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.
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.
Secondary IDs if Any
Secondary ID
Registry
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
Address
Medical Affairs Department, Bharat Biotech International Ltd,
Genome valley, Shameerpet
Medchal TELANGANA 500078 India
Phone
914023480567
Fax
914023480560
Email
kmohan@bharatbiotech.com
Details Contact Person Scientific Query
Name
Dr Krishna Mohan
Address
Medical Affairs Department, Bharat Biotech International Ltd,
Genome valley, Shameerpet
Medchal TELANGANA 500078 India
Phone
914023480567
Fax
914023480560
Email
kmohan@bharatbiotech.com
Details Contact Person Public Query
Name
Dr Shashikanth Muni
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
Department of Tuberculosis and respiratory diseases, Professor Interventional Pulmonology Aligarh, Uttar Pradesh 202001 Aligarh
9412731835
mshameem@myamu.ac.in
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
7607141970
drcmsingh@aiimspatna.org
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
9868397358
drsanjay.aiims@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
9791736334
drsvinayagam@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
7042918222
registraracademicfbd@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
9879599595
parubhatt30@yahoo.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
9323198298
drpritimeshram@gmail.com
Dr Laxmi S Kumari
Guntur Medical College
Department of Pulmonary Medicine, Government Fever Hospital, Government General Hospital,
Gorantla, Guntur - 5220020 Guntur
9440879887
laxmikumarisomishetty@gmail.com
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
9903824322
sumankanungo@gmail.com
Dr E Venkat Rao
Institute of Medical Sciences and SUM Hospital
DEPARTMENT OF
COMMUNITY
MEDICINE, 3rd Floor,
K-8, KALINGA NAGAR,
GHATIKIA Jajapur
07853889552
e.venkata.rao@gmail.com
Dr Amit Suresh Bhate
Jeevan Rekha Hospital
1st Floor,
Dr BR Ambedkar Road
Opp civil Hospital Belgaum
9695237796
dr.amitsureshbhate@gmail.com
Dr Vasudev
King George Hospital
Assistant professor of Medicine, King George Hospital , Maharani Peta, Visakhapatnam,Andhra Pradesh 530002 Visakhapatnam
9849153542
vasudev.kgh@gmail.com
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
9322252708
nta1960@gmail.com
Dr Manish Kumar Jain
Maharaja Agrasen Superspecilaity Hospital
Department of Pulmonology
Central Spine
Agrasen Aspatal Marg
Sector-7
Vidyadhar Nagar Jaipur
09414414834
doctormanishjain2@gmail.com
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
9443493122
pajanivelr@mgmcri.ac.in
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
7416512888
cptnims@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
9425324588
rgumashta@gmail.com
Dr VijayKumar Shivajirao patil
Prakash Institute of Medical Science and Technology
Medical Superintendent
2nd floor
Islampur
Sangli Road
Tal-Walwa
Sangli
PGIMS Room no428
Department of Pharmacology
Directorate Office of Rohtak
Pt BD SHARMA,PGIMS/UHS.
Rohtak, HARYANA Rohtak
9812283746
verma.savi@gmail.com
Dr Manish Multani
Rahate Surgical Hospital
Near Telephone exchange Square 517 Juni Mangalwari Central Avenue nagpur 440008 Nagpur
8983178550
mkmultani@gmail.com
Dr Sunita Jaiprakash Ramanand
RCSMGMC & CPR Hospital
Professor and HOD of Pharmacological Department
Dasara Chowk
Town Hall
Bhausingji Road
Kolhapur Kolhapur
8080328480
rcsmgmc.research@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
09146885522
drsagarredkar@gmail.com
Dr Anupam Sachdeva
Sir Ganga Ram Hospital
Sir Ganga Ram Hospital (SGRH),
New Delhi-110060,
INDIA. New Delhi
9811043476
anupamace@yahoo.co.in
Dr Satyajit Mohapatra
SRM Hospital & Research center
Department of
Pharmacology , SRM
Medical College
Hospital and Research
Centre, Kattankulathur
Campus Kancheepuram
09791161626
satyajitmp@gmail.com
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
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
NIMS Institutional Ethics Committee, Nizams institute of Medical Sciences, Punjagutta,
Approved
Prakash Medical college Institutional Ethics Committee
Approved
RCSMGMCIEC
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
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
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
Target Sample Size
Total Sample Size="25800" Sample Size from India="25800"
Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial,Citation DataThe Lancet, ISSN: 0140-6736, Vol: 398, Issue: 10317, Page: 2173-2184
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.
