Efficacy and Safety of Tozorakimab in Patients Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen (TILIA).
Scientific Title of Study
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).
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Mr Tapankumar M Shah
Designation
Senior Director, Asia Area Cluster Head, Site Management & Monitoring
Affiliation
AstraZeneca Pharma India Ltd.
Address
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore
Bangalore KARNATAKA 560045 India
Phone
9535104975
Fax
Email
Tapankumar.Shah@astrazeneca.com
Details of Contact Person Public Query
Name
Mr Tapankumar M Shah
Designation
Senior Director, Asia Area Cluster Head, Site Management & Monitoring
Affiliation
AstraZeneca Pharma India Ltd.
Address
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore
Bangalore KARNATAKA 560045 India
Phone
9535104975
Fax
Email
Tapankumar.Shah@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB 151 85 Sodertalje, Sweden
Primary Sponsor
Name
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, OuterRing Road, Bangalore – 560045,
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca AB
151 85 Sodertalje, Sweden
Countries of Recruitment
Argentina Australia Austria Brazil Bulgaria Canada Chile China Colombia Czech Republic Denmark France Germany Hong Kong Hungary India Israel Italy Japan Malaysia Mexico Peru Philippines Poland Republic of Korea Romania Saudi Arabia Slovakia South Africa Spain Sweden Taiwan Thailand Turkey United Kingdom United States of America Viet Nam
Dept of Pulmonary Medicine
Mangalam Arcade, Odhav Rd, Opposite Odhav Talav B.R.T.S Bus stop, G I D C Industrial Area, Odhav, Ahmedabad, PIN 382415
Ahmadabad GUJARAT
7575004800
parthiv@cuhindia.com
Dr Richa Giri
G.S.V.M Medical College
Department of Medicine
G.T. Road, Swaroop Nagar,
PIN 208002, India
Kanpur Dehat UTTAR PRADESH
KLES Dr. Prabhakar Kore Hospital & Medical Research Center
Dept. of General Medicine,
NH Service Road,
Basava Circle, Chikodi, Nehru Nagar,
Belagavi, PIN 590010
Belgaum KARNATAKA
9844595659
jayaprakashappajigol@gmail.com
Dr Nitesh Shah
Marengo CIMS Hospital
Dept of Pulmonary and Respiratory Medicine, Off Science City Road, Science City,
Panchamrut Bunglows II, Sola,
PIN 380060
Ahmadabad GUJARAT
9825027487
dr.nitesh.shah@maregoasia.com
Dr Arun Dewan
Max Smart Hospital
Max Smart Super Speciality Hospital, Saket (A unit of Gujarmal Modi Hospital and Research Centre for Medical Sciences) Mandir Marg, Press Enclave Road, Saket, New Delhi-110017
New Delhi DELHI
9810091290
arun.dewan@maxhealthcare.com
Dr Anand Jaiswal
Medanta - The medicity
Dept. of Respiratory & Sleep Medicine
Medanta - The medicity,
CH Baktawar Singh Rd, Medicity,
Islampur Colony, Sector 38, Gurugram,
Haryana 122001
Gurgaon HARYANA
9818237391
anand.jaiswal@medanta.org
Dr Atul Gogia
Sir Ganga Ram Hospital
Sir Ganga Ram Hospital Marg, Old Rajinder Nagar, New Rajinder Nagar, New Delhi, Delhi 110060 New Delhi DELHI
9891003450
atulgogs@gmail.com
Dr Rohit Kumar
VMMC & Safdarjung Hospital
Department of Pulmonary, Critical Care & Sleep Medicine,
VMMC & Safdarjung Hospital
NH 48, near AIIMS Hospital, Ansari Nagar West, New Delhi, Delhi 110029
New Delhi DELHI
9911218081
dr.rohitkumar@mail.com
Dr Poongulali Selvamuthu
Voluntary Health Services VHS Infectious Disease Medical Centre
Department of Infectious Disease SH 49A, Pallipattu, Tharamani, Chennai, PIN 600113
Chennai TAMIL NADU
Artemis Health Sciences Institutional Ethics Committee
Approved
Bhaktivedanta Hospital Ethics Committee Bhaktivedanta Hospital and Research
Approved
Ethics Committee GSVM MEDICAL COLLEGE
Approved
Ethics Committee Sir Gangaram Hospital
Approved
Institutional ethics committee Care Institute of Medical Sciences
Approved
Institutional Ethics Committee Gleneagles Global Hospitals
Approved
Institutional ethics committee KLE University KLE Dr.PK Hospital and MRC
Approved
Institutional Ethics Committee Bharati Vidyapeeth Deemed University
Approved
Institutional Ethics Committee SMC and GGH
Approved
Institutional ethics committee The Voluntary Health Services Multi speciality Hospital & Research Centre
Approved
Institutional ethics committee VMMC & Safdarjung
Approved
Kamineni Institutional Ethics Committee
Approved
Max Health Care Ethics Committee
Approved
Medanta Institutional Ethics Committee (MIEC)
Approved
SHREY HOSPITAL INSTITUTIONAL ETHICS COMMITTEE
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: J398||Other specified diseases of upperrespiratory tract,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Placebo
Matching volume (2 mL) to Tozorakimub and single dose given at randomisation (1-time dose)
Intervention
Tozorakimab
150 mg/mL, Single dose 300 mg (2 mL) given at randomisation (1-time dose), IV injection
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
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.
ExclusionCriteria
Details
Medical Conditions
1 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 participants condition.
2 Hypoxaemia caused primarily by extrapulmonary insult (eg, multiorgan failure, shock, or sepsis) or by lung injury of non infective aetiology (eg, trauma, chemical injury, etc).
3 Ongoing or impending IMV/ECMO at randomisation (ie, WHO Clinical Progression Scale score ≥ 7).
4 Any comorbid condition that, in the opinion of the investigator, is likely to result in death within 3 months from randomisation.
5 Anticipated recovery and discharge from the hospital within 24 hours of randomisation.
6 Active tuberculosis defined as requiring current treatment.
7 Known 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.
8 Known absolute neutrophil count ≤ 1.0 x 109/L.
9 Untreated HIV. Known history of active hepatitis B or C (treated and controlled hepatitis is allowed).
10 Known history of active severe inflammatory bowel disease or colitis (including Crohn disease or ulcerative colitis).
11 Malignancy, 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.
12 Any 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. affect the safety of the participant throughout the study,
b. influence the findings of the study or their interpretation,
c. impede the participant s ability to complete the entire duration of the study.
Prior/Concomitant Therapy
13 Use of long-term oxygen therapy for pre-existing conditions.
14 Chronic 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.
15 Current 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.
16 Participants who have previously received tozorakimab.
17 Known 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
18 Pregnant and lactating participants.
19 Male 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
20 Involvement 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.
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
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
Outcome
TimePoints
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 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 the duration of oxygen supplementation
Number of days alive and free of supplemental oxygen 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
Proportion of participants who die or progress to IMV/ECMO by Day 28
To evaluate the effect of tozorakimab versus placebo as add-on to SoC on prolonging time to death
Time to death (all cause)
Proportion of participants who die by Day 28
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
Number of days alive and ventilator free (WHO CPS score 6) 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
Proportion of participants with ICU admission or death by Day 28
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
Proportion of participants alive and discharged by Day 60
Time to discharge (time to WHO CPS score ≤ 3)
Time to being off supplemental oxygen (time to WHO CPS score ≤ 4)
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
Immunogenicity: Incidence of ADA - 60 Days
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
Target Sample Size
Total Sample Size="2352" Sample Size from India="80" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is 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.
The
primary outcome is the proportion of participants who die or progress to
invasive mechanical ventilation (IMV) / extracorporeal membrane oxygenation
(ECMO) by Day 60 (WHO clinical progression scale score ≥ 7). Study
intervention will be administered on Day 1. The participants status will
be recorded daily while in hospital. Upon discharge, the participant will be
followed up by phone on Day 14 and Day 28. Final on-site visit will be
performed on Day 60.
The study
initially plans to randomise up to approximately 2352 participants (ie,
1176 per treatment arm), although the final sample size will be determined by
when the required number of events are observed. Recruitment will continue
until approximately 375 primary endpoint events are expected for the primary
population 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.
Participants
will be randomised in a 1:1 ratio to receive a single IV injection of
tozorakimab 300 mg or matching IV injection of placebo within 36 hours
from the admission to hospital.
The study
intervention will be administered in addition to standard of care (SoC)
treatments. Study participants will continue receiving SoC based on local
guidelines throughout the study.
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.