A Phase 2, Randomized, Double Blind, Multicenter Study to Evaluate the Immunogenicity,Reactogenicity and Safety of an Intranasal Adenoviral vector COVID-19 vaccine (BBV154) in Healthy Volunteers.

A Phase 2, Randomized, Double Blind, Multicenter Study to Evaluate the Immunogenicity, Reactogenicity and Safety of an Intranasal Adenoviral vector COVID-19 vaccine (BBV154) in Healthy Volunteers.

Inclusion

1. Ability to provide written informed consent

2. Participants of either gender of age between ≥18 to ≤60 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; oraltemperature <100.4ºF), medical history, and physical examination).

4. Expressed interest and availability to fulfil 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.

Exclusion

1. History of any other COVID-19 investigational/or licensed vaccination.

2. Unacceptable laboratory abnormality at screening (prior to first

vaccination) or safety testing, as listed below

3. Confirmed SARS-CoV-2 at the time of screening using RT-PCR and

ELISA method.

4. Any history of facial nerve paralysis

5. History of cold, sneezing, nasal obstruction in the past 3 days.

6. Prescribed usage of any nasal spray/or nasal drop medication

7. Any significant abnormality altering the anatomy of the nose in a

substantial way or nasopharynx that may interfere with the aims of the

study and in particular any of the nasal assessments or viral challenge

(historical nasal polyps can be included, but large nasal polyps causing

current and significant symptoms and/or requiring regular treatments in

the last month are excluded)

8. For women of child bearing potential, 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).

9. 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.

10. Medical problems as a result of alcohol or illicit drug use during the

past 12 months.

11. 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.

12. Receipt of any licensed vaccine within four weeks before enrolment in

this study.

13. Known sensitivity to any ingredient of the study vaccines, or a more

severe allergic reaction and history of allergies in the past.

14. Receipt of immunoglobulin or other blood products within the three

months prior to vaccination in this study.

15. 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.

16. 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).

17. Any history of hereditary angioedema or idiopathic angioedema.

18. Any history of anaphylaxis in relation to vaccination.

19. Any history of albumin-intolerance.

20. Pregnancy, lactation, or willingness/intention to become pregnant

during the study.

21. History of any cancer.

22. History of severe psychiatric severe conditions likely to affect

participation in the study.

23. A bleeding disorder (e.g. factor deficiency, coagulopathy or platelet

disorder, or prior history of significant bleeding or bruising following

IM injections or venepuncture.

24. Any other serious chronic illness requiring hospital specialist

supervision.

25. Chronic respiratory diseases like severe acute respiratory syndrome

(SARS), including mild asthma.

26. Chronic cardiovascular disease, gastrointestinal disease, liver disease,

renal disease, endocrine disorder, and neurological illness

27. Morbidly obese (BMI≥35 kg/m2) or underweight (BMI ≤18 kg/m2).

28. Living in the same household of any COVID-19 positive person (at the

time of screening only).

29. 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

30. Pregnancy.

31. Anaphylactic reaction following administration of the investigational

vaccine.

32. Virologically confirmed cases SARS-CoV-2 infection

Objectives

Primary

1. To evaluate the humoral immune

responses of BBV154.

Secondary

2. To evaluate the reactogenicity and

safety of BBV154 (Adenoviral

vectored based SARS-CoV-2

virus) vaccine administered via the

intranasal route.

3. To evaluate the immune responses

against spike protein of SARSCoV-

2 virus and Adenovirus

vector.

Exploratory

*To evaluate the vaccine induced

Cell mediated immune response.

* To evaluate the vaccine secretory

IgA antibody response.

* To evaluate the safety of the

vaccine in terms of assessing

adverse event of special interest

(AESI).

END POINTS

Primary

*GMT of neutralizing antibodies

(NAb’s) by MNT/PRNT assays

across the two groups, from

baseline to days 6+3, 28+2, 42±2,

90±7 and 180±7

Secondary

* The occurrence of immediate

adverse events within 2 hours of

vaccination [Time Frame: within 2

hours post each vaccination]

*The occurrence of solicited

adverse events within seven days

of vaccination [Time Frame: 7

days].

*The occurrence of serious adverse

events (SAEs)

[Time Frame: throughout the study

duration].

*The occurrence of any unsolicited

adverse events up to day 35 from

1st dose vaccination. [Time Frame:

up to day 35 from 1st dose

vaccination].

GMTs of binding antibodies

(bAb’s) IgA and IgG against spike

protein across the two groups,

from baseline to days 28+2, 42±2,

90±7 and 180±7.

*Immune response (binding/ or

neutralization) to the vector will be

assessed by ELISA from baseline

to days 28+2, 42±2, 90±7 and

180±7.

Exploratory

*Vaccine induced cell mediated

immunogenicity and antigen

specific T-cell responses and

cytokines across the two groups,

from baseline to days 6+3, 28+2,

42±2, 90±7 and 180±7.

*GMTs of binding antibodies

(bAb’s) and neutralizing antibody

titers.

* The occurrence of adverse

event of special interest (AESI).

[Time Frame: throughout the study

duration].

STUDY DESIGN

A Phase 2, Randomized, Double Blind, Multicenter Study to Evaluate the

Immunogenicity, Reactogenicity and Safety of an Intranasal Adenoviral vector

COVID-19 vaccine (BBV154) in Healthy Volunteers.

The study is designed to evaluate the safety, reactogenicity, and

immunogenicity of four groups of healthy volunteers who receive either

intranasal vaccine in the form of drops on day 0 and day 28 (Group 1) or

placebo via intranasal route with either dropper (Group 2). A total of 200

subjects will be enrolled in 4:1 ratio and will be conducted in a double blinded

manner.

Group 1 (BBV154-Dropper): In this group, 160 participants will be recruited

and administered with 0.5 mL of vaccine (BBV154) on day 0 and day 28 via

intranasal route with a dropper.

Group 2 (Placebo with Dropper): In this group, 40 participants will be

recruited and administered with placebo on both day 0 and day 28 via

intranasal route with validated dropper.

An interim analysis will be performed at day 42 for Immunogenicity, Safety

and submitted to CDSCO.