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Trial record 4 of 10 for:    Coronavirus | sarilumab

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 : July 20, 2021
Sponsor:
Information provided by (Responsible Party):
Stefano Rusconi, ASST Fatebenefratelli Sacco

Tracking Information
First Submitted Date  ICMJE May 7, 2020
First Posted Date  ICMJE May 13, 2020
Last Update Posted Date July 20, 2021
Actual Study Start Date  ICMJE January 1, 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2020)
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).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2020)
  • 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.
  • 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
  • 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
  • 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
  • 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
  • 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).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study on the Use of Sarilumab in Patients With COVID-19 Infection
Official Title  ICMJE Pilot Study on the Use of Sarilumab in Patients With COVID-19 Infection
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.
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  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
Monocentric, escalation dose
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE COVID19
Intervention  ICMJE 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
Study Arms  ICMJE 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.
Intervention: Drug: Sarilumab Prefilled Syringe
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 12, 2020)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 84 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Agostino Riva, MD 02-39042676 agostino.riva@unimi.it
Contact: Massimo Galli, Professor massimo.galli@unimi.it
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04386239
Other Study ID Numbers  ICMJE COVID-SARI-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Stefano Rusconi, ASST Fatebenefratelli Sacco
Study Sponsor  ICMJE ASST Fatebenefratelli Sacco
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Massimo Galli, Professor University of Milan
PRS Account ASST Fatebenefratelli Sacco
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP