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

• ClinicalTrials.gov Identifier: NCT04357808
• Recruitment Status: Completed
• First Posted: April 22, 2020
• Last Update Posted: February 11, 2021
• Sponsor: Maria del Rosario Garcia de Vicuña Pinedo
• Collaborator: Instituto de Investigación Sanitaria Hospital Universitario de la Princesa
• Information provided by (Responsible Party): Maria del Rosario Garcia de Vicuña Pinedo, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Tracking Information

• First Submitted Date: April 14, 2020
• First Posted Date: April 22, 2020
• Last Update Posted Date: February 11, 2021
• Actual Study Start Date: April 13, 2020
• Actual Primary Completion Date: November 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 20, 2020)

• Mean change in clinical status assessment using the 7-point ordinal scale at day 7 after randomisation [ Time Frame: 7 days from enrolment ]
  Score ranges 1-7

  1. Death;
  2. Hospitalized, requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO);
  3. Hospitalized, requiring non-invasive ventilation or high flow oxygen devices;
  4. Hospitalized, requiring supplemental oxygen;
  5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
  6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
  7. Not hospitalized
• Duration of hospitalisation (days) [ Time Frame: 30 days from enrolment ]
  Days from the date of enrolment to the date of discharge
• Death [ Time Frame: 30 days from enrolment ]
  Number of deaths

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 20, 2020)

• Time to become afebrile (days) [ Time Frame: 30 days from enrolment ]
  Time to become afebrile for a minimum period of 48 hours, without antipyretics
• Time to non-invasive mechanical ventilation (days) [ Time Frame: 30 days from enrolment ]
  Days from enrolment to non-invasive mechanical ventilation
• Time to invasive mechanical ventilation (days) [ Time Frame: 30 days from enrolment ]
  Days from enrolment to invasive mechanical ventilation
• Time to independence from supplementary oxygen therapy (days) [ Time Frame: 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 [ Time Frame: 14 days from enrolment ]
  Scale ranges 1-7:

  1. Death
  2. Hospitalized, with mechanical ventilation or extracorporeal membrane oxygenation (ECMO).
  3. Hospitalized, with non-invasive mechanical ventilation, a mask with a reservoir or oxygen with high flow nasal goggles.
  4. Hospitalized with oxygen supplement
  5. Hospitalized, without oxygen supplement, but in need of continued medical care (related or not with COVID)
  6. Hospitalized, without oxygen supplement and without the need for continued medical care
  7. Not hospitalized

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: April 20, 2020)

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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Efficacy of Subcutaneous Sarilumab in Hospitalised Patients With Moderate-severe COVID-19 Infection (SARCOVID)
• Official Title: Randomized Open Pilot Study to Evaluate the Efficacy of Subcutaneous Sarilumab in Patients With Moderate-severe COVID-19 Infection
• 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.
• 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
• Study Phase: Phase 2

Study Design

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.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Covid-19

Intervention

• Drug: Sarilumab
  Single dose treatment with sarilumab 2 x 200 mg subcutaneously
  Other Names:

  • Kevzara
  • SAR153191
• Other: Standar of care
  Usual clinical care

Study Arms

• 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
  Intervention: Drug: Sarilumab
• Active Comparator: Standard of care
  Treatment with drugs or procedures in routine clinical practice
  Intervention: Other: Standar of care

• Publications *: Garcia-Vicuña R, Abad-Santos F, González-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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 20, 2020): 30
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 4, 2020
• Actual Primary Completion Date: November 30, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Spain

Administrative Information

• NCT Number: NCT04357808
• Other Study ID Numbers: SARCOVID; 2020-001634-36 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Responsible Party: Maria del Rosario Garcia de Vicuña Pinedo, Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• Study 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

• PRS Account: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa
• Verification Date: February 2021