Anakinra treatment to prevent respiratory failure in COVID-19

INTERVENTION: Trade Name: Kineret Product Name: Anakinra Pharmaceutical Form: Solution for injection in pre‐filled syringe Pharmaceutical form of the placebo: Solution for solution for injection Route of administration of the placebo: Subcutaneous use CONDITION: COVID‐19 ; MedDRA version: 20.0 Level: LLT Classification code 10035738 Term: Pneumonia viral NOS System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: The SAVE‐MORE is a pivotal, confirmatory, phase III randomized clinical trial (RCT) aiming to evaluate the efficacy and safety of early start of anakinra guided by suPAR in patients with LRTI by SARS‐CoV‐2 in improving the clinical state of COVID‐19 over 28 days as measured by the ordinal scale of the 11‐point WHO clinical progression scale (CPS). Primary end point(s): The primary study outcome is the comparative 5‐scale patient state evaluated from the 11‐point WHO Clinical Progression ordinal Scale (CPS) between the two arms of treatment by Day 28. This will be expressed as the distribution of the frequencies of each score of the scale in each arm of treatment by Day 28. Secondary Objective: Not applicable Timepoint(s) of evaluation of this end point: Day 28 SECONDARY OUTCOME: Secondary end point(s): The comparison of the following between the two arms of treatment:; • Change of the measure of the 11‐point of WHO Clinical Progression ordinal Scale (CPS) by Day 28 from baseline Day 1 (both absolute and relative changes) ; • Change of the measure of the 11‐point of WHO Clinical Progression ordinal Scale (CPS) by Day 14 from baseline Day 1 (both absolute and relative changes) ; • Change of the SOFA score by Day 14 from baseline Day 1 (both absolute and relative changes) ; • Change of the SOFA score by Day 7 from baseline Day 1 (both absolute and relative changes) ; • Time until discharge from hospital; • Time until discharge from the intensive care unit (this applies only for patients failing the primary outcome who will be admitted in the ICU); • Long‐term safety by Day 60; • Long‐term safety by Day 90; • Relative changes of circulating concentrations of suPAR, CRP, D‐dimers, ferritin, and IL‐6 by Day 7 from baseline Day 1; • Relative changes of circulating concentrations of suPAR, CRP, D‐dimers, ferritin, and IL‐6 by Day 4 from baseline Day 1; • Change of the viral load by Day 7 from baseline Day 1 (both absolute and relative changes); • Change of the viral load by Day 4 from baseline Day 1 (both absolute and relative changes); • Transcriptomic analysis that will also allow for lymphocyte cell subset analysis; • Proteomic analyses; • Relation of endpoints to duration of disease (from first symptoms) and timing of treatment initiation Timepoint(s) of evaluation of this end point: Days 4, 7, 14, 28, 60 and 90, at hospital discharge and at discharge from the intensive care unit INCLUSION CRITERIA: 1. Age equal to or above 18 years 2. Male or female gender 3. In case of women, unwillingness to remain pregnant during the study period. 4. Written informed consent provided by the patient. For subjects without decision‐making capacity, informed consent must be obtained from a legally designated representative following the national legislation in the Member State where the trial is planned. 5. Confirmed infection by SARS‐CoV‐2 virus 6. Findings in chest‐X‐ray or in chest computed tomography compatible with lower respiratory tract infection 7. Need for hospitalization for COVID‐19. The need for hospitalization is defined by the attending physician taking into consideration clinical presentation, requirement for supportive care, potential risk factors for severe disease, and conditions at home, including the presence of vulnerable persons in the household. 8. Plasma suPAR =6ng/ml Are the trial subjects under 18? no Number of subject