An Adaptive, Seamless Phase 1, Followed by Phase 2 Randomized, Double-blind, Multicenter Study
to Evaluate the Safety, Reactogenicity, Tolerability and Immunogenicity of the Whole-Virion
Inactivated SARS-CoV-2 Vaccine (BBV152) in Healthy Volunteers
Whole-Virion Inactivated SARS-CoV-2 vaccine (BBV152) with three formulations, BBV152A, BBV152B and BBV152C.
Dose: 0.5ml,
Route of administration:Intramuscular injection,
Frequency: Two doses at Day 0 and Day 14
Comparator Agent
Placebo
Placebo will be used as a control.
Dose: 0.5ml
Route of administration:Intramuscular injection,
Frequency:Two doses at Day 0 and Day 14
Phase 1
1. Ability to provide written informed consent (Audio video consent for vulnerable
subjects).
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.
Phase 2:
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.
ExclusionCriteria
Details
Phase 2:
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/or 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.
Re-Vaccination Exclusion Criteria
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 /or 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.
Re-Vaccination Exclusion Criteria
26. Pregnancy.
27. Anaphylactic reaction following administration of the investigational vaccine.
28. Virologically confirmed cases of COVID-19.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Phase 1:
1. The occurrence of immediate adverse events within two hours of vaccination 2. The occurrence of adverse events within 7 days of vaccination.3. The occurrence of any adverse events throughout the study duration 4. The occurrence of serious adverse events (SAEs)
Phase 2:
Primary
1. To evaluate the immunogenicity in terms of GMT and four-fold seroconversion
rate amongst the two selected BBV152 vaccine formulations
Phase 1:
Occurrence of Adverse events within 2hrs, at Day 7 and through out the study duration
Phase 2:
Day 0, Day 14, Day 28, Day 42 Day 104 and Day 194 in two cohorts
Phase 1
To evaluate the immunogenicity in terms of GMT and four-fold seroconversion rate
of neutralizing antibodies (NAbs) across the three formulations of BBV152 in
comparison with control group.
Phase 2
The occurrence of immediate adverse events within two hours of vaccination.2. The occurrence of adverse events within seven days of vaccination 3. The occurrence of any adverse events throughout the study duration 4. The occurrence of serious adverse events (SAEs).
Phase 1:
Day 0, Day 14, Day 28, Day 42 Day 104 and Day 194 in two cohorts.
Phase 2:
Occurrence of Adverse events within 2hrs, at Day 7 and through out the study duration
Target Sample Size
Total Sample Size="1125" Sample Size from India="1125"
This is a phase 1 to be followed by phase 2 randomized, double-blind, multicenter study to evaluate the safety, reactogenicity, tolerability and immunogenicity of the Whole-Virion Inactivated SARS-CoV-2 vaccine (BBV152) in healthy volunteers.
The study is designed to evaluate the safety, reactogenicity, tolerability, and immunogenicity of three groups of healthy volunteers who receive two intramuscular doses of BBV152 vaccine formulations. A total sample size of 1125 healthy volunteers, with 375 volunteers in the phase 1 study and 750 volunteers in phase 2 study (4:1 test and control).
