Covid-19 coronavirus infection MedDRA version: 20.1 Level: HLT Classification code 10047468 Term: Viral lower respiratory tract infections System Organ Class: 100000004855
Conditions
Interventions
Trade Name: sarilumab
Product Name: sarilumab
Product Code: [-]
Pharmaceutical Form: Solution for injection
INN or Proposed INN: sarilumab
CAS Number: 1189541-98-7
Current Sponsor code: -
Concentratio
Sponsors
ISTITUTO NAZIONALE PER LE MALATTIE INFETTIVE "LAZZARO SPALLANZANI"
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria: 1. Age = 18 years 2. Signed informed consent provided by the patient, or by the patient’s legally authorized representative(s), as applicable. Orally provisions could be considered in emergency conditions if deemed necessary by the investigator (signature of the informed consent will occur if and as soon as clinical conditions improve). 3. Virological diagnosis of SARS-CoV-2 infection (SARS-CoV-2 infection confirmed by PCR test or positive serology) 4. Evidence of pulmonary infiltrates at CT scan or Chest XRay 5. Oxygen saturation (SpO2) at rest without oxygen supplementation 500ng/mL; iii. LDH > 300 U/L; iv. D-Dimers > 1000 ng/mL v. C-reactive protein > 3 mg/dL 7. Indication to start antiviral therapy with either hydroxychloroquine or lopinavir/ritonavir as regular clinical practice (or patients who have already started/finished antiviral therapy for SARS-CoV2) 8. Men and women of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Appendix F. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 71 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: Exclusion criteria: 1. Known hypersensitivity to sarilumab or its excipients 2. Known active infections or other clinical condition that contraindicate sarilumab and cannot be treated or solved according to the judgement of the clinician 3. Patient being treated with immunomodulators or anti-rejection drugs 4. Pregnancy/lactation 5. Neutrophils count 5 times the upper limit of the normality 8. Bowel diverticulitis or perforation 9. Existence of any life-threatening co-morbidity or any other medical condition which, in the opinion of the investigator, makes the patient unsuitable for inclusion. 10. Severe hepatic dysfunction 11. Creatinine clearance < 30 ml/min/1.73 m2 12. Mechanical ventilation or ECMO 13. Enrolment in another concurrent clinical interventional study 14. Intake of an investigational drug within 3 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of sarilumab, combined with standard of care, in patients affected by severe COVID-19 pneumonia.;Secondary Objective: To evaluate the effect of sarilumab on survival To evaluate the effect of sarilumab on clinical evolution To evaluate the effect of sarilumab on lung function To evaluate the effect of sarilumab on hyperinflammation parameters To evaluate the effect of sarilumab on other relevant laboratory parameters To evaluate the effect of sarilumab on radiological response To evaluate the effect of sarilumab on virological response To evaluate the effect of sarilumab on duration of hospitalization To describe safety profile of sarilumab;Primary end point(s): The primary end point was the time to clinical improvement, defined as the time from receiving the first dose of drug to an improvement of two points (from the status at baseline) on a 7-point category ordinal scale. The 7-point category ordinal scale consisted of the following categories: 1.not hospitalized with resumption of normal activities; 2.not hospitalized, but unable to resume normal activities; 3.hospitalized, not requiring supplemental oxygen; 4.hospitalized, requiring supplemental oxygen; 5.hospitalized, requiring noninvasive mechanical ventilation (CPAP or NIV); 6.hospitalized, requiring ECMO, invasive mechanical ventilation, or both; 7.death.;Timepoint(s) of evaluation of this end point: Every visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of the study are: • Mortality rate within 30 days from baseline; • Time from treatment initiation to death • Time to mechanical ventilation or extracorporeal membrane oxygenation (ECMO) • Time to non-invasive ventilation (in patients requiring only supplemental oxygen with venturi mask or not requiring oxygen at baseline) • Time to increase in PaO2/FiO2 of 50 or greater compared to the nadir PaO2/FiO2 for at least 48 hours; • Days of hypoxemia (SpO2 36.6°C [axilla], or >37.2 °C [oral], or >37.8°C [rectal or tympanic]) • Change from baseline in lymphocyte count, ferritin, D-dimer, LDH, C-reactive protein • Change from baseline in inflammatory cytokines (IL1b, IL-6, IL-8, TNF-a) levels quantified by automated ELISA assay. • Change from baseline in differentiation and activation profile of CD4 and CD8 T cells analysed by flow cytometry. • Evolution from baseline of TLR expression and cytokines production by lymphocytes and monocytes tested by flow cytometry • Change from baseline in platelet count, fibrinogen creatinine • Improvement of CT scan findings repeated within 15 days from baseline • Proportion of patients achieving confirmed negative nasopharyngeal swabs (2 negative swabs within 24 hours) • Evolution of SARS-CoV2 serology • Days of hospitalization among survivors • Proportion of patients discharged hospital • Time to hospital discharge • Serious adverse events (including severe bacterial or fungal infections) • Treatment-emergent laboratory abnormalities;Timepoint(s) of evaluation of this end point: To see the study protocol | — |
Countries
Italy
Contacts
Public ContactImmunodeficienze virali
Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani
Outcome results
None listed