Investigating otilimab in patients with severe coronavirus related lung disease.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1150

Inclusion Criteria

Part 1
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 requiring any of the following
- high-flow oxygen (=15L/min)
- non-invasive ventilation (NIV, CPAP, BIPAP)
- 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.

Part 2
1. Age 70 years or above 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 requiring any of the following
- high-flow oxygen (=15L/min)
- non-invasive ventilation (NIV, CPAP, BIPAP)
- 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. 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 710

Exclusion Criteria

Part 1
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) haemofiltration/dialysis, or high-dose (>0.15 µg/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.

Part 2
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) haemofiltration/dialysis, or more than one inotrope/vasopressor of any class.
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], severe renal dysfunction, acute myocardial infarction or acute cerebrovascular accident within the last 3 months), severe dementia, severe disability 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, fun

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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