Efficacy and Safety of Tozorakimab in Patients Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen

Study Overview
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Brief Summary
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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.

Official Title
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A Phase III, Multicentre, Randomised, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Tozorakimab (MEDI3506) in Patients Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen

Conditions
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Viral Lung Infection and Acute Respiratory Failure

Intervention / Treatment
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* Drug: Tozorakimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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. Exclusion Criteria: Known fungal or parasitic lung infection, aspiration lung infection, lung abscess, or pulmonary sepsis. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tozorakimab<br>Approximately 2902 participants will be randomized in a 1:1 ratio. Arm 1 (n=approximately 1451) will receive a single dose of tozorakimab. | Drug: Tozorakimab<br>* Single IV dose of tozorakimab on Day 1.<br>* Other names: MEDI3506;|
| Placebo Comparator: Placebo<br>Approximately 2902 participants will be randomized in a 1:1 ratio. Arm 2 (n=approximately 1451) will receive matching placebo. | Drug: Placebo<br>* Single IV dose of matching placebo on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who die or progress to Invasive Mechanical Ventilation (IMV) / Extracorporeal Membrane Oxygen (ECMO) | 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. | by Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who die | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on all-cause mortality. | by Day 60 | 
| Number of days alive and outside of Intensive Care Unit (ICU) | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on ICU stay. | over 28 day period | 
| Number of days alive and free of supplemental oxygen | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on the duration of oxygen supplementation. | over 28 day period | 
| Time to death or progression to Invasive Mechanical Ventilation (IMV) / Extracorporeal Membrane Oxygen (ECMO) | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on prolonging time to death or IMV/ECMO. | over 28 day and 60 day period | 
| Proportion of participants who die or progress to Invasive Mechanical Ventilation (IMV) / Extracorporeal Membrane Oxygen (ECMO) | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on prolonging time to death or IMV/ECMO. | by Day 60 | 
| Time to death (all cause) | To evaluate the effect of Tozorakimab versus Placebo as add-on to Standard of Care (SoC) on prolonging time to death. | over 28 day and 60 day period | 
| Proportion of participants who die | To evaluate the effect of Tozorakimab versus Placebo as add-on to Standard of Care (SoC) on prolonging time to death. | by Day 28 | 
| Number of days alive and free of Invasive Mechanical Ventilation (IMV) / Extracorporeal Membrane Oxygen (ECMO) | To evaluate the effect of Tozorakimab versus placebo as add-on to Standard of Care (SoC) on ventilator use. | over 28 day and 60 day period | 
| Number of days alive and ventilator free | To evaluate the effect of Tozorakimab versus placebo as add-on to Standard of Care (SoC) on ventilator use. | over 28 day and 60 day period | 
| Proportion of participants with Intensive Care Unit (ICU) admission or death | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on ICU admissions. | by Day 28 | 
| Proportion of participants with Intensive Care Unit (ICU) admission or death | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on ICU admissions. | by Day 60 | 
| Proportion of participants alive and discharged | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on duration of hospitalisation. | by Day 28 | 
| Proportion of participants alive and discharged | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on duration of hospitalisation. | by Day 60 | 
| Time to discharge | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on duration of hospitalisation. | over 28 day and 60 day period | 
| Time to being off supplemental oxygen | To evaluate the effect of tozorakimab versus placebo as add-on to Standard of Care (SoC) on duration of hospitalisation. | over 28 day and 60 day period | 
| World Health Organization (WHO) 10-category ordinal Clinical Progression Scale | 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). | by Day 60 | 
| Incidence of anti-drug antibodies | To evaluate the immunogenicity (presence of tozorakimab anti-drug antibodies in blood serum) in participants with viral lung infection requiring supplemental oxygen. | over 60 day period | 
| Baseline serum interleukin-33/soluble Suppression of Tumorgenicity 2 (IL-33/sST2) complex levels relative to primary endpoint | 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). | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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