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

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ClinicalTrials.gov Identifier: NCT04386239
Recruitment Status : Recruiting
First Posted : May 13, 2020
Last Update Posted : January 20, 2021
Sponsor:
Information provided by (Responsible Party):
Stefano Rusconi, ASST Fatebenefratelli Sacco

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
COVID19 Drug: Sarilumab Prefilled Syringe Early Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Monocentric, escalation dose
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study on the Use of Sarilumab in Patients With COVID-19 Infection
Estimated Study Start Date : January 2021
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Sarilumab

Arms and Interventions
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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 Name: Sarilumab


Outcome Measures
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Primary Outcome Measures :
  1. Proportion of patients who show an improvement of the respiratory function [ Time Frame: 6 weeks ]
    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).


Secondary Outcome Measures :
  1. Evaluation of the time to resolution of fever [ Time Frame: 6 weeks ]
    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.

  2. Evaluation of the viral load on blood and sputum for COVID-19 [ Time Frame: Before administration of sarilumab, 48 hours and 96 hours after administration ]
    Evaluation of the viral load on blood and sputum for COVID-19

  3. Evaluation of the plasma concentration of GM-CSF [ Time Frame: Pre-treatment and 96 and 120 hours post-treatment ]
    Evaluation of the plasma concentration of GM-CSF

  4. Evaluation of the plasma concentration of Il-6 [ Time Frame: Pre-treatment and 96 and 120 hours post-treatment ]
    Evaluation of the plasma concentration of Il-6

  5. Evaluation of the plasma concentration of TNF-α [ Time Frame: Pre-treatment and 96 and 120 hours post-treatment ]
    Evaluation of the plasma concentration of TNF-α

  6. Evaluation of the rate of progression of White Blood Cell (WBC) fraction [ Time Frame: 96 and 120 hours post-treatment ]
    Evaluation of the rate of progression of WBC fraction of immature granulocytes - IG - (absolute count).


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 84 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04386239


Contacts
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Contact: Agostino Riva, MD 02-39042676 agostino.riva@unimi.it
Contact: Massimo Galli, Professor massimo.galli@unimi.it

Locations
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Italy
Divisione Clinicizzata di Malattie Infettive, ASST FBF-Sacco Recruiting
Milano, MI, Italy, 20157
Contact: Agostino Riva, M.D.    00390239042676    agostino.riva@unimi.it   
Sponsors and Collaborators
ASST Fatebenefratelli Sacco
Investigators
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Principal Investigator: Massimo Galli, Professor University of Milan
  Study Documents (Full-Text)

Documents provided by Stefano Rusconi, ASST Fatebenefratelli Sacco:
Study Protocol and Statistical Analysis Plan  [PDF] April 15, 2020

More Information
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Responsible Party: Stefano Rusconi, Co-investigator, ASST Fatebenefratelli Sacco
ClinicalTrials.gov Identifier: NCT04386239    
Other Study ID Numbers: COVID-SARI-001
First Posted: May 13, 2020    Key Record Dates
Last Update Posted: January 20, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Stefano Rusconi, ASST Fatebenefratelli Sacco:
Coronavirus
Pandemic
Lombardy
Additional relevant MeSH terms:
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Infection