EUCTR2020‐001390‐76‐IT
Trial name or title	A phase 3, randomized, open‐labeled, multi‐center study comparing clinical efficacy and safety of intravenous sarilumab plus standard of care compared to standard of care, in the treatment of patients with severe COVID‐19 pneumonia.
Methods	RCT, active‐controlled, open‐label study Date of study: June 2020 Location: Italy Phase 3
Participants	Randomised: 171 participants Inclusion criteria Age = 18 years Signed informed consent provided by the patient, or by the patient’s legally authorised 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). Virological diagnosis of SARS‐CoV‐2 infection (SARS‐CoV‐2 infection confirmed by PCR test or positive serology) Evidence of pulmonary infiltrates at CT scan or Chest Xray Oxygen saturation (SpO2) at rest without oxygen supplementation < 93% or PaO2/FiO2 < 300 at rest in patients requiring oxygen supplementation (either Venturi mask or cPAP or NIV). Evidence of hyperinflammation defined as at least 2 of the following: blood lymphocytes < 1000/mm3; ferritin > 500 ng/mL; LDH > 300 U/L; D‐dimers > 1000 ng/mL; C‐reactive protein > 3 mg/dL. 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‐CoV‐2) Men and women of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method (s) of contraception Exclusion criteria Known hypersensitivity to sarilumab or its excipients Known active infections or other clinical condition that contraindicate sarilumab and cannot be treated or solved according to the judgement of the clinician Patient being treated with immunomodulators or anti‐rejection drugs Pregnancy/lactation Neutrophils count < 500 cell/mm3 Platelets count < 50.000/mm3 ALT / AST> 5 times the upper limit of the normality Bowel diverticulitis or perforation 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 Severe hepatic dysfunction Creatinine clearance < 30 ml/min/1.73 m2 Mechanical ventilation or ECMO Enrolment in another concurrent clinical interventional study Intake of an investigational drug within 3 months
Interventions	Intervention: ·sarilumab (IV, 400 mg) Control interventions: standard of care
Outcomes	Primary outcome Time to clinical improvement (every visit) Secondary outcomes Mortality (30 days from baseline) Time to death Time to mechanical ventilation or extracorporeal membrane oxygenation Serious adverse events
Starting date	Study start date: 27 April 2020
Contact information	Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani, 0655170546, immunodeficienzevirali@inmi.it
Notes	Ongoing