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

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

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 Based in unpublished experiences in China, Italy and Spain, intravenous IL-6 receptor inhibitors are now being tested in several trials but no data on subcutaneous formulations are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.

Study Overview

• Status: Completed
• Conditions: Covid-19
• Intervention / Treatment: Drug: Sarilumab; Other: Standar of care

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. Fever ≥ 37.8ºC (tympanic)
  2. 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
  3. Lymphocytes <600 mm3
  4. Ferritin> 300 mcg / L that doubles in 24 hours
  5. Ferritin> 600 mcg / L in the first determination and LDH> 250 U / L
  6. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sarilumab plus standard of care; 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; Single dose treatment with sarilumab 2 x 200 mg subcutaneously; Other Names: Kevzara; SAR153191
Active Comparator: Standard of care; Treatment with drugs or procedures in routine clinical practice	Other: Standar of care; Usual clinical care

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of serious and non-serious adverse events.	Number of adverse events and number of patients with adverse events	30 days after enrolment
Discontinuation due to adverse reactions	Number of adverse reactions that requires discontinuation of any drug in the study	30 days after enrolment

Collaborators and Investigators

• Sponsor: Maria del Rosario Garcia de Vicuña Pinedo
• Collaborators: Instituto de Investigación Sanitaria Hospital Universitario de la Princesa
• Investigators: Principal Investigator: Rosario Garcia de Vicuña, MD PhD, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Publications and helpful links

General Publications

• García-Vicuña R, Rodriguez-García SC, Abad-Santos F, Bautista Hernández A, García-Fraile L, Barrios Blandino A, Gutiérrez Liarte A, Alonso-Pérez T, Cardeñoso L, Alfranca A, Mejía-Abril G, Sanz Sanz J, González-Alvaro I. Subcutaneous IL-6 Inhibitor Sarilumab vs. Standard Care in Hospitalized Patients With Moderate-To-Severe COVID-19: An Open Label Randomized Clinical Trial. Front Med (Lausanne). 2022 Feb 23;9:819621. doi: 10.3389/fmed.2022.819621. eCollection 2022.
• Garcia-Vicuna R, Abad-Santos F, Gonzalez-Alvaro I, Ramos-Lima F, Sanz JS. Subcutaneous Sarilumab in hospitalised patients with moderate-severe COVID-19 infection compared to the standard of care (SARCOVID): a structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Sep 9;21(1):772. doi: 10.1186/s13063-020-04588-5.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2020
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): December 4, 2020

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 20, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): February 11, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID; coronavirus infections; sarilumab; IL-6 receptor inhibitors
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections
• Other Study ID Numbers: SARCOVID; 2020-001634-36 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No