Severe pulmonary COVID-19 related disease MedDRA version: 23.0 Level: LLT Classification code 10053983 Term: Corona virus infection System Organ Class: 100000004862
Conditions
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years and =79 years at the time of obtaining informed consent. 2. Participants must: a. have positive SARS-CoV-2 result (any validated test, e.g. RT-PCR [performed on an appropriate specimen; e.g. respiratory tract sample]) b. AND be hospitalized due to diagnosis of pneumonia (chest X-ray or computerized tomography [CT] scan consistent with COVID-19) c. AND be developing new onset of oxygenation impairment defined as: requiring any of the following: 1. high-flow oxygen (=15L/min) 2. non-invasive ventilation (e.g. CPAP, BIPAP) 3. mechanical ventilation =48h prior to dose d. AND have increased biological markers of systemic inflammation (either CRP >ULN or serum ferritin >ULN). 3. No gender restriction 4. Female participants must meet and agree to abide by the contraceptive criteria detailed in the protocol. 5. Capable of giving written informed consent. If participants are not capable of giving written informed consent, alternative consent procedures will be followed. 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 440 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 360
Exclusion criteria
Exclusion criteria: 1. Progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatments, in the opinion of the investigator. 2. Multiple organ failure according to the investigator’s judgement or a Sequential Organ Failure assessment (SOFA score) >10 if in the ICU. 3. Extracorporeal membrane oxygenation (ECMO) hemofiltration/dialysis, or high-dose (>0.15µg/kg/min) noradrenaline (or equivalent) or more than one vasopressor. 4. Current serious or uncontrolled medical condition (e.g. significant pulmonary disease [such as severe COPD or pulmonary fibrosis], heart failure [NYHA class III or higher], significant renal dysfunction, acute myocardial infarction or acute cerebrovascular accident within the last 3 months) or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study. 5. Untreated systemic bacterial, fungal, viral, or other infection (other than SARS-CoV-2). 6. Known active tuberculosis (TB), history of untreated or incompletely treated active or latent TB, suspected or known extrapulmonary TB. 7. Known HIV regardless of immunological status. 8. Known HBsAg and/or anti-HCV positive. 9. Currently receiving radiotherapy, chemotherapy or immunotherapy for malignancy. 10. Received monoclonal antibody therapy (e.g. tocilizumab, sarilumab) within the past 3 months prior to randomization, including intravenous immunoglobulin or planned to be received during the study. 11. Received immunosuppressant therapy including but not limited to cyclosporin, azathioprine, tacrolimus, mycophenolate, JAK inhibitors (e.g. baricitinib, tofacitinib, upadacitinib) within the last 3 months prior to randomization or planned to be received during the study. 12. History of allergic reaction, including anaphylaxis to any previous treatment with an anti- GM-CSF therapy. 13. Currently receiving chronic oral corticosteroids for a non-COVID-19 related condition in a dose higher than prednisone 10 mg or equivalent per day. 14. Treatment with an investigational drug within 30 days of randomization. 15. Participating in other drug clinical trials, including for COVID-19. 16. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x upper limit of normal (ULN) 17. Platelets <50,000/mm3 18. Hemoglobin =9 g/L 19. Absolute neutrophil count (ANC) <1.5 x 109/L (neutropenia = Grade 2) 20. Estimated GFR =30 mL/min/1.73m2 21. Pregnant or breastfeeding females.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of otilimab IV versus placebo. ;Secondary Objective: To compare the efficacy of otilimab IV versus placebo. To compare the safety and tolerability of otilimab IV versus placebo. ;Primary end point(s): Participants alive and free of respiratory failure;Timepoint(s) of evaluation of this end point: Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - All-cause mortality at Day 60 - Time to all-cause mortality up to Day 60 - Participants alive and free of respiratory failure at Day 7, 14, 42, and 60 - Time to recovery from respiratory failure up to Day 28 - Participants alive and independent of supplementary oxygen at Day 7, 14, 28, 42, and 60 - Time to last dependence on supplementary oxygen up to Day 28 - Admission to ICU up to Day 28 - Time to final ICU discharge up to Day 28 - Time to final hospital discharge up to Day 28 - Occurrence of adverse events (AEs) [up to Day 60] - Occurrence of serious adverse events (SAEs) [up to Day 60];Timepoint(s) of evaluation of this end point: Various timepoints up to Day 60. | — |
Countries
Argentina, Belgium, Brazil, Canada, Chile, France, Japan, Mexico, Netherlands, Poland, South Africa, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactGSK Clinical Support HelpDesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed