CTRI Number	CTRI/2020/05/024959 [Registered on: 01/05/2020] Trial Registered Prospectively
Last Modified On:	21/08/2020
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study	Drug Biological
Study Design	Randomized, Parallel Group, Active Controlled Trial
Public Title of Study	Efficacy and Safety of Itolizumab in COVID-19 Complications
Scientific Title of Study	A Multi-Centre, Open label, Two Arm Randomized, Pivotal Phase 2 Trial to Study the Efficacy and Safety of Itolizumab in COVID-19 Complications
Secondary IDs if Any Modification(s)	Secondary ID  Registry  ITOLI-C19-02-I-00, V3.0, 09/04/2020  Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)	Name  Dr Millind Nadkar  Address  Seth G S Medical College and KEM Hospital, Parel Mumbai 400012 Mumbai MAHARASHTRA 400012 India  Phone     Fax     Email  milindnadkar@yahoo.com
Details Contact Person Scientific Query	Name  Dr Subramanian Loganathan  Address  Biocon Biologic India Limited, Biocon House, Semicon Park Electronics City Phase 2 Bangalore 560100 Karnataka India Bangalore KARNATAKA 560100 India  Phone  08028085305   Fax  08028085000   Email  subramanian.l101@biocon.com
Details Contact Person Public Query	Name  Sivakumar Vaidyanathan  Address  Biocon Biologic India Limited Biocon House Semicon Park Electronics City Phase 2 Bangalore 560100 Karnataka India Bangalore KARNATAKA 560100 India  Phone     Fax  08028085000   Email  sivakumar.vaidyanathan@biocon.com
Source of Monetary or Material Support	Biocon Biologics India Limited
Primary Sponsor	Name  Biocon Biologics India Limited  Address  Biocon House, Ground Floor, Tower-3, Semicon Park, Electronic City, Phase - II, Hosur Road, Bengaluru, Karnataka – 560100  Type of Sponsor  Pharmaceutical industry-Indian
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	India
Sites of Study Modification(s)	No of Sites = 4   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Dr Anjan Trikha  All India Institute Of Medical Sciences,  Sri Aurobindo Marg, Ansari Nagar, Ansari Nagar East, New Delhi, Delhi 110029 New Delhi   9810977901 anjantrikha@hotmail.com  Dr Suresh Kumar  MAMC medical college and Lok Nayak Jai Prakash Narayan Hospital hospital  MAMC medical college and Lok Nayak Jai Prakash Narayan Hospital hospital, Jawaharlal Nehru Marg, Maulana Azad Medical College Campus, Delhi Gate, New Delhi, Delhi 110002 New Delhi   9891158991 drskumar31@yahoo.co.in  Dr Milind Nadkar  Seth GS Medical College and KEM Hospital   Department of Medicine Seth GS Medical College and KEM Hospital Acharya Donde Marg, Parel, Mumbai, Maharashtra 400012 Mumbai   9820060705 milindnadkar@yahoo.com  Dr Rosemari De Souza  Topiwala National Medical College & B. Y. L. Nair Charitable Hospital,  Dr. A. L. Nair Road, Mumbai - 400008 Mumbai   9820056230 drrosemariedesouza@gmail.com
Details of Ethics Committee Modification(s)	No of Ethics Committees= 4   Name of Committee  Approval Status  EC Seth GS Medical College and KEM Hospital, Mumbai  Approved  IEC Topiwala National Medical College B. Y. L. Nair Charitable Hospital Mumbai 400008  Approved  IEC, MAMC, New Delhi 11002  Approved  Institute Ethics Committee, AIIMS, New Delhi  Approved
Regulatory Clearance Status from DCGI Modification(s)	Status  Approved/Obtained
Health Condition / Problems Studied Modification(s)	Health Type  Condition  Patients  Coronavirus as the cause of diseases classified elsewhere  Patients  Respiratory conditions due to other external agents
Intervention / Comparator Agent Modification(s)	Type  Name  Details  Intervention  Arm A Best supportive care with Itolizumab  Start at 1.6 mg/kg dose iv infusion, if well tolerated and improvement in patient observed, investigator has the discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen.  Comparator Agent  Arm B Best supportive care  By best supportive care” which includes antivirals /antibiotics/ hydroxychloroquine; oxygen therapy, will be administered. The best supportive care will be as per institution standard
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 (not tested in children yet) 2. Informed consent for participation in the study 3. Virological diagnosis of SARS-CoV2 infection (PCR) 4. Hospitalized due to clinical/instrumental diagnosis of COVID-19 infection 5. Oxygen saturation at rest in ambient air ≤94% 6. Patients who are in moderate to severe ARDS as defined by PaO2/Fio2 ratio of < 200 or more than 25% detoriation from the immediate previous value.
ExclusionCriteria	Details  1. Known severe allergic reactions to monoclonal antibodies 2. Active tuberculosis (TB) infection 3. History of inadequately treated tuberculosis or latent tuberculosis 4. In the opinion of the investigator,progression to death is highly probable, irrespective of the provision of treatments 5. Have received oral anti-rejection or immune-suppressive drugs within the past 6 months 6. Participating in other drug clinical trials (participation in COVID-19 anti-viral trials may be permitted if approved by Medical Monitor) 7. Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination 8. Patients with known history of Hepatitis B, Hepatitis C or HIV 9. Absolute Neutrophils count (ANC) <1000 / mm3 10. Platelets <50,000 / mm3 11. Absolute Lymphocyte count (ALC): <500/mm3
Method of Generating Random Sequence Modification(s)	Computer generated randomization
Method of Concealment	Not Applicable
Blinding/Masking	Open Label
Primary Outcome Modification(s)	Outcome  TimePoints  1 one month mortality rate 2 Proportion of pts with deterioration of lung function as measured by • Stable SpO2; PaO2 without increasing FiO2 3 Reduction of endotracheal intubation rate, measured as rate of pts needing intubation 4 Reduction in proportion of pts who need • NIV • IMV • HFNO 5 Time of duration of mechanical ventilation, for pts needing intubation 6 Change in inflammatory markers CRP, d-Dimer, ferritin   up to One-month
Secondary Outcome Modification(s)	Outcome  TimePoints  Biomarkers (IL-6, TNF-a)   up to One-month  Duration of hospitalization  up to One-month  Lymphocyte count  up to One-month  PaO2 / FiO2 ratio   up to One-month  Radiological response  up to One-month   Remission of respiratory symptoms  up to One-month  Treatment-related side effects as assessed by CTCAE   up to One-month
Target Sample Size	Total Sample Size="30" Sample Size from India="30"
Phase of Trial	Phase 2
Date of First Enrollment (India) Modification(s)	01/05/2020
Date of First Enrollment (Global)	No Date Specified
Estimated Duration of Trial	Years="0" Months="3" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Not Applicable
Recruitment Status of Trial (India)	Completed
Publication Details	None Yet
Brief Summary	This is a Multi-Centric, Open label, Two Arm Randomized, Pivotal Phase 2 Study. All eligible patients entering into the study will be randomized in 2:1 ratio to receive the treatment A (Best supportive care + Itolizumab) / B (Best supportive care) respectively. Each patient will undergo the treatment based on their assigned treatment for a month along with battery of tests that includes, but not limited to, cytokines and chemokine, along with daily recording of TLC; DLC, ANC, ALC; Platelet count; S. creatinine; T.Bilirubin; morning Vitals –pulse, BP, RR; Temperature (highest temperature of the day), PaO2/FiO2, MAP, GCS.     As Itolizumab is an investigational drug, the benefit to COVID-19 patients experiencing complications such as Cytokine Release Syndrome is not known. However, findings from this study may be beneficial to the society at a large at the National and International Level.