Severe pulmonary COVID-19 (SARS-CoV-2 infection) related disease Infections and Infestations
Conditions
Interventions
This study is a multi-center, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of otilimab for the treatment of severe pulmonary COVID-19 related disease. The study
Sponsors
GlaxoSmithKline (United Kingdom)
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: 2.1. Have positive SARS-CoV-2 result (any validated test, e.g. RT-PCR [performed on an appropriate specimen; e.g. respiratory tract sample]) 2.2. AND be hospitalized due to diagnosis of pneumonia (chest X-ray or computerized tomography [CT] scan consistent with COVID-19) 2.3. AND be developing new-onset of oxygenation impairment requiring any of the following: 2.3.1. High-flow oxygen (=15 l/min) 2.3.2. Non-invasive ventilation (e.g. CPAP, BiPAP) 2.3.3. Mechanical ventilation =48 h prior to dose 2.4. AND have increased biological markers of systemic inflammation (either CRP >ULN1 or serum ferritin >ULN1). 3. No gender restriction. 4. Female participants must meet and agree to abide by the contraceptive criteria Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: 4.1. Is a woman of non-childbearing potential (WONCBP) OR 4.2. Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, during the study intervention period and for at least 60 days after the last dose of study intervention (sexual abstinence is acceptable if it is the participant’s normal practice). 4.3. If not consistently on a highly effective method of contraception during hospitalization, the participant must agree to a highly effective contraception plan if discharged before Day 60. 4.4. The investigator should evaluate potential for contraceptive method failure (e.g. noncompliance, recently initiated) in relation to the first dose of study intervention. 4.5. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) at hospital admission or before the first dose of study intervention. 4.6. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. 5. Capable of giving written informed consent. If participants are not capable of giving written informed consent, alternative consent procedures will be followed as detailed in the protocol
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 (>0.15?g/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 Note: Participants with an organ transplant are therefore excluded (except patients with corneal transplants not requiring immunosuppression). 12. History of allergic reaction, including anaphylaxis to any previous treatment with an anti-GM-CSF therapy 13. Received COVID-19 convalescent plasma within 48 hours of randomization Note: Participants who have received COVID-19 convalescent plasma but continue to worsen in the 48 hours after infusion of the convalescent plasma, in the opinion of the investigator, will become eligible for the study 14. Currently receiving chronic oral corticosteroids for a non-COVID-19 related condition in a dose higher than prednisone 10 mg or equivalent per day 15. Treatment with an investigational drug within 30 days of randomization 16. Participating in other drug clinical trials, including for COVID-19 17. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x upper limit of normal (ULN) 18. Platelets <50,000/mm³ 19. Hemoglobin =9 g/dl 20. Absolute neutrophil count (ANC) <1.5 x 109/l (neutropenia = Grade 2) 21. Estimated GFR =30 ml/min/1.73m² 22. Pregnant or breastfeeding females
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of participants alive and free of respiratory failure at Day 28. Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Number of deaths due to all causes at Day 60, taken from the medical records and as recorded in the eCRF 2. Time to number of deaths due to all causes at Day 60, taken from the medical records and as recorded in the eCRF 3. Proportion of participants alive and free of respiratory failure at Day 7. Participants alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. 4. Proportion of participants alive and free of respiratory failure at Day 14. Participants are alive and free of respiratory failure if they are in category 1, 2, 3 or 4 from the GlaxoSmithKline (GSK) modified version ordinal scale adapted from World Health Organization (WHO) scale 2020. The 8-point scale is as follows: 1) Non-hospitalized, no limitation of activity; 2) Non-hospitalized, limitation of activity; 3) Hospitalized, no oxygen therapy; 4) Hospitalized, low-flow oxygen by mask or nasal prongs; 5) Hospitalized, high-flow oxygen (=15L/min), continuous positive airway pressure (CPAP), bilevel positive airway pressure (BIPAP), non-invasive ventilation; 6) Hospitalized, intubation and mechanical ventilation; 7) Hospitalized, mechanical ventilation plus additional organ support; 8) Death. 5. Proportion of participants alive and free of respiratory failure at Day 42. Participants are alive and f | — |
Countries
Argentina, Belgium, Brazil, England, France, Japan, Netherlands, Poland, South Africa, Spain, United Kingdom, United States of America
Contacts
Public ContactAmarjit Bhachu
Outcome results
None listed