Whole-Virion Inactivated SARS-CoV-2 Vaccine (BBV152) for COVID-19 in Healthy Volunteers

NCT ID: NCT04471519

Last Updated: 2022-08-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

755 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-15

Study Completion Date

2021-06-30

Brief Summary

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Double blind, Multi-Centre study to evaluate the safety, reactogenicity, tolerability, and immunogenicity of three investigational vaccine groups and one placebo group in healthy volunteers who receive two intramuscular doses of BBV152 vaccine formulations and placebo. A total sample size of 755 healthy volunteers, with 375 and 380 volunteers in phase 1 and 2 studies, respectively.

A protocol amendment was made to evaluate a boosting regimen at the 6-month interval in the Phase 2 trial. At 6 months post-dose 2, participants who received the 6ug Algel-IMDG allocation were randomized equally to receive a third dose of BBV152 (6ug Algel-IMDG) or placebo.

Detailed Description

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Phase 1 study

The study is designed to evaluate the safety, reactogenicity, tolerability, and immunogenicity of Four arms of healthy volunteers who receive two intramuscular doses of BBV152 vaccine formulations or Placebo. A total no of 375 subjects will be enrolled in 4:1 ratio.

This study will be conducted in a dose escalatory manner with a two-dose regimen fourteen days apart.

Phase 2 study

The study is designed to evaluate the safety, reactogenicity, tolerability, and immunogenicity of two arms of healthy volunteers who will receive two intramuscular doses of BBV152 vaccine formulations (BBV152-A \& BBV152-B) in a 1:1 ratio with dosage schedule on Day 0 and Day 28.

A protocol amendment was made to evaluate a boosting regimen at the 6-month interval in the Phase 2 trial. At 6 months post-dose 2, participants who received the 6ug Algel-IMDG allocation were randomized equally to receive a third dose of BBV152 (6ug Algel-IMDG) or placebo. The investigator, participant and Sponsor were blinded to the allocation.

Conditions

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COVID-19 SARS-CoV-2 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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BBV152A - Phase I

0.5 mL of Whole Virion Inactivated SARS-CoV-2 Vaccine \[BBV152A\], is a liquid vaccine administered intramuscularly twice at Day 0 and Day 14

Group Type EXPERIMENTAL

BBV152A - Phase I

Intervention Type BIOLOGICAL

0.5 ml of the vaccine will be administered intramuscularly twice at Day 0 and Day 14

BBV152B - Phase I

0.5 mL of Whole Virion Inactivated SARS-CoV-2 Vaccine \[BBV152B\], is a liquid vaccine administered intramuscularly twice at Day 0 and Day 14

Group Type EXPERIMENTAL

BBV152B - Phase I

Intervention Type BIOLOGICAL

0.5 ml of the vaccine will be administered intramuscularly twice at Day 0 and Day 14

BBV152C - Phase I

0.5 mL of Whole Virion Inactivated SARS-CoV-2 Vaccine \[BBV152C\], is a liquid vaccine administered intramuscularly twice at Day 0 and Day 14

Group Type EXPERIMENTAL

BBV152C - Phase I

Intervention Type BIOLOGICAL

0.5 ml of the vaccine will be administered intramuscularly twice at Day 0 and Day 14

Placebo - Phase I

0.5 mL of Placebo will be administered intramuscularly twice at Day 0 and Day 14.

Group Type ACTIVE_COMPARATOR

Placebo - Phase I

Intervention Type BIOLOGICAL

0.5 ml of the Placebo will be administered intramuscularly twice at Day 0 and Day 14

BBV152A - Phase II

0.5 mL of Whole Virion Inactivated SARS-CoV-2 Vaccine \[BBV152A\], is a liquid vaccine administered intramuscularly twice at Day 0 and Day 28.

Group Type EXPERIMENTAL

BBV152A - Phase II

Intervention Type BIOLOGICAL

0.5 ml of the vaccine will be administered intramuscularly twice at Day 0 and Day 28

BBV152B - Phase II

0.5 mL of Whole Virion Inactivated SARS-CoV-2 Vaccine \[BBV152B\], is a liquid vaccine administered intramuscularly twice at Day 0 and Day 28

Group Type EXPERIMENTAL

BBV152B - Phase II

Intervention Type BIOLOGICAL

0.5 ml of the vaccine will be administered intramuscularly twice at Day 0 and Day 28

Interventions

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BBV152A - Phase I

0.5 ml of the vaccine will be administered intramuscularly twice at Day 0 and Day 14

Intervention Type BIOLOGICAL

BBV152B - Phase I

0.5 ml of the vaccine will be administered intramuscularly twice at Day 0 and Day 14

Intervention Type BIOLOGICAL

BBV152C - Phase I

0.5 ml of the vaccine will be administered intramuscularly twice at Day 0 and Day 14

Intervention Type BIOLOGICAL

Placebo - Phase I

0.5 ml of the Placebo will be administered intramuscularly twice at Day 0 and Day 14

Intervention Type BIOLOGICAL

BBV152A - Phase II

0.5 ml of the vaccine will be administered intramuscularly twice at Day 0 and Day 28

Intervention Type BIOLOGICAL

BBV152B - Phase II

0.5 ml of the vaccine will be administered intramuscularly twice at Day 0 and Day 28

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Ability to provide written informed consent.
2. Participants of either gender of age between ≥18 to ≤55 years.
3. Good general health as determined by the discretion of investigator (vital signs (heart rate ≥60 to≤100 bpm; blood pressure systolic ≥90 mm Hg and \<140 mm Hg; diastolic ≥ 60 mm Hg and \<90 mm Hg; oral temperature \<100.4ºF), medical history, and physical examination).
4. Expressed interest and availability to fulfill the study requirements.
5. 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 four weeks after the last vaccination
6. Male subjects of reproductive potential: Use of condoms to ensure effective contraception with the female partner from first vaccination until 3 months after last vaccination
7. Male subjects agree to refrain from sperm donation from the time of first vaccination until 3 months after last vaccination
8. Participants must refrain from blood or plasma donation from the time of first vaccination until 3 months after last vaccination
9. Agrees not to participate in another clinical trial at any time during the study period.
10. Agrees to remain in the study area for the entire duration of the study.
11. Willing to allow storage and future use of biological samples for future research.


1. Ability to provide written informed consent (Audio video consent for vulnerable subjects).
2. Participants of either gender of age between ≥12 to ≤ 65 years.
3. Good general health as determined by the discretion of investigator (vital signs (heart rate ≥60 to≤100 bpm; blood pressure systolic ≥90 mm Hg and \<140 mm Hg; diastolic ≥ 60 mm Hg and \<90 mm Hg; oral temperature \<100.4ºF), medical history, and physical examination).
4. Expressed interest and availability to fulfill the study requirements.
5. For a female participant of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) from the time of study enrolment until at least four weeks after the last vaccination and agrees not to participate in another clinical trial at any time during the study period.
6. Male subjects of reproductive potential: Use of condoms to ensure effective contraception with the female partner from first vaccination until 3 months after last vaccination
7. Male subjects agree to refrain from sperm donation from the time of first vaccination until 3 months after last vaccination
8. Participants must refrain from blood or plasma donation from the time of first vaccination until 3 months after last vaccination.
9. Agrees to remain in the study area for the entire duration of the study.
10. Willing to allow storage and future use of biological samples for future research.

Exclusion Criteria

1. History of any other COVID-19 investigational vaccination.
2. Unacceptable laboratory abnormality from screening (prior to first vaccination) or safety testing, as listed below \[Abnormal Complete Blood Count (CBC), Random blood sugar level, Renal function test (serum urea and Creatinine), liver function tests, urine analysis report, Positive serology for hepatitis C or HIV antibody or hepatitis B surface antigen\].

(Subjects will be informed if their results are positive for hepatitis C, HIV 1 \& 2 antibody or hepatitis B surface antigen (HBsAg) and will be referred to a primary care provider for follow up of these abnormal laboratory tests.)
3. Confirmed SARS-CoV-2 at the time of screening using RT-PCR and ELISA method.
4. Health care workers.
5. For women, a positive serum pregnancy test (during screening within 45 days of enrolment) or positive urine pregnancy test (within 24 hours of administering each dose of vaccine).
6. 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.
7. Medical problems as a result of alcohol or illicit drug use during the past 12 months.
8. Receipt of an experimental agent (vaccine, drug, device, etc.) within 60 days before enrollment or expects to receive an investigational agent during the study period.
9. Receipt of any licensed vaccine within four weeks before enrolment in this study.
10. Known sensitivity to any ingredient of the study vaccines, or a more severe allergic reaction and history of allergies in the past.
11. Receipt of immunoglobulin or other blood products within the three months prior to vaccination in this study.
12. 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.
13. Long-term use (\> 2 weeks) of oral or parenteral steroids (glucocorticoids) or high-dose inhaled steroids (\>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding six months (nasal and topical steroids are allowed).
14. Any history of hereditary angioedema or idiopathic angioedema.
15. Any history of anaphylaxis in relation to vaccination.
16. Any history of albumin-intolerance.
17. Pregnancy, lactation, or willingness/intention to become pregnant during the study.
18. History of any cancer.
19. History of psychiatric severe conditions likely to affect participation in the study.
20. A bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder, or prior history of significant bleeding or bruising following IM injections or venepuncture.
21. Any other serious chronic illness requiring hospital specialist supervision.
22. Chronic respiratory diseases like severe acute respiratory syndrome (SARS), including mild asthma.
23. Chronic cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, and neurological illness
24. Morbidly obese (BMI≥35 kg/m2) or underweight (BMI ≤18 kg/m2).
25. Living in the same household of any COVID-19 positive person.
26. Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.

27. Pregnancy.
28. Anaphylactic reaction following administration of the investigational vaccine.
29. Virologically confirmed cases of COVID-19

Phase 2:


1. History of any other COVID-19 investigational vaccination.
2. Confirmed SARS-CoV-2 at the time of screening using RT-PCR and ELISA method.
3. Health care workers.
4. Positive urine pregnancy test (within 24 hours of administering each dose of vaccine).
5. 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.
6. Medical problems as a result of alcohol or illicit drug use during the past 12 months.
7. Receipt of an experimental agent (vaccine, drug, device, etc.) within 60 days before enrolment or expects to receive an investigational agent during the study period.
8. Receipt of any licensed vaccine within four weeks before enrolment in this study.
9. Known sensitivity to any ingredient of the study vaccines, or a more severe allergic reaction and history of allergies in the past.
10. Receipt of immunoglobulin or other blood products within the three months prior to vaccination in this study.
11. 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.
12. Long-term use (\> 2 weeks) of oral or parenteral steroids (glucocorticoids) or high-dose inhaled steroids (\>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding six months (nasal and topical steroids are allowed).
13. Any history of hereditary angioedema or idiopathic angioedema.
14. Any history of anaphylaxis in relation to vaccination.
15. Any history of albumin-intolerance.
16. Pregnancy, lactation, or willingness/intention to become pregnant during the study.
17. History of any cancer.
18. History of psychiatric severe conditions likely to affect participation in the study.
19. A bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder, or prior history of significant bleeding or bruising following IM injections or venepuncture.
20. Any other serious chronic illness requiring hospital specialist supervision.
21. Chronic respiratory diseases like severe acute respiratory syndrome (SARS), including mild asthma.
22. Chronic cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, and neurological illness
23. Morbidly obese (BMI≥35 kg/m2) or underweight (BMI ≤18 kg/m2).
24. Living in the same household of any COVID-19 positive person.
25. Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.

26. Pregnancy.
27. Anaphylactic reaction following administration of the investigational vaccine.
28. Virologically confirmed cases of COVID-19.
Minimum Eligible Age

12 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Indian Council of Medical Research

OTHER_GOV

Sponsor Role collaborator

Bharat Biotech International Limited

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dr. Savita Verma, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

PGIMS, Rohtak

Dr. Sanjay Kumar Rai, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

All India Institute of Medical Sciences, Delhi

Dr. Chandramani Singh, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

All India Institute of Medical Sciences

Dr. Ajeeth Pratap Singh, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

Rana Hospital and Trauma Centre, Gorakhpur

Dr. Satyajit Mohapatra, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

SRM Hospital and Research Centre, Chennai

Dr. Prabhakar Reddy, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

Nizams Institute of Medical Sciences, Hyderabad

Dr. Venkata Rao, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

IMS & SUM Hospital, Orissa

Dr. Jitendra Kushwaha, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

Prakhar Hospital, Kanpur

Dr. Sagar Vivek Redkar, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

Redkar Hospital and Research Center, Goa

Dr. Amit Bhate, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

Jeevan Rekha Hospital, Belguam

Dr. Chadrashekar Gillukar, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

Gillukar Multispeciality Hospital, Nagpur

Dr Vasudev R, MBBS, MD

Role: PRINCIPAL_INVESTIGATOR

King George Hospital

Locations

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King George Hospital

Visakhapatnam, Andhra Pradesh, India

Site Status

All India Institute of Medical Sciences

Patna, Bihar, India

Site Status

Pt BD SHARMA,PGIMS/UHS

Rohtak, Haryana, India

Site Status

Jeevan Rekha Hospital

Belagavi, Karnataka, India

Site Status

Gillukar Multispeciality Hospital

Nagpur, Maharashtra, India

Site Status

All India Institute of Medical Sciences

Delhi, New Delhi, India

Site Status

Institute of Medical Sciences and SUM Hospital

Bhubaneswar, Odisha, India

Site Status

SRM Hospital & Research center

Chennai, Tamil Nadu, India

Site Status

Nizam's Institute of Medical Sciences

Hyderabad, Telangana, India

Site Status

Rana Hospital and Trauma Center

Gorakhpur, Uttar Pradesh, India

Site Status

Prakhar Hospital

Kanpur, Uttar Pradesh, India

Site Status

Redkar Hospital and Research Centre

Goa, , India

Site Status

Countries

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India

References

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Vadrevu KM, Ganneru B, Reddy S, Jogdand H, Raju D, Sapkal G, Yadav P, Reddy P, Verma S, Singh C, Redkar SV, Gillurkar CS, Kushwaha JS, Mohapatra S, Bhate A, Rai SK, Ella R, Abraham P, Prasad S, Ella K. Persistence of immunity and impact of third dose of inactivated COVID-19 vaccine against emerging variants. Sci Rep. 2022 Jul 14;12(1):12038. doi: 10.1038/s41598-022-16097-3.

Reference Type DERIVED
PMID: 35835822 (View on PubMed)

Ella R, Reddy S, Jogdand H, Sarangi V, Ganneru B, Prasad S, Das D, Raju D, Praturi U, Sapkal G, Yadav P, Reddy P, Verma S, Singh C, Redkar SV, Gillurkar CS, Kushwaha JS, Mohapatra S, Bhate A, Rai S, Panda S, Abraham P, Gupta N, Ella K, Bhargava B, Vadrevu KM. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: interim results from a double-blind, randomised, multicentre, phase 2 trial, and 3-month follow-up of a double-blind, randomised phase 1 trial. Lancet Infect Dis. 2021 Jul;21(7):950-961. doi: 10.1016/S1473-3099(21)00070-0. Epub 2021 Mar 8.

Reference Type DERIVED
PMID: 33705727 (View on PubMed)

Yadav PD, Ella R, Kumar S, Patil DR, Mohandas S, Shete AM, Vadrevu KM, Bhati G, Sapkal G, Kaushal H, Patil S, Jain R, Deshpande G, Gupta N, Agarwal K, Gokhale M, Mathapati B, Metkari S, Mote C, Nyayanit D, Patil DY, Sai Prasad BS, Suryawanshi A, Kadam M, Kumar A, Daigude S, Gopale S, Majumdar T, Mali D, Sarkale P, Baradkar S, Gawande P, Joshi Y, Fulari S, Dighe H, Sharma S, Gunjikar R, Kumar A, Kalele K, Srinivas VK, Gangakhedkar RR, Ella KM, Abraham P, Panda S, Bhargava B. Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques. Nat Commun. 2021 Mar 2;12(1):1386. doi: 10.1038/s41467-021-21639-w.

Reference Type DERIVED
PMID: 33654090 (View on PubMed)

Ella R, Vadrevu KM, Jogdand H, Prasad S, Reddy S, Sarangi V, Ganneru B, Sapkal G, Yadav P, Abraham P, Panda S, Gupta N, Reddy P, Verma S, Kumar Rai S, Singh C, Redkar SV, Gillurkar CS, Kushwaha JS, Mohapatra S, Rao V, Guleria R, Ella K, Bhargava B. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial. Lancet Infect Dis. 2021 May;21(5):637-646. doi: 10.1016/S1473-3099(20)30942-7. Epub 2021 Jan 21.

Reference Type DERIVED
PMID: 33485468 (View on PubMed)

Other Identifiers

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Protocol No:BBIL/BBV152-A/2020

Identifier Type: OTHER

Identifier Source: secondary_id

BBIL/BBV152-A/2020

Identifier Type: -

Identifier Source: org_study_id

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