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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 (TILIA).

Phase 3
Conditions
J129 Viral pneumonia, unspecified
Viral pneumonia, unspecified
J129
Registration Number
PER-008-23
Lead Sponsor
AstraZeneca AB
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Without startig enrollment
Sex
All
Target Recruitment
0
Inclusion Criteria

Age
1.Adult participants = 18 years old at the time of signing the ICF.

Type of Participant and Disease Characteristics:
2.Patients hospitalised with viral lung infection. Note: Suspected viral aetiology is acceptable to meet this criterion.
3.Hypoxaemia requiring treatment with supplemental O2. Hypoxaemia is defined as:
?SpO2 = 90% OR
?SpO2 = 92% AND one or both of the following:
oRadiographic infiltrates by Chest X-ray/CT scan compatible with viral lung infection per investigator judgement.
oUse of accessory muscles of respiration or respiratory rate > 22/minute.
Note: Patients receiving oxygen > 6 L/min or non-invasive ventilation will be considered
to have met this inclusion criterion regardless of SpO2 levels. A documented pre-hospital
SpO2 (related to the episode) is acceptable, eg, from the ambulance report.
4.= 36 hours since admission to hospital. Refer to Section 4.3 for more details.
5.= 14 days since onset of respiratory viral infection symptoms.

Exclusion Criteria

Medical Conditions:
1Known 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.
2Hypoxaemia caused primarily by extrapulmonary insult (eg, multiorgan failure, shock, or sepsis) or by lung injury of noninfective aetiology (eg, trauma, chemical injury, etc).
3Ongoing IMV/ECMO at randomisation.
4Any comorbid condition that, in the opinion of the investigator, is likely to result in death within 3 months from randomisation.
5Anticipated recovery and discharge from the hospital within 24 hours of randomisation.
6Active tuberculosis defined as disease requiring current treatment.
7Known unstable cardiovascular disease (eg, unstable chronic heart failure NYHA III-IV, recent myocardial infarction or stroke within 3 months, uncontrolled ventricular arrhythmia, or cardiogenic pulmonary oedema which is driving the severity of the hypoxaemia, that in the investigator’s judgement may put the participant at risk or negatively affect the outcome of the study).
8Known absolute neutrophil count = 1.0 x 109/L.
9Known untreated HIV. Known history of active hepatitis B or C (treated and controlled hepatitis and HIV are allowed).
10Known history of active severe inflammatory bowel disease or colitis (including Crohn disease or ulcerative colitis).
11The following malignancies:
?Solid tumours with metastases (Stage IV).
?Lymphoma/leukaemia not in complete remission.
?Malignancies treated with chemotherapy and/or immunomodulatory drugs within the past 2 months.
12Transplant patients at risk of organ rejection, or those on long-term immunosuppressive treatment for the transplant. Treatment with corticosteroids is allowed.
13Any disorder that is not stable in the opinion of the investigator, including but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious (including risk factors for viral lung infection), endocrine, metabolic, haematological, immune, psychiatric, or major physical impairment and could:
?affect the safety of the participant throughout the study,
?influence the findings of the study or their interpretation,
?impede the participant’s ability to complete the entire duration of the study.

Prior/Concomitant Therapy:
14Use of long-term oxygen therapy for pre-existing conditions.
15Chronic treatment with TNF inhibitors, Janus kinase inhibitors or interferon-gamma. Wash-out period of 4 weeks or 5 half-lives (whichever is longer) is required prior to enrolment.
16Current treatment with any investigational medication. Wash-out period of 4 weeks or 5 half-lives (whichever is longer) is required prior to enrolment.
17Participants who have previously received tozorakimab.
18Known history of:
?anaphylaxis to any biologic therapy,
?severe reaction to any medication, including biologic agents or human gamma globulin therapy,
?allergy or reaction to any component of the study intervention formulation.

Contraception:
19Pregnant and lactating participants.
20Male participants who are sexually active with a FOCBP and participants that are FOCBP who are sexually active with a male partner, unless they agree to use highly effective contraceptive methods from enrolment throughout the study

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
The primary analysis will be conducted using a stratified Cochran-Mantel-Haenszel ?2 test, for the CVPAS, stratified by known viral positivity at randomisation (SARS-CoV-2 vs other virus versus indeterminate) and region.<br> NAME OF THE RESULT: Proportion of participants who die or progress to IMV/ECMO by Day 28<br> PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE<br> PRIMARY RESULT: During the study period
Secondary Outcome Measures
NameTimeMethod
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