Viral Lung Infection and Acute Respiratory Failure
Conditions
Keywords
Acute Respiratory Failure, Acute Respiratory Distress Syndrome, Viral lung infection, Tozorakimab, Supplemental Oxygen, IL-33, COVID-19, SARS-CoV-2, Coronavirus Infections, Virus Diseases, SARS Coronavirus, MEDI3506, Respiratory Tract Infections, Infections, Lung Diseases, Influenza
Brief summary
The purpose of this study is to evaluate the effect of tozorakimab, as an add-on to SoC in patients with viral lung infection requiring supplemental oxygen, on the prevention of death or progression to IMV/ECMO.
Interventions
DRUGTozorakimab
Single IV dose of tozorakimab on Day 1.
DRUGPlacebo
Single IV dose of matching placebo on Day 1.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult participants ≥ 18 years old at the time of signing the informed consent form. * Patients hospitalised with viral lung infection. * Hypoxaemia requiring treatment with supplemental O2. Hypoxaemia is defined as: SpO2 ≤ 90% OR SpO2 ≤ 92% AND one or both of the following: Radiographic infiltrates by CXR/CT compatible with viral lung infection per investigator judgement. Use of accessory muscles of respiration or RR (respiratory rate) \> 22. \- Patient remains hypoxaemic at randomisation requiring treatment with supplemental oxygen.
Exclusion criteria
* Known fungal or parasitic lung infection, aspiration lung infection, lung abscess, or evidence of septic shock. Bacterial co-infection is allowed, unless, in the opinion of the investigator, bacterial infection defines the severity of the participant's condition. * Hypoxaemia caused primarily by extrapulmonary insult or by lung injury of non-infective aetiology. * Ongoing IMV/ECMO at randomisation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants who die or progress to Invasive Mechanical Ventilation (IMV) / Extracorporeal Membrane Oxygen (ECMO) | by Day 28 | To evaluate the effect of tozorakimab versus placebo as an add on to Standard of Care (SoC) in participants with viral lung infection requiring supplemental oxygen on the prevention of death or progression to IMV/ECMO. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants who die | by Day 60 | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on all-cause mortality. |
| Number of days alive and outside of Intensive Care Unit (ICU) | over 28 day period | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on ICU stay. |
| Number of days alive and free of supplemental oxygen | over 28 day period | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on the duration of oxygen supplementation. |
| Time to death or progression to Invasive Mechanical Ventilation (IMV) / Extracorporeal Membrane Oxygen (ECMO) | over 28 day and 60 day period | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on prolonging time to death or IMV/ECMO. |
| Proportion of participants who die or progress to Invasive Mechanical Ventilation (IMV) / Extracorporeal Membrane Oxygen (ECMO) | by Day 60 | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on prolonging time to death or IMV/ECMO. |
| Time to death (all cause) | over 28 day and 60 day period | To evaluate the effect of Tozorakimab versus Placebo as add-on to Standard of Care (SoC) on prolonging time to death. |
| Number of days alive and free of Invasive Mechanical Ventilation (IMV) / Extracorporeal Membrane Oxygen (ECMO) | over 28 day and 60 day period | To evaluate the effect of Tozorakimab versus placebo as add-on to Standard of Care (SoC) on ventilator use. |
| Number of days alive and ventilator free | over 28 day and 60 day period | To evaluate the effect of Tozorakimab versus placebo as add-on to Standard of Care (SoC) on ventilator use. |
| Proportion of participants with Intensive Care Unit (ICU) admission or death | by Day 28 | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on ICU admissions. |
| Proportion of participants alive and discharged | by Day 28 | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on duration of hospitalisation. |
| Time to discharge | over 28 day and 60 day period | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on duration of hospitalisation. |
| Time to being off supplemental oxygen | over 28 day and 60 day period | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on duration of hospitalisation. |
| World Health Organization (WHO) 10-category ordinal Clinical Progression Scale | by Day 60 | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on clinical status as assessed by the Investigator using WHO 10-category ordinal Clinical Progression Scale (0 least severe to 10 most severe). |
| Presence of anti-drug antibodies | over 60 day period | To evaluate the immunogenicity (presence of tozorakimab anti-drug antibodies in blood serum) in participants with viral lung infection requiring supplemental oxygen. |
| Baseline serum interleukin-33/soluble Suppression of Tumorgenicity 2 (IL-33/sST2) complex levels relative to primary endpoint | Day 1 | To evaluate the use of baseline serum IL-33/sST2 complex levels (U/mL) to predict treatment response with tozorakimab versus placebo as add on to Standard of Care (SoC). |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czechia, Denmark, Egypt, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Peru, Philippines, Poland, Puerto Rico, Romania, Saudi Arabia, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed