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

Sponsor

Maria del Rosario Garcia de Vicuña Pinedo (Other)

Overall Status

Completed

CT.gov ID

NCT04357808

Collaborator

Instituto de Investigación Sanitaria Hospital Universitario de la Princesa (Other)

Enrollment

Location

Arms

7.7

Actual Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 Based in unpublished experiences in China, Italy and Spain, intravenous IL-6 receptor inhibitors are now being tested in several trials but no data on subcutaneous formulations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

Condition or Disease	Intervention/Treatment	Phase
Covid-19	Drug: Sarilumab Other: Standar of care	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomised, open-label, single-center, comparative trial of sarilumab plus standard of care vs. standard of care in a 2:1 ratio.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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 13, 2020

Actual Primary Completion Date :

Nov 30, 2020

Actual Study Completion Date :

Dec 4, 2020

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Mean change in clinical status assessment using the 7-point ordinal scale at day 7 after randomisation [7 days from enrolment]
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
Duration of hospitalisation (days) [30 days from enrolment]
Days from the date of enrolment to the date of discharge
Death [30 days from enrolment]
Number of deaths

Secondary Outcome Measures

Time to become afebrile (days) [30 days from enrolment]
Time to become afebrile for a minimum period of 48 hours, without antipyretics
Time to non-invasive mechanical ventilation (days) [30 days from enrolment]
Days from enrolment to non-invasive mechanical ventilation
Time to invasive mechanical ventilation (days) [30 days from enrolment]
Days from enrolment to invasive mechanical ventilation
Time to independence from supplementary oxygen therapy (days) [30 days from enrolment]
Days from enrolment to supplementary oxygen therapy withdrawal
Mean change in clinical status assessment using the 7-point ordinal scale at day 14 after randomisation [14 days from enrolment]
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

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.