MATIS: Phase 2/3, Randomised, Open-Label, Single-Site, Multi-Arm Trial of Ruxolitinib Plus Best Supportive Treatment (BST) versus Fostamatinib Plus BST versus BST for COVID-19 pneumonia

INTERVENTION: Trade Name: Tavlesse® Product Name: Tavlesse® Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: fostamatinib disodium hexahydrate Other descriptive name: fostamatinib Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐150 Trade Name: Jakavi® Product Name: Jakavi® Pharmaceutical Form: Tablet INN or Proposed INN: Ruxolitinib Other descriptive name: INCB018424 phosphate, INC424, ruxolitinib phosphate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐10 CONDITION: COVID‐19 pneumonia Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: • Determine the efficacy of RUX and FOS to reduce the proportion of hospitalised patients progressing from mild to severe COVID‐19 pneumonia Primary end point(s): The primary endpoint is progression from mild to severe COVID‐19 pneumonia within 14 days in hospitalised patients. Patients are recruited at a WHO COVID‐19 Severity Score of 3 and 4 and the primary endpoint is the comparison of patients whose COVID‐19 pneumonia progresses to a severity score ? 5 on the modified WHO Ordinal Scale. Specifically, the primary endpoint is met when the following are recorded within 14 days:; ; ‐ Death; ; ‐ Requirement for invasive ventilation; ; ‐ Requirement for non‐invasive ventilation including CPAP ; ; ‐ O2 saturation < 90% on =60% inspired oxygen Secondary Objective: 1. Determine the efficacy of RUX or FOS to reduce mortality ; 2. Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation or ECMO ; 3. Determine the efficacy of RUX or FOS to reduce the need for non‐invasive ventilation ; 4. Determine the efficacy of RUX or FOS to reduce the proportion of patients suffering significant oxygen desaturation; 5. Determine the efficacy of RUX or FOS to reduce the need for renal replacement therapy ; 6. Determine the efficacy of RUX and FOS to reduce the severity on COVID19 pneumonia [graded by a modified WHO Ordinal Scale]; 7. Determine the efficacy of RUX or FOS to reduce the level of inflammatory biomarkers ; 8. Determine the efficacy of RUX or FOS to reduce duration of hospital admission ; 9. Evaluate the safety of RUX and FOS for COVID19 pneumonia; Timepoint(s) of evaluation of this end point: Day 14. SECONDARY OUTCOME: Secondary end point(s): 1. Determine the efficacy of ruxolitinib or fostamatinib to reduce mortality; ; 2. Determine the efficacy of ruxolitinib or fostamatinib to reduce the need for invasive ventilation and/or extra corporeal membrane oxygenation (ECMO) ; ; 3. Determine the efficacy of ruxolitinib or fostamatinib to reduce the need for non‐invasive ventilation including continuous positive airway pressure (CPAP) or high flow nasal oxygen ; ; 4. Determine the efficacy of ruxolitinib or fostamatinib to reduce the proportion of patients suffering clinically significant oxygen desaturation; ; 5. Determine the efficacy of ruxolitinib or fostamatinib to reduce the need for renal replacement therapy; ; 6. Determine the efficacy of ruxolitinib or fostamatinib to improve the severity of COVID‐19 pneumonia on a modified WHO COVID‐19 Ordinal Scale ; ; 7. Determine the efficacy of ruxolitinib or fostamatinib to reduce blood ferritin, CRP, LDH and D‐dimer ; ; 8. Determine the efficacy of ruxolitinib or fostamatinib to reduce duration of hospital admission ; ; 9. Evaluate the safety of ruxolitinib and fostamatinib for COVID‐19 pneumonia Timepoint(s) of evaluation of this end point: Days 14 and 28. INCLUSION CRITERIA: 1. Patients age = 18 years at screening 2. Hospitalisation with COVID‐19 pneumonia AND ‐ SARS‐CoV2 infection (clinically suspected OR laboratory confirmed) AND ‐ Radiological change consistent with COVID‐19 disease 3. Grade 3 or 4 severity (WHO COVID‐19 Ordinal Scale) 4. C‐reactive protein (CRP) =50mg/L 5. Informed consent from patient or professional representative 6. No medical history that might, in the opinion of the responsible clinician, put the patient at significant risk if he/she were to participate in the trial 7. Agreement to abstain from sexual intercourse or use contraception that is >99% effective for all participants of childbearing potential for 42 days 8. For male participants, agreement to abstain from sperm donation for 42 days 9. Non‐English speakers will be able to join the study. If patients are unable to understand verbal or written information in English ‐ hospital transl