
* Other: Standar of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age> 18 years Laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other validated commercial or public health assay Documented interstitial pneumonia requiring admission and at least two of the following: Fever ≥ 37.8ºC (tympanic) IL-6 in serum ≥ 25 ng / mL (in the absence of a previous dose of prednisone or equivalent> 1 mg / kg) or PCR> 5mg / dL Lymphocytes <600 mm3 Ferritin> 300 mcg / L that doubles in 24 hours Ferritin> 600 mcg / L in the first determination and LDH> 250 U / L D-dimer (> 1 mg / L) Informed verbal or administration consent under urgent conditions, documented in the electronic medical record. Exclusion Criteria: Patients who require mechanical ventilation at the time of inclusion. AST / ALT values > 5 folds upper normal limit. Neutrophil count below 500 cells / mm3 Platelet count below 50,000 cells / mm3 Documented sepsis or high suspicion by pathogens other than COVID-19. Presence of comorbidities that according to clinical judgment could lead to an unfavorable result. Complicated diverticulitis or intestinal perforation. Current skin infection (eg, uncontrolled dermopiodermitis). Immunosuppressive anti-rejection therapy. Pregnancy or lactation. Previous treatment with tocilizumab or sarilumab. Patients participating in some other clinical trial for SARS-CoV-2 infection. Patients with known hypersensitivity or contraindication to sarilumab or excipients.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomised, open-label, single-center, comparative trial of sarilumab plus standard of care vs. standard of care in a 2:1 ratio.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sarilumab plus standard of care<br>Sarilumab 200 mg, 2 sc injections in pre-filled syringe or pen, single dose. Treatment with drugs or procedures in routine clinical practice that the clinician responsible for the patient deems necessary is allowed | Drug: Sarilumab<br>* Single dose treatment with sarilumab 2 x 200 mg subcutaneously<br>* Other names: SAR153191;|
| Active Comparator: Standard of care<br>Treatment with drugs or procedures in routine clinical practice | Other: Standar of care<br>* Usual clinical care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in clinical status assessment using the 7-point ordinal scale at day 7 after randomisation | Score ranges 1-7 Death; Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); Hospitalized, requiring non-invasive ventilation or high flow oxygen devices; Hospitalized, requiring supplemental oxygen; Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care Not hospitalized | 7 days from enrolment | 
| Duration of hospitalisation (days) | Days from the date of enrolment to the date of discharge | 30 days from enrolment | 
| Death | Number of deaths | 30 days from enrolment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to become afebrile (days) | Time to become afebrile for a minimum period of 48 hours, without antipyretics | 30 days from enrolment | 
| Time to non-invasive mechanical ventilation (days) | Days from enrolment to non-invasive mechanical ventilation | 30 days from enrolment | 
| Time to invasive mechanical ventilation (days) | Days from enrolment to invasive mechanical ventilation | 30 days from enrolment | 
| Time to independence from supplementary oxygen therapy (days) | Days from enrolment to supplementary oxygen therapy withdrawal | 30 days from enrolment | 
| Mean change in clinical status assessment using the 7-point ordinal scale at day 14 after randomisation | Scale ranges 1-7: Death Hospitalized, with mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Hospitalized, with non-invasive mechanical ventilation, a mask with a reservoir or oxygen with high flow nasal goggles. Hospitalized with oxygen supplement Hospitalized, without oxygen supplement, but in need of continued medical care (related or not with COVID) Hospitalized, without oxygen supplement and without the need for continued medical care Not hospitalized | 14 days from enrolment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID, SARS-CoV-2, coronavirus infections, sarilumab, IL-6 receptor inhibitors