Efficacy and Safety of Tozorakimab in Patients Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen (TILIA).

Phase 3

Recruiting

• Conditions: Other specified diseases of upperrespiratory tract,

• Registration Number: CTRI/2023/09/058035
• Lead Sponsor: AstraZeneca Pharma India Ltd

Brief Summary

This is a Phase III,Multicentre, Randomised, Double‑blind, Parallel‑group, Placebo‑controlled Studyto Evaluate the Efficacy and Safety of Tozorakimab (MEDI3506) in PatientsHospitalised for Viral Lung Infection Requiring Supplemental Oxygen.

Theprimary outcome is the proportion of participants who die or progress toinvasive mechanical ventilation (IMV) / extracorporeal membrane oxygenation(ECMO) by Day 60 (WHO clinical progression scale score ≥ 7). Studyintervention will be administered on Day 1. The participants status willbe recorded daily while in hospital. Upon discharge, the participant will befollowed up by phone on Day 14 and Day 28. Final on-site visit will beperformed on Day 60.

 The studyinitially plans to randomise up to approximately 2352 participants (ie,1176 per treatment arm), although the final sample size will be determined bywhen the required number of events are observed. Recruitment will continueuntil approximately 375 primary endpoint events are expected for the primarypopulation or until after an interim analysis has triggered an early stop.Randomisation will be stratified by known viral positivity at randomisation(SARS‑CoV‑2 versus other virus versus indeterminate), and region.

Participantswill be randomised in a 1:1 ratio to receive a single IV injection oftozorakimab 300 mg or matching IV injection of placebo within 36 hoursfrom the admission to hospital.

The studyintervention will be administered in addition to standard of care (SoC)treatments. Study participants will continue receiving SoC based on localguidelines throughout the study.

To evaluate theeffect of tozorakimab versus placebo as add on to SoC in participants withviral lung infection requiring supplemental oxygen on the prevention of deathor progression to IMV/ECMO by Day 60.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-10-24
• Last Update Posted: 2025-04-25

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 2352

Inclusion Criteria

• 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, consistent with WHO Clinical Progression Scale for Disease Progression score of 5 and 6.
• Note: Hypoxemia is defined as SpO2 ≤ 94% on room air at screening, or documented SpO2 ≤ 94% prior to initiation of oxygen therapy.
• Patients receiving oxygen > 6 L/min or non-invasive ventilation will be considered to have met this inclusion criterion regardless of SpO2 levels.
• 4.≤ 36 hours since admission to hospital.
• 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 participants condition.
• 2Hypoxaemia caused primarily by extrapulmonary insult (eg, multiorgan failure, shock, or sepsis) or by lung injury of non infective aetiology (eg, trauma, chemical injury, etc).
• 3Ongoing or impending IMV/ECMO at randomisation (ie, WHO Clinical Progression Scale score ≥ 7).
• 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 requiring current treatment.
• 7Known unstable cardiovascular disease (eg, unstable chronic heart failure NYHA III-IV, recent myocardial infarction or stroke within 3 months, or uncontrolled ventricular arrythmia) 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.
• 9Untreated HIV.
• Known history of active hepatitis B or C (treated and controlled hepatitis is allowed).
• 10Known history of active severe inflammatory bowel disease or colitis (including Crohn disease or ulcerative colitis).
• 11Malignancy, current or within the past 5 years, except for adequately treated non invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma in situ treated with apparent success more than one year prior to enrolment.
• 12Any 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: a.
• influence the findings of the study or their interpretation, c.
• impede the participant s ability to complete the entire duration of the study.
• 14Chronic 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.
• 15Current treatment with any investigational medication.
• Wash-out period of 4 weeks or 5 half-lives (whichever is longer) is required prior to prior to enrolment.
• 17Known history of: a.
• anaphylaxis to any other biologic therapy, b.
• severe reaction to any medication including biologic agents or human gamma globulin therapy, c.
• allergy or reaction to any component of the study intervention formulation.
• Contraception 18Pregnant and lactating participants.
• 19Male 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 and until at least 14 weeks after last dose of IP.
• Other Exclusions 20Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Inability of the participant to understand and/or comply with study procedures and/or attend all telephone calls and follow-up visit in the opinion of the investigator.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate the effect of tozorakimab versus placebo as add on to SoC in participants with viral lung infection requiring supplemental oxygen on the prevention of death or progression to IMV/ECMO by Day 60	Proportion of participants who die or | progress to IMV/ECMO by Day 60 (WHO CPS score ≥ 7)

Secondary Outcome Measures

Name	Time	Method
To evaluate the effect of tozorakimab versus placebo as add-on to SoC on ventilator use	Number of days alive and free of IMV/ECMO (WHO CPS score 7) over 60 day period
To evaluate the effect of tozorakimab versus placebo as add-on to SoC on ICU admissions	Proportion of participants with ICU admission or death by Day 60
To evaluate the use of baseline IL-33/sST2 levels to predict treatment response with tozorakimab versus placebo as add on to SoC	Baseline serum IL-33/sST2 relative to primary endpoint - 60 Days
To evaluate the effect of tozorakimab versus placebo as add-on to SoC on ICU stay	Number of days alive and outside of ICU over 60 day period
To evaluate the effect of tozorakimab versus placebo as add-on to SoC on prolonging time to death or IMV/ECMO	Time to death or progression to IMV/ECMO
To evaluate the effect of tozorakimab versus placebo as add-on to SoC on duration of hospitalisation	Proportion of participants alive and discharged by Day 28
To evaluate the effect of tozorakimab versus placebo as add-on to SoC on all-cause mortality by Day 60	Proportion of participants who die by Day 60
To evaluate the effect of tozorakimab versus placebo as add-on to SoC on the duration of oxygen supplementation	Number of days alive and free of supplemental oxygen over 60 day period
To evaluate the effect of tozorakimab as add-on to SoC on clinical status as assessed by the Investigator using WHO 10-category ordinal Clinical Progression Scale by Day 60	WHO Clinical Progression Scale rank-based comparison - 60 Days
To evaluate the PK and immunogenicity of tozorakimab in participants with viral lung infection requiring supplemental oxygen	PK: Serum tozorakimab concentrations
To evaluate the effect of tozorakimab versus placebo as add-on to SoC on prolonging time to death	Time to death (all cause)

Trial Locations

Locations (12)

Artemis Hospital; 🇮🇳 Gurgaon, HARYANA, India

Bhakti Vedanta Hospital and Research Institute; 🇮🇳 Mumbai, MAHARASHTRA, India

Bharati Vidyapeeth (Deemed to be University); 🇮🇳 Pune, MAHARASHTRA, India

Central United Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

Gleneagles Aware Hospitals; 🇮🇳 Hyderabad, TELANGANA, India

KLES Dr. Prabhakar Kore Hospital & Medical Research Center; 🇮🇳 Belgaum, KARNATAKA, India

Marengo CIMS Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

Max Smart Hospital; 🇮🇳 Delhi, DELHI, India

Medanta - The medicity; 🇮🇳 Gurgaon, HARYANA, India

Sir Ganga Ram Hospital; 🇮🇳 Delhi, DELHI, India

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Artemis Hospital

🇮🇳Gurgaon, HARYANA, India

Dr Reshma Tewari

Principal investigator

9958402254

reshma@artemishospitals.com