Study on the Use of Sarilumab in Patients With COVID-19 Infection

Pilot Study on the Use of Sarilumab in Patients With COVID-19 Infection

Sarilumab is an anti-interleukin-6 human monoclonal antibody, such as tocilizumab, which is administered subcutaneously every two weeks for the treatment of moderate to severe active rheumatoid arthritis in adult patients. Despite the effectiveness reported for tocilizumab in the recently published experiences, the need to rapidly find alternative therapies to manage the complications of Covid-19 infection remains extremely high. The lack of clinical experience on the usage of sarilumab in such patients prevents the possibility of adopting early access programs for using commercially available sarilumab (prefilled syringe) packs in patients with severe Covid-19 pneumonia. The present study is aimed to generate a rapid, still robustly documented, evidence on the potential clinical efficacy and tolerability of a further IL-6R antagonist in Covid-19 pneumonia.

Study Overview

• Status: Recruiting
• Conditions: COVID19
• Intervention / Treatment: Drug: Sarilumab Prefilled Syringe

Detailed Description

In February 2020, the emergence of the COVID-19 epidemic in Italy and, especially, in Lombardy, with a potential fatal outcome in a significant proportion of cases, determined the need for adopting new therapeutic approached based on the few data available in literature. Although there are no clinical data available in COVID-19 patients concomitantly treated with Sarilumab subcutaneously (SC) nor intravenously (IV), there is scientific rationale that supports the exploration of sarilumab to treat pulmonary complications related to Covid-195-6. By inhibiting interleukin-6 (IL-6)signaling, sarilumab may potentially interrupt cytokine-mediated pulmonary injury precipitated by infection with SARS-CoV-2 and thereby ameliorate severity and/or reduce mortality among patients presenting with Covid-19 pneumonia when administered in conjunction with antiviral therapy. given the apparent dose/dose pharmacokinetic/ pharmacodynamic (PK/PD) equivalence of 400 mg of tocilizumab to 400 mg of sarilumab, we propose a dose escalation protocol by which the first 5 included patients will be treated with a dosage of 200 mg of sarilumab IV as 1st dose, followed by clinical reassessment after 12 hours and in case of no major adverse events and lack of improvement in respiratory function and / or persistence of fever and persistently high inflammatory markers re-administration of 200 mg intravenous (IV) of sarilumab. If no patients showed unfavorable safety signals, and no clear improvement is detected in >50% of the initially treated five patients after 96 hours since last administration, the dosage will be increase to sarilumab 400 mg IV as first and second dose in the remaining patients.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Agostino Riva, MD; Phone Number: 02-39042676; Email: agostino.riva@unimi.it
• Study Contact Backup: Name: Massimo Galli, Professor; Email: massimo.galli@unimi.it

Study Locations

• Italy
  • MI
    • Milano, MI, Italy, 20157
      • Recruiting
      • Divisione Clinicizzata di Malattie Infettive, ASST FBF-Sacco
      • Contact: Agostino Riva, M.D.; Phone Number: 00390239042676; Email: agostino.riva@unimi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years and < 85 years.
• Documented (chest X-Ray or TC scan), severe (BCRSS ≥3 and <4) interstitial pneumonia with respiratory failure (requiring supplemental oxygen) with positive Covid-19 swab testing.
• Worsening of respiratory exchanges such as to require ventilation with Venturi mask >31% (6L/minute).
• Increased levels of D-dimer (> 1500 ng/mL) or D-dimer progressively increasing (over 3 consecutive measurements) and reaching ≥ 1000 ng/mL.
• Signed informed consent.

Exclusion Criteria:

• Age < 18 years or ≥ 85 years.
• AST / ALT > 5x Upper normal limit.
• Neutrophil count lower than 500 cells / mL.
• Platelet count lower than 50,000 cells / mL.
• Documented sepsis due to infections other than Covid-19.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Covid-19; Patients with documented (chest X-Ray or Computed Tomography scan) Covid-19 (Polymerase Chain Reaction+ swab test) interstitial pneumonia and BCRSS ≥3 and <4 will be requested consent to the study.	Drug: Sarilumab Prefilled Syringe; Sarilumab administration must be associated with an antiviral treatment as defined by the treatment protocol suggested by the SIMET Experts group 4 and AIFA recommendations: chloroquine 500 mg 1 tablet twice daily or hydroxychloroquine 400 mg 1 tablet twice daily in the first day and then 200 mg 1 tablet twice daily.; Other Names: Sarilumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients who show an improvement of the respiratory function	Clinical efficacy of sarilumab in adult patients hospitalized due to severe Covid-19 pneumonia based on the proportion of patients who show an improvement of the respiratory function, described as ≥30% decrease in oxygen requirement compared to baseline (as defined as the ratio of O2 flow through the Venturi mask).	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the time to resolution of fever	Evaluation of the time to resolution of fever, defined as body temperature ≤36.6°C axilla, ≤37.8°C rectal or tympanic for at least 48 hours without antipyretics in patients with fever at baseline.	6 weeks
Evaluation of the viral load on blood and sputum for COVID-19	Evaluation of the viral load on blood and sputum for COVID-19	Before administration of sarilumab, 48 hours and 96 hours after administration
Evaluation of the plasma concentration of GM-CSF	Evaluation of the plasma concentration of GM-CSF	Pre-treatment and 96 and 120 hours post-treatment
Evaluation of the plasma concentration of Il-6	Evaluation of the plasma concentration of Il-6	Pre-treatment and 96 and 120 hours post-treatment
Evaluation of the plasma concentration of TNF-α	Evaluation of the plasma concentration of TNF-α	Pre-treatment and 96 and 120 hours post-treatment
Evaluation of the rate of progression of White Blood Cell (WBC) fraction	Evaluation of the rate of progression of WBC fraction of immature granulocytes - IG - (absolute count).	96 and 120 hours post-treatment

Collaborators and Investigators

• Sponsor: ASST Fatebenefratelli Sacco
• Investigators: Principal Investigator: Massimo Galli, Professor, University of Milan

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: May 7, 2020
• First Submitted That Met QC Criteria: May 12, 2020
• First Posted (Actual): May 13, 2020

Study Record Updates

• Last Update Posted (Actual): July 20, 2021
• Last Update Submitted That Met QC Criteria: July 19, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Coronavirus; Pandemic; Lombardy
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: COVID-SARI-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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