FULL DETAILS (Read-only)  -> Click Here to Create PDF for Current Dataset of Trial
CTRI Number  CTRI/2020/11/028976 [Registered on: 09/11/2020] Trial Registered Prospectively
Last Modified On: 05/12/2020
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Vaccine 
Study Design  Other 
Public Title of Study   A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy, Safety, Immunogenicity,and Lot-to-Lot consistency of BBV152, a Whole virion Inactivated Vaccine in Adults greater than or equal to 18 Years of Age. 
Scientific Title of Study   An Event-Driven,Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy, Safety, Immunogenicity,and Lot-to-Lot consistency of BBV152, a Whole virion Inactivated SARS-CoV-2 Vaccine in Adults greater than or equal to 18 Years of Age. 
Trial Acronym  COVID Phase 3 Study 
Secondary IDs if Any  
Secondary ID  Identifier 
BBIL/BBV152-C/2020 Version No: 3.0; Date: 20-10-2020  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Krishna Mohan 
Designation  Whole-time Director 
Affiliation  Bharat Biotech International limited 
Address  Medical Affairs Department, Bharat Biotech International Ltd, Genome valley, Shameerpet

Medchal
TELANGANA
500078
India 
Phone  914023480567  
Fax  914023480560  
Email  kmohan@bharatbiotech.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Krishna Mohan 
Designation  Whole-time Director 
Affiliation  Bharat Biotech International limited 
Address  Medical Affairs Department, Bharat Biotech International Ltd, Genome valley, Shameerpet

Medchal
TELANGANA
500078
India 
Phone  914023480567  
Fax  914023480560  
Email  kmohan@bharatbiotech.com  
 
Details of Contact Person
Public Query
 
Name  Dr Shashikanth Muni 
Designation  Associate Medical Director 
Affiliation  Bharat Biotech International limited 
Address  Medical Affairs Department, Bharat Biotech International Ltd, Genome valley, Shameerpet

Medchal
TELANGANA
500078
India 
Phone  914023480567  
Fax  914023480560  
Email  shashikanth4257@bharatbiotech.com  
 
Source of Monetary or Material Support  
Indian Council of Medical Research (ICMR), New Delhi 
 
Primary Sponsor  
Name  Bharat Biotech International Ltd 
Address  Bharat Biotech International Ltd Genome Valley Shameerpet Hyderabad – 500 078 Telagana INDIA 
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
The Indian Council of Medical Research ICMR New Delhi  Indian Council of Medical Research V. Ramalingaswami Bhawan, P.O. Box No. 4911 Ansari Nagar, New Delhi - 110029, India 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 25  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr E Venkat Rao  Institute of Medical Sciences and SUM Hospital  DEPARTMENT OF COMMUNITY MEDICINE, 3rd Floor, K-8, KALINGA NAGAR, GHATIKIA
Jajapur
ORISSA 
07853889552

e.venkata.rao@gmail.com 
Dr Satyajit Mohapatra   SRM Hospital & Research center  Department of Pharmacology , SRM Medical College Hospital and Research Centre, Kattankulathur Campus
Kancheepuram
TAMIL NADU 
09791161626

satyajitmp@gmail.com 
Dr Anjan Jyoti Talukdar  Gauhati Medical College & Hospital   Department of Medicine, Gauhati Medical College & Hospital Bhangagarh, Kamrup, Assam - 781032
Kamrup
ASSAM 
09954658926

dranjan_t@yahoo.co.in 
Dr N T Awad  Lokamanya tilak Municipal Medical College and General hospital  Department of Respiratory Medicine,Lokamanya tilak Municipal Medical College and General hospital DrAmbedkar road Sion Mumbai 400022
Mumbai
MAHARASHTRA 
9322252708

nta1960@gmail.com 
Dr C Prabhakar Reddy  Nizam’s Institute of Medical Sciences  NIMS Old Block,ward No 11,second floor, near ward no 11 opp NP@ Department of Clinical Pharmacology & Therapeutics, (CP&T),Hyderabad
Hyderabad
TELANGANA 
7416512888

cptnims@gmail.com 
Dr Shiva Narang  Guru Teg bahadur Hospital  Department of Medicine Guru Teg bahadur Hospital Dilshad Garden Delhi 110095
East
DELHI 
9899838807

shivanarang@gmail.com 
Dr Manish Multani  Rahate Surgical Hospital   Near Telephone exchange Square 517 Juni Mangalwari Central Avenue nagpur 440008
Nagpur
MAHARASHTRA 
8983178550

mkmultani@gmail.com 
DrAnil Kumar Pandey  ESIC Medical College and Hospital  ESIC Medical College and Hospital NH-3 behind BK Hospital New Industrial Town, Faridabad Harvana 121012
Faridabad
HARYANA 
7042918222

registraracademicfbd@gmail.com 
Dr Sanjay Kumar Rai  All India Institute of Medical Sciences  Dr. Sanjay K. Rai, Professor, Room No. 29 Department of Centre for Community Medicine All India Institute of Medical Sciences, Ansari Nagar New Delhi India 110029
New Delhi
DELHI 
9868397358

drsanjay.aiims@gmail.com 
Dr Priti Meshram   Grant Government Medical College and Sir J.J. Group of Hospitals  Grant Government Medical College and Sir J.J. Group of Hospitals. J J Marg, Nagpada, Mumbai Central, Mumbai, Maharashtra 400008
Mumbai
MAHARASHTRA 
9323198298

drpritimeshram@gmail.com 
Dr Chadramani Singh   All India Institute of Medical Sciences  Dr. Chandramani Singh, Professor, Room No. 1 Department of Community & Family Medicine All India Institute of Medical Sciences, Aurangabad Road Phulwari Sharif Patna Bihar- 801507
Patna
BIHAR 
7607141970

drcmsingh@aiimspatna.org 
Dr Pajanivel Ranganadin   Mahatma Gandhi Medical College& Research Institute  Mahatma Gandhi Medical College& Research Institute, Pondicherry- Cuddalore, ECRMain Road, Pillayarkuppam 607-402, Pondicherrv, India
Pondicherry
PONDICHERRY 
9443493122

pajanivelr@mgmcri.ac.in 
Dr Akshata  Vydehi Institute of Medical Sciences and Research Centre   Vydehi Institute of Medical Sciences and Research Centre 82, near BMTC 181h Depot, Vijayanagar, Nallurhalli, Whitefield, Bengaluru, Karnataka 560066
Bangalore
KARNATAKA 
9845244541

dr_akshata@yahoo.co.in 
Dr Venugopal  King George Hospital  Assistant professor of Medicine, King George Hospital , Maharani Peta, Visakhapatnam,Andhra Pradesh 530002
Visakhapatnam
ANDHRA PRADESH 
9848027203

fbnc.amc@gmail.com 
Dr Raghavendra Gumashta   Peoples College Of Medical Sciences & Research Centre And Associated People’s Hospital  Peoples College Of Medical Sciences & Research Centre And Associated People’s Hospital, Peoples Campus, Bhanpur, Bhopal, Madhya Pradesh 462037
Bhopal
MADHYA PRADESH 
9425324588

rgumashta@gmail.com 
Dr Simmi Dube  Gandhi Medical College   Gandhi Medical College Sultania Rd, near Hamidia Hospital, Royal Market, Medical College Campus, Kohefiza, Bhopal, Madhya Pradesh 462001
Bhopal
MADHYA PRADESH 
9479554822

simmi33@gmail.com 
Dr Savita Verma  Pt BD Sharma,PGIMS/UHS. Rohtak, Haryana   PGIMS Room no428 Department of Pharmacology Directorate Office of Rohtak Pt BD SHARMA,PGIMS/UHS. Rohtak, HARYANA
Rohtak
HARYANA 
9812283746

verma.savi@gmail.com 
Dr Sagar Vivek Redkar  Redkar Hospital and Research Centre  Redkar Hospital and Research Centre Consultant Physician Room No. 11, Mumbai Goa Highway, Oshalbag Village Dhargal, Tal- Pernem. Goa- 403513, India
North Goa
GOA 
09146885522

drsagarredkar@gmail.com 
Dr Laxmi S Kumari  Guntur Medical College  Department of Pulmonary Medicine, Government Fever Hospital, Government General Hospital, Gorantla, Guntur - 5220020
Guntur
ANDHRA PRADESH 
9440879887

laxmikumarisomishetty@gmail.com 
Dr Parul Bhatt   Gmers Medical College and Civil Hospital  225, Sola Gam Rd, beside High Court, Shenbhai Nagar, Sola, Ahmedabad, Gujarat 380060
Ahmadabad
GUJARAT 
9879599595

parubhatt30@yahoo.com 
Dr Mohammad Shameem  Aligarh Muslim University  Department of Tuberculosis and respiratory diseases, Professor Interventional Pulmonology Aligarh, Uttar Pradesh 202001
Aligarh
UTTAR PRADESH 
9412731835

mshameem@myamu.ac.in 
Dr Suman Kanungo  ICMR-National Institute of Cholera and Enteric Diseases  Deputy Director (Scientist E),P-33, CIT Rd, Subhas Sarobar Park, Phool Bagan, Beleghata, Kolkata, West Bengal 700010
Kolkata
WEST BENGAL 
9903824322

sumankanungo@gmail.com 
DR T S Selvavinayagam  Directorate Of Public Health and Preventive Medicine  DIRECTORATE OF PUBLIC HEALTH AND PREVENTIVE MEDICINE, 359, ANNA SALAI, DMS COMPLEX, TEYNAMPET, CHENNAI -600006
Chennai
TAMIL NADU 
9791736334

drsvinayagam@gmail.com 
Dr Jitendra SIngh Kushwaha  Prakhar Hospital  8/219 Khalasi Line Arya Nagar 3rd floor Kanpur Uttar Prasedh
Kanpur Nagar
UTTAR PRADESH 
08448522450

dr.jskushwahacr@gmail.com 
Dr Anupam Sachdeva  Sir Ganga Ram Hospital  Sir Ganga Ram Hospital (SGRH), New Delhi-110060, INDIA.
New Delhi
DELHI 
9811043476

anupamace@yahoo.co.in 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 25  
Name of Committee  Approval Status 
Ethics Committee Sir Ganga Ram Hospital  Submittted/Under Review 
Institutional Ethical Commitee, Gauhati Madical College and Hospital  Submittted/Under Review 
Institutional Ethics Committe Aligarh Muslim University UP  Approved 
Institutional Ethics Committee SRM College Hospital and Research Centre Tamil Nadu  Approved 
Institutional Ethics Committee All India Institute of Medical Sciences Bihar  Approved 
Institutional Ethics Committee All India Institute of Medical Sciences New Delhi  Approved 
Institutional Ethics Committee Baba Raghav Das Medical College, Gorakhpur, Uttar Pradesh   Submittted/Under Review 
Institutional ethics committee DIRECTORATE OF PUBLIC HEALTH AND PREVENTIVE MEDICINE,Chennai  Approved 
Institutional Ethics Committee Gandhi Medical College Bhopal, Madhva Pradesh  Submittted/Under Review 
Institutional ethics committee Gmers Ahmedabad  Approved 
Institutional Ethics Committee Grant Government Medical College and Sir J.J. Group of Hospitals Maharashtra  Approved 
Institutional ethics committee ICMR-National Institute of Cholera and Enteric Diseases Kolkatta,West Bengal  Approved 
Institutional Ethics Committee King George Hospital Visakhapatnam  Submittted/Under Review 
Institutional Ethics Committee Lokmanya Tilak Municipal Medical College & General Hospital  Approved 
Institutional Ethics Committee Mahatma Gandhi Medical College& Research Institute, Pondicherry  Approved 
Institutional Ethics Committee Peoples university Bhopal, Madhya Pradesh   Approved 
Institutional Ethics Committee Pt BD Sharma,PGIMS/UHS.Rohtak, Harvana   Approved 
Institutional Ethics Committee Rahate Surgical Hospital & ICU Nagpur  Approved 
Institutional Ethics Committee Redkar Hospital and Research Centre Oshalbag Village Dhargal, Tai- Pernem. Goa  Approved 
Institutional Ethics Committee Vydehi Institute of Medical Sciences and Research Centre Bengaluru, Karnataka  Approved 
Institutional Ethics Committee, Guntur Medical College, Government Fever Hospital, Government General Hospital, Gorantla, Guntur  Approved 
Institutional Ethics Committee, IMS & SUM Hospital  Approved 
Institutional Ethics Committee, UCMS & GTB Hospital  Submittted/Under Review 
NIMS Institutional Ethics Committee, Nizams institute of Medical Sciences, Punjagutta,  Approved 
Translational Health Science and Technology Institute(THSTI), ESIC Medical College and Hospital Faridabad  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Healthy Human Volunteers  Active immunization for the prevention of SARS-CoV-2 infection 
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  BBV152B: 6 µg antigen with Algel-IMDG   Whole-Virion Inactivated SARS-CoV-2 vaccine (BBV152) will be administered as a two dose intramuscular injection 28 days apart.  
Comparator Agent  Placebo (Phosphate buffered saline with Algel)  Phosphate buffered saline with Alum (without antigen) will be used as the control.will be administered as a two dose intramuscular injection 28 days apart. 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1. Ability to provide written informed consent and availability to fulfill the study requirements. 2. Participants of either gender of aged 18 years and above. 3. Participants with good general health as determined by the discretion of the investigator, or participants with stable medical conditions. A stable medical condition is defined as a disease not requiring significant change in therapy or hospitalization or worsening disease during the 3 months before enrolment. 4. For a female participant of child-bearing potential, planning to avoid becoming pregnant (use of an effective method of contraception or abstinence) from the time of study enrolment until at least eight weeks after the last vaccination. 5. Male subjects of reproductive potential: Use of condoms to ensure effective contraception with the female partner and to refrain from sperm donation from first vaccination until at least 3 months after the last vaccination. 6. Agrees not to participate in another clinical trial at any time during the study period. 7. Agrees not to take any COVID-19 licensed vaccination for the entire duration of the study. 8. Agrees to remain in the study area for the entire duration of the study. 9. Willing to allow storage and future use of biological samples for future research.  
 
ExclusionCriteria 
Details  1. History of any other COVID-19 investigational or licensed vaccination. 2. Known history of SARS-CoV-2 infection, as declared by the subject. 3. For women, positive urine pregnancy test before the first dose of vaccination, or any time during the study period. 4. Temperature >38.0°C (100.4°F) or symptoms of an acute self-limited illness such as an upper respiratory infection or gastroenteritis within three days prior to each dose of vaccine. 5. Resident of COVID-19 infection in same household.
6. Known case of HIV, hepatitis B, or hepatitis C infection. 7. Receipt of any licensed/experimental vaccine within four weeks before enrolment in this study. 8. Receipt of immunoglobulin or other blood products within the three months before vaccination in this study. 9. Immunosuppression as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months. 10. Immunoglobulins, anti-cytokine antibodies and blood products within 6 months prior to study vaccination, during and 21 days following last dose of vaccination. 11. Pregnancy, lactation, or willingness/intention to become pregnant during the first 6 months after enrolment. 12. Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder,, and neurological illness (mild/moderate well-controlled comorbidities are allowed)
Re-Vaccination Exclusion Criteria 13. Pregnancy. 14. History of virologically (RT-PCR) confirmed SARS-CoV-2 infection 15. Anaphylactic reaction following administration of the investigational vaccine.  
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant, Investigator and Outcome Assessor Blinded 
Primary Outcome  
Outcome  TimePoints 
To evaluate the efficacy of BBV152B to prevent symptomatic COVID-19(Virologically confirmed-(RT-PCR positive) which include any participant who meets the Case Definitions for Symptomatic Endpoint and Severe Symptomatic COVID-19  Day 42 to Month 12 
 
Secondary Outcome  
Outcome  TimePoints 
EFFICACY:To evaluate the efficacy of BBV152B to prevent-
1. COVID-19 based on the case definition for the secondary efficacy symptomatic endpoint.
2.COVID-19-Virologically confirmed (RT-PCR positive) severe cases of COVID19.
3.Any severity of COVID-19 by age.
4.Asymptomatic COVID-19.
5.COVID-19 regardless of symptomatology or severity
6.COVID-19 related deaths
7.Symptomatic COVID-19, regardless of the previous infection 
1.Day 42 to Month 12
2.Day 42 to Month 12.
3.Day 42 to Month 12
4.Month 2 to Month 12
5.Day 42 to Month 12
6.Day 42 to Month 12
7.Day 42 to Month 12 
SAFETY
To assess the safety of BBV152B 1.Serious Adverse Events occurring at any time
2.Solicited local and systemic adverse events (AEs).
3.Unsolicited AEs occurring between the vaccination and 28 days after the final vaccination.
4.Immediate AEs with 30 minutes of vaccination
5. Medically attended adverse events (MAAEs) or AEs leading to withdrawal
6.The occurrence of enhanced respiratory disease episodes reported by participant/documented in hospital records 7.AE of Special interest 
1.Throughout the study period
2.Within 7 days post each vaccination
3.Till 28 days post second dose vaccination
4. Within 30 minutes post each vaccination
5.Throughout the study period
6.Throughout the study period 7.Throughout the study period 
IMMUNOGENECITY
To evaluate the immunogenicity of BBV152B
1.Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb)
2.Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Neutralizing Antibody (nAb).
3.Geometric Mean Titer (GMT) of SARS-CoV-2 S1 protein-specific Binding Antibody (bAb).
4.Lot-to-Lot consistency will be assessed based on the neutralizing titer of the three consistent lots used in the trial 
1.Month 0 to Month 12
2.Month 0 to Month 12
3.Month 0 to Month 12
4.Month 0 to Month 2 
 
Target Sample Size   Total Sample Size="25800"
Sample Size from India="25800" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   11/11/2020 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   NIL 
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 3 Event Driven, randomized, double-blind, placebo controlled ,multicentre study to evaluate the Efficacy, Safety, and Immunogenicity of BBV152B, a Whole-Virion Inactivated SARS-CoV-2 Vaccine in Volunteers aged 18 years and above.

Protocol Version 1.0 to Version 2.0

·         BBV-152B formulation is chosen based on the Phase 1 interim report which shows that the immunogenicity of BBV-152B is higher compared to BBV-152A although the difference was not statistically different.

·         The primary efficacy endpoint is modified to include the participants who meet the case definition for Severe  symptomatic  COVID-19 .

·         A safety endpoint to include the Adverse Events of Special Interest (AESIs) such as anaphylaxis, generalized convulsion, and vaccine associated enhanced respiratory disease (VAERD) is included.

Protocol Version 2.0 to version 3.0

·         The case definition of symptomatic COVID-19 Endpoint  is modified based on the SEC recommendation.

·         Risks from study participation  (Category 1 and Category 2 &3) is Updated for easy understanding for the participant

A total of 25,800 subjects will be enrolled and randomized in a 1:1 ratio to receive BBV152B vaccine and control. All participants will be assessed for efficacy and safety endpoints and provide a NP swab and blood sample before the first dose of IP. The NP swab and blood collected will be subject to RT-PCR and Anti-SARS-CoV-2 IgG antibodies. The results of this will not affect enrollment of the participant. Participants who are found to be positive for either RT-PCR Or Anti-SARS-CoV-2 IgG antibodies will be excluded from the primary efficacy analysis. Safety follow up will be done for all.
In addition, sites will be segregated based on the study objectivies:
Category 1 (Symptomatic): In addition to administering the IP, a series of post-dose telephonic follow-up visits will be scheduled to detect suspect symptomatic COVID-19 infections. If a suspect is identified, a nasopharyngeal sample will be collected from the participant for detecting the presence of COVID-19 infection. Telephonic follow-up will occur at 15 Day intervals. 
Category 2 (Symptomatic/Asymptomatic): In addition to administering the IP, a series of post-dose Nasopharyngeal samples for detecting incidence of asymptomatic COVID-19 infection at 1-Month intervals will be collected
Category 3 (Symptomatic/Asymptomatic+Immunogenicity): In addition to administering the IP and collecting NP samples, a series of blood samples will be collected for analyzing serum for immunological assessments. 
The purpose of this Phase 3 study is to evaluate the protective efficacy, safety, and immunogenicity of the whole-virion inactivated SARS-CoV-2 vaccine, BBV152B. The Phase 3 study will follow randomized study participants for efficacy until virologically confirmed (RT-PCR positive) symptomatic COVID-19 participants will be eligible for the primary efficacy analysis. After reaching the target number (n=130) of symptomatic COVID-19 cases, the study will continue to assess safety until the completion of the study duration.It is planned to continue the Phase 3 trial until 130 study participants in the per-protocol population develop PCR-confirmed symptomatic COVID-19 disease during follow-up beginning 14 days after the second dose of vaccine or placebo. We estimate that approximately 25,800 participants should be randomized to accrue these 130 events.  The Lot-to-Lot consistency (Immunogenicity) study will be nested within the Phase 3 (Efficacy) study (in three selected sites). The Immunogenicity study will assess the immune response of a 2-dose regimen of BBV152B vaccine through geometric mean titers (GMTs) by neutralizing antibody, S-protein, and RBD specific anti-IgG binding titer in a subset of 600 (450 vaccine: 150 control) participants, across three consecutive manufacturing Lots.  Data generated through Day 56 (Month 2) will be unblinded only to the biostatistician for evaluation of immune responses in the Immunogenicity subset.  A Formal interim analyses are planned when approximately 1/3 and 2/3 of the target number of participants with confirmed symptomatic COVID-19 have been accrued, to determine whether the sample size and/or length of follow-up should be increased .This interim report containing safety and immunogenicity data will be submitted to CDSCO. 
 
Close