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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

9 Jan 2023 → ongoing

Decision date (initial)

2024-02-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-507031-38-00

EudraCT number

2022-003107-15

ClinicalTrials.gov

NCT05624450

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy, Pharmacokinetic, Pharmacodynamic

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 28

Secondary objectives 5

1. 1. To evaluate the effect of tozorakimab versus placebo as add-on to standard of care on: a) all-cause mortality by Day 60 b) ICU stay c) duration of oxygen supplementation d) prolonging time to death or IMV/ECMO e) prolonging time to death f) ventilator use g) ICU admissions h) duration of hospitalisation i) clinical status as assessed by the Investigator using WHO 10-category ordinal Clinical Progression Scale by Day 60
2. 2. To evaluate the pharmacokinetics and immunogenicity of tozorakimab in participants with viral lung infection requiring supplemental oxygen.
3. 3. To evaluate the use of baseline serum biomarker levels to predict treatment response with tozorakimab versus placebo as add on to standard of care.
4. 4. To assess the safety and tolerability of tozorakimab versus placebo as add-on to standard of care.
5. 5. To evaluate the effect of tozorakimab as add on to SoC on a series of HRU endpoints.

Conditions and MedDRA coding

Severe viral lung infections

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 1. Adult participants ≥ 18 years old at the time of signing the informed consent form.
2. 2. Patients hospitalised with viral lung infection.
3. 3. 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 > 22.
4. 4. Patient remains hypoxaemic at randomisation requiring treatment with supplemental oxygen.

Exclusion criteria 4

1. 1. 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.
2. 2. Hypoxaemia caused primarily by extrapulmonary insult or by lung injury of non-infective aetiology.
3. 3. Ongoing IMV/ECMO at randomisation.
4. 4. The 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants who die or progress to IMV/ECMO by Day 28

Secondary endpoints 16

1. 1. Proportion of participants who die by Day 60
2. 2. Number of days alive and outside of ICU over 28 day period
3. 3. Number of days alive and free of supplemental oxygen over 28 day period
4. 4. Time to death or progression to IMV/ECMO
5. 5. Proportion of participants who die or progress to IMV/ECMO by Day 60
6. 6. Time to death (all cause)
7. 7. Proportion of participants who die by Day 28
8. 8. Number of days alive and free of IMV/ECMO over 28 day and 60 day period
9. 9. Number of days alive and ventilator free over 28 day and 60 day period
10. 10. Proportion of participants with ICU admission or death by Day 28 and Day 60
11. 11. Proportion of participants alive and discharged by Day 28 and Day 60
12. 12. Time to discharge
13. 13. Time to being off supplemental oxygen
14. 14. WHO CPS score rank-based comparison
15. 15. Presence of anti-drug antibodies
16. 16. Baseline serum biomarker levels relative to primary endpoint

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

14 EU/EEA countries · 113 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 116 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

17 submissions — initial application plus substantial / non-substantial modifications