Evaluate the efficacy and safety of Itolizumab in hospitalised patients with COVID-19 requiring oxygen therapy
Scientific Title of Study
A Phase 3, multi-centre, randomised, double-blind, placebo-controlled, study to evaluate the efficacy and safety of Itolizumab in hospitalised patients with COVID-19 requiring oxygen therapy
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
BIO-ITOLIZ-304, 2.0, Dated 29-Sep-2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Vivek G
Designation
Medical superintendent and assistant professor
Affiliation
Rajarajeswari Medical College and Hospital
Address
Room no 1130, Dept of Pulmonary medicine Ground Floor,202, Kambipura, Mysore Road, Bangalore – 560074, Karnataka
Bangalore KARNATAKA 560074 India
Phone
09739701000
Fax
Email
vivek.g27@gmail.com
Details of Contact Person Scientific Query
Name
Dr Subramanian L
Designation
Associate Vice President
Affiliation
Biocon Biologics Limited
Address
Biocon house, Electronic City, Bangalore, 560100
Bangalore KARNATAKA 560100 India
Phone
08067751323
Fax
Email
subramanian.l101@biocon.com
Details of Contact Person Public Query
Name
Sivakumar Vaidyanathan
Designation
General Manager
Affiliation
Biocon Biologics Limited
Address
Biocon house, Electronic City, Bangalore, 560100
Bangalore KARNATAKA 560100 India
Phone
08067756775
Fax
Email
sivakumar.vaidyanathan@biocon.com
Source of Monetary or Material Support
Biocon Limited, 20th KM Electronic City, Bangalore 560100
Primary Sponsor
Name
Biocon Limited
Address
Biocon Limited, 20th KM, Hosur Road, Electronic City,
Bengaluru- 560100, Karnataka, India
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Brazil India
Sites of Study
No of Sites = 10
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Atul Jindal
All India Institute of medical Sciences
Department: Department of Pediatrics.
Division: 1st floor
Room /Chamber No.: Room no. 1111,
Tatibandh, GE Road, Raipur - 492099,
Chhattisgarh
Raipur CHHATTISGARH
8224014667
dratuljindal@gmail.com
Dr Giridhar Patil
Belagavi Institute Of Medical Sciences
Department: Department of General Medicine
Division: Ground floor
Room /Chamber No.: Opd No 42
, Dr B R Ambedkar Road Belgaum
Belagavi (Belgaum) - 590001, Karnataka
Belgaum KARNATAKA
9845111575
Giridharpatil20@gmail.com
Dr ME Mohan
BGS Global Institute of Medical Sciences and hospital
Department: Department of General Medicine
Division: Unit 1
Room /Chamber No.: Dean and Principal chamber, #67
, BGS GIMS, Kengeri, Bangalore-560060 Bangalore KARNATAKA
9980006191
drmohanbgsresearch@gmail.com
Dr Nischal V Yalgi
Global Hospital and Research Institute
Department: Department of Medicine
Division: Ground floor
Room /Chamber No.: OPD no- 4
,Institute. OFF sinhgad Road, Near Dattawadi Polic Chowki, Dattawadi,Pune. Pune MAHARASHTRA
09168764422
drrakeshwaghmare@gmail.com
Dr Yandrapati Gnana Sundara Raju
King George Hospital
Department: Department of General Medicine
Division: 1st floor
Room /Chamber No.: 02
, Rajendraprasad Ward,Maharanipeta,Visakhapatnam-530002,Andhrapradesh,India. Visakhapatnam ANDHRA PRADESH
09573606609
drysundarrajuresearch@gmail.com
Dr Nirhali Sonali Chandrakant
Lifepoint Multispeciality Hospital,
Department: Department of Medicine
Division: NA
Room /Chamber No.: 1
14s/1, Mumbai Banglore Highway, Near Hotel Sayaji, wakad, Pune-411057,Maharashtra, India. Pune MAHARASHTRA
07502613126
sonalinirhali26@gmail.com
Dr Anand Marutirao Nikalje
MGM Medical College & Hospital
Department: Department of General Medicine
Division: Ground floor/ Basement
Room /Chamber No.: NA
, N-6, CIDCO Aurangabad - 431003, Maharashtra Aurangabad MAHARASHTRA
9822496190
anandnikalje@rediffmail.com
Dr Ashish Omprakash Goyal
Orchid Speciality Hospital
Department: Department of Pulmonology
Division: 1st floor
Room /Chamber No.: NA
, Sr.No.282/3/3, L-Square Porwal Road,
Dhanori Jakat Naka, Longaon,
Pune-411047, Maharashtra
Pune MAHARASHTRA
9372433824
ashish_critical@yahoo.co.in
Dr Vivek G
Rajarajeswari Medical College and Hospital
Room no 1130, Dept of Pulmonary medicine Ground Floor,202, Kambipura, Mysore Road, Bangalore – 560074, Karnataka Bangalore KARNATAKA
09739701000
vivek.g27@gmail.com
Dr Rakesh D Waghmare
Yashwantrao Chavan Memorial Hospital,
Department: Department of Pulmonary Medicine,YCM Hospital Road, Sqnt tukaram Nagar, Pimpri Colony, Pune Pune MAHARASHTRA
09657746968
drnischalyalgi@gmail.com
Details of Ethics Committee
No of Ethics Committees= 11
Name of Committee
Approval Status
BGS Global Institute of Medical Science, Institutional Ethics Committee, Department of Community Medicine, Kengeri ,Bangalore South Karnataka
Approved
Ethics Committee of BMCRI Bangalore Medical College and Research Institute
Submittted/Under Review
IEC King George Hospital King George hospital, Visakhapatnam
Submittted/Under Review
Institutional Ethics Committee BIMS Belagavi Institute of Medical Sciences, Belgaum
Submittted/Under Review
Institutional Ethics Committee Rajarajeswari Medical College and Hospital, Mysore Road, Bengaluru Karnataka
Submittted/Under Review
Institutional Ethics Committee Yashwantrao Chavan Memorial Hospital, Pune Maharashtra
Saikrupa Hospital Institutional Ethics Committee Saikrupa Hospital, Pune Maharashtra
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere, (2) ICD-10 Condition: J70||Respiratory conditions due to other external agents,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Itolizumab
Itolizumab is presented as a sterile, white to pale yellow, preservative-free lyophilised cake in single-use 6R LYO (lyophilisation) glass vials stoppered with LYO stoppers and sealed with flip-off seals. Reconstitution with 1.1 mL of sterile water for injection (SWFI) yields a solution containing 100 mg/mL of itolizumab.
It is administered as single dose of 1.6 mg/kg given as an Intravenous (IV) infusion on Day 1.
The infusion must be initiated at 25 mL/h for the first hour. If well tolerated it can be increased to 50 mL/h to infuse the remaining amount. The infusion is to be completed over 6 hours.
Comparator Agent
Placebo
The Placebo is presented as a sterile, colourless to pale yellow preservative-free solution in identical glass vials as the test drug.
The single infusion of placebo will be administered. infusion will be initiated at 25 mL/h for the first hour. If well tolerated it can be increased to 50 mL/h to infuse the remaining amount. The infusion is to be completed over 6 hours.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1 Male or female adults above ≥18 years.
2 Informed consent for participation in the study by patient or their legally acceptable representative.
3 Hospitalised patients with COVID-19 infection receiving systemic steroids with scores 5 or 6 on 8-point clinical scale (hospitalised and requiring supplemental oxygen / requiring non-invasive ventilation or use of high-flow oxygen devices but not on invasive mechanical ventilation)
4 An inflammatory, phenotype defined by a body temperature greater than 38 °C / 100.4 °F anytime during the last 2 days, OR increased markers of inflammation (CRP ≥ 3 ULN as per local lab) at screening.
5 A confirmed virological diagnosis of SARS-CoV2 infection with RT-PCR
6 Patients with no known history of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV).
7 Women of childbearing potential (WOCP) with negative pregnancy test or are not breastfeeding at screening.
8 Males and WOCP agreeing to use adequate contraception (e.g., double barrier contraception) for 130 days from randomisation.
ExclusionCriteria
Details
1 Known severe allergic reactions to monoclonal antibodies.
2 Has active tuberculosis or known history of inadequately treated tuberculosis or latent tuberculosis(based on the the guidance given in protocol on excluding tuberculosis patients).
3 Known active systemic or pulmonary bacterial, fungal or viral (other than SARS-CoV-2) infection at the time of randomisation
4 In the opinion of the investigator, progression to death is highly probable, irrespective of the provision of treatments.
5 Patient receiving IMV at the time of randomisation or in the opinion of investigator, progression to IMV is highly probable in next 24 hours.
6 Patient receiving oral anti-rejection or immune-suppressive drugs regularly in the last 3 months prior to screening.
7 Participating in another clinical study of an investigational product and/or received an investigational product within 30 days or within 5 half-lives prior to randomisation.
8 Patients treated with IL-6 inhibitors, example: tocilizumab or other biologics with anti-inflammatory action (e.g., TNF-α inhibitors, anti-IL17A) or bevacizumab or JAK inhibitors (e.g. Baricitinib, Tofacitinib) or immunoglobulin for COVID-19 including other immunomodulatory biologic drugs with a positive opinion for emergency use or for compassionate use.
9 Requires renal dialysis, either acute or chronic, at the time of randomisation
10 Any serious inherited disorder, medical condition or abnormality of clinical laboratory tests that, in the investigator’s judgement, precludes the patient’s safe participation in and completion of the study.
11 Absolute neutrophil count<1000/mm³
12 Platelet count <50,000/mm³
13 Absolute Lymphocyte count<500/mm³
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Clinical composite endpoint comprising of:
1 Mortality at Day 28
2 Clinical deterioration, defined as progression to a higher ordinal score from enrolment scores of 5 or 6 during the period of 28 days.
3 Time to recovery by Day 28, defined as time to get to a score of 3 or below in the 8-point ordinalscale plus sustained recovery.
1. Day 1 through Day 28
2. Day 1 through Day 28
3. Day 1 through Day 28
Secondary Outcome
Outcome
TimePoints
Key Secondary Endpoint:-
Clinical composite endpoint comprising of :
1. Mortality at Day 90.
2. Clinical deterioration, defined as progression to a higher ordinal score from enrolment score of 5 or 6 during the period of 90 days.
3. Time to recovery, defined as time to get to a score of 3 or below in the 8-point ordinal scale plus sustained recovery.
Day 90
Secondary Endpoints:-
1.Mortality by Day 28, Day 60 and Day 90.
2.Time from randomisation to sustained recovery, defined as time to get to a score of 3 or below in the COVID-19 8-point ordinal scale plus sustained recovery.
Day 1 through Day 90
3. Proportion of patients with clinical improvement (defined as either an improvement of ≥2 points on a COVID-19 8-point ordinal scale or discharge from the hospital, whichever comes first) over time.
Day 1 through Day 90
4. Cumulative rate of patients alive and without IMV by Day 90 from randomisation
Day 1 through Day 90
5. Cumulative rate of patients going to IMV by Day 90 from randomisation.
Day 1 through Day 90
6. Duration of hospitalisation.
from randomisation up to patients discharge - Days of hospitalisation
7. Time to independence from oxygen therapy in days.
from randomisation up to Day 90
8. Change from baseline in IL-6 and TNF-α.
Baseline, 48 hours post dose, at Day 7 and then weekly until discharge
9, Change from baseline in levels of inflammatory markers like CRP, serum ferritin, D-dimer and LDH.
Baseline, 48 hours post dose, at Day 7 and then weekly until discharge
10. Incidence, nature, severity of AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) and causality of AEs.
Day 1 through Day 28 and up to Day 90
Target Sample Size
Total Sample Size="400" Sample Size from India="280" 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 multi-centre, two-arm, double-blind, placebo-controlled, randomised, clinical trial to evaluate the efficacy and safety of Itolizumab in hospitalised patients with COVID-19 requiring oxygen therapy. The study consists of a Screening period (up to 2 days), Treatment period (up to 28 days from first dose of Itolizumab/placebo) and an Extended follow-up period of up to 90 days from first dose.
Patients will be screened for up to 2 days prior to Day 1 for eligibility. About 400 eligible patients will be randomised on Day 1 in a 1:1 ratio to Treatment Arm A (Itolizumab + Standard of Care) or Treatment Arm B (Placebo + Standard of Care). Randomisation will be stratified by age, by the baseline disease severity. Patients randomised to Treatment Arm A will be administered study drug Itolizumab 1.6 mg/kg (+Standard of Care) on Day 1 via IV infusion, whereas those randomised to Treatment Arm B will be administered placebo (+Standard of Care).
All patients will receive Standard of Care as per institutional practice throughout the study including whenever appropriate steroids, antithrombotics, antivirals and antimicrobials/antibiotics. Patients will be monitored for efficacy and safety through Day 28 and followed up till Day 90.