COVID-19 Respiratory InfectionPhase 3Nasal154PH3NCT05522335
Phase III Study of BBV154 Intranasal Vaccine in Healthy Volunteers
A Phase 3 study testing BBV154(Intranasal) & covaxin in people with COVID-19 Respiratory Infection, run by Bharat Biotech International Limited at 14 sites in India.
Trial summary
Group 1 (BBV154): In this group, 3000 participants will be recruited, randomized in 1:1:1 ratio receive 3 consecutive lots (Lot 1: 1000, Lot 2: 1000, Lot 3: 1000) of the BBV154 vaccine (0.5 mL each dose) on day 0 and day 28 via intranasal route. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- COVID-19 Respiratory Infection
- What is being tested?
- BBV154(Intranasal) & covaxin
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,160 participants
- Where
- 14 sitesIndia
- Study dates
- 16 Apr 2022to 28 Feb 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Ability to provide written informed consent.
- Participants of either gender of age ≥18 years.
- 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).
- Expressed interest and availability to fulfill the study requirements.
- 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
- 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
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- Participants must refrain from blood/plasma or any other bodily fluid donation from the time of first vaccination until 3 months after last vaccination
- Agrees not to participate in another clinical trial at any time during the study period.
- Agrees to remain in the study area for the entire duration of the study.
- Willing to allow storage and future use of biological samples (serum) for future research.
- -
Who cannot join
- History of any other COVID-19 investigational/or licensed vaccination.
- 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).
- Temperature >38.0°C (100.4°F) or symptoms of an acute self limiting illness such as an upper respiratory infection or gastroenteritis within three days prior to each dose of vaccine.
- Medical problems because of alcohol or illicit drug use during the past 12 months.
- 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.
- Receipt of any licensed vaccine (other than Covid-19 vaccine) within four weeks before enrolment in this study.
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- Known sensitivity to any ingredient of the study vaccines, or a more severe allergic reaction and history of allergies in the past.
- Receipt of immunoglobulin or other blood products within the three months prior to vaccination in this study.
- Immunosuppressant 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.
- 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 (Topical steroids are allowed).
- Any history of anaphylaxis in relation to vaccination.
- History of any cancer.
- History of severe psychiatric conditions likely to affect participation in the study.
- A bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder, or prior history of significant bleeding or bruising following IM injections or venepuncture).
- Any other serious chronic illness requiring immediate hospital specialist supervision.
- 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. -
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
India14 sites
Aatman Hospital, Ahmedabad
Ahmedabad, Gujarat, 380058
Jeevan Rekha Hospital, Belgaum
Belagavi, Karnataka, 590002
Redkar Hospital and Research center
Dargalim, Goa, 403513
Rana Hospital
Gorakhpur, Uttar Pradesh, 273001
Malla Reddy Narayana Multi Speciality Hospital
Hyderabad, Telangana, 500015
NIMS (Nizam's Institute of Medical Sciences
Hyderabad, Telangana, 500082
Maharaja Agrasen super specality Hospital, Jaipur
Jaipur, Rajasthan, 302039
Rajarajeshwari Medical College and Hospital
Kambīpura, Karnataka, 560074
Prakhar Hospital
Kanpur, Uttar Pradesh, 208002
AIIMS (All India Institute of Medical Sciences)
Patna, Bihar, 801507
Oyster and Pearl Hospitals (Phadnis Clinic Pvt Ltd)
Pune, Maharashtra, 411005
PGIMS (Pt. BD Sharma Postgraduate Institute of Medical Sciences)
Rohtak, Haryana, 124001
VIMS (Visakha Institute of Medical Sciences)
Vizag, Andhrapradesh, 530040
Acharya Vinobha Bhave Rural Hospital
Wardha, Maharashtra, 442004
About this study
Official title: A Phase III Randomized Open Label Multi-center Study to Compare Immunogenicity and Safety of BBV154 With COVAXIN®, and to Assess Lot to Lot Consistency of BBV154 in Healthy Volunteers
Group 1 (BBV154): In this group, 3000 participants will be recruited, randomized in 1:1:1 ratio receive 3 consecutive lots (Lot 1: 1000, Lot 2: 1000, Lot 3: 1000) of the BBV154 vaccine (0.5 mL each dose) on day 0 and day 28 via intranasal route. Group 2 (COVAXIN®): In this group, 160 participants will be recruited and administered with COVAXIN® vaccine on day 0 and on day 28 via intramuscular route.
A total sample size of 3160 healthy volunteer's age's ≥18 years will be recruited in this study. BBV154-Subjects- Part 1 ( Immunogenicity Group)- First 640 Subjects BBV154-Subjects- Part 2 ( Safety Group)- (Remaining 2520 subjects) Visit 1: Baseline (Day 0) Visit 2 (Day 28+2) Visit 3 (Day 42 ± 7 days) Visit 4 (Day 90 ± 7 days) and Visit 5 (Day 180± 7 days)
Read the detailed description
Sample Collection:
- Pregnancy test will be conducted by using rapid test kit.
- Immunogenicity analysis: A total of 5 ml of blood is collected on Day 0, Day 28+2, Day 42±7, Day 90±7 and Day 180±7 (Subset of 640, 160 from each lot and control group). Sera will collect from the blood sample and stored as 3 aliquots at -20°C.
- A saliva sample (5 mL) and an additional blood sample (10mL) will be collected on Day 0, Day 28+2, Day 42±7, Day 90±7 and Day 180±7 (Subset of 80, 60 from Group 1(20 from each lot) and 20 from Group 2).
- Saliva will be collected by Passive droll method using Falcon tube.
Sample Size:
A total sample size of 3160 healthy volunteer's age's ≥18 years will be recruited in this study.
Randomization:
A total of 3000 participants will be randomized in to BBV154 two-dose study arm and 160 participants in the COVAXIN® two-dose arm. The first 640 participants are randomized with block size 4, in 1:1:1:1 ratio [(3 (BBV154): 1 (COVAXIN®)].
Remaining 2520 participants in the study are randomized with the block size 6 in 1:1:1 ratio (BBV154).
STUDY RATIONALE:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is accelerating globally, leading to an increase in morbidity and mortality. The high-risk group includes the health care workers (HCW) (physicians and paramedical staff), working amid SARS-CoV-2 infected patients, all other people including household contacts of COVID-19 confirmed patients, people currently residing or working in COVID-19 hot-spots/outbreak areas where there is a high risk of transmission of SARS-CoV-2 infection and especially the elderly people (age >60 Years). Though SARS-CoV-2 infection may cause mild symptoms in many, nearly 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit (ICU). In severe cases, COVID-19 can be complicated by acute respiratory distress syndrome, sepsis, septic shock, and multi organ failure (2,3).
Though the antiviral drugs such as Remdesivir has been approved for COVID-19 treatment by USFDA, but it fails to prevent COVID-19 deaths (3). Hence, there is a necessity to develop a vaccine to prevent SARS-CoV-2 infection. Various types of COVID-19 vaccines, such as DNA, RNA based formulations, recombinant subunit vaccines containing the viral protein (Spike) epitopes, vector-based mutations (eg: Adenovirus and traditional inactivated vaccines are under development(6-9). A chimpanzee adenoviral vaccine (Adenoviral vectored-SARS-CoV-2-S), encoding prefusion stabilized spike protein of SARS-CoV-2 virus was developed by Washington University School of Medicine, and evaluated the protective activity of the vaccine in challenge studies with SARS-CoV-2 virus and mice expressing human angiotensin-converting enzyme 2 (ACE2) receptor(10). Challenge study results were revealed that intramuscular dosing of Adenoviral vectored-SARS-CoV-2-S vaccine induces systemic humoral and cell mediated immunity and protects against lung infection whereas intranasal dosing of the same vaccine induces both systemic and mucosal immunoglobulins (IgG and IgA) ad protects from lower and upper respiratory tract infections (10). Bharat Biotech has collaborated with Washington University to manufacture the vaccine and conduct clinical trials.
BBV154 intranasal vaccine was evaluated for its safety and immunogenicity in a Phase 1 clinical study in 175 healthy participants and found to be safe and immunogenic with two dose regimen administered with 4 weeks interval. In a Phase 2/3 clinical study, BBV154 vaccine with two dose regimen is further evaluating in 152 participants for its safety and immunogenicity. Bharat Biotech has designed this pivotal Phase 3 study to immunogenicity, safety and lot- to-lot consistency of the BBV154 vaccine compared to COVAXIN® vaccine.
STUDY DESIGN:
The Phase-III study is designed to evaluate the immunogenicity, safety and lot-to-lot consistency of two groups of healthy volunteers who receive either BBV154 vaccine via intranasal route or COVAXIN® vaccine via intramuscular route. A total of 3160 participants will be enrolled and assess for the safety, immunogenicity and lot consistency.
Group 1 (BBV154): In this group, 3000 participants will be recruited, randomized in 1:1:1 ratio receive 3 consecutive lots (Lot 1: 1000, Lot 2: 1000, Lot 3: 1000) of the BBV154 vaccine (0.5 mL each dose) on day 0 and day 28 via intranasal route.
Group 2 (COVAXIN®): In this group, 160 participants will be recruited and administered with COVAXIN® vaccine on day 0 and on day 28 via intramuscular route.
STUDY PROCEDURES
Visit 1: Baseline (Day 0):
- The participant will be screened for eligibility based on medical history, vitals, and physical examination and urine pregnancy test for female participants.
- If the participant is eligible (in good general health or stable pre-existing disease as per the discretion of the Principal investigator), a blood sample will be withdrawn prior to vaccination (Subset).
- Blood sample (5 mL) will be collected from subset (n=640, 160 from each lot of Group 1 \& Group 2) of participants.
- Saliva sample (5 mL) will be collected from subset (n=80, 60 from Group 1 (20 from each lot) and 20 from Group 2) of participants.
- An additional 10 mL of blood sample will be collected from subset (n=80, 60 from Group 1 (20 from each lot) and 20 from Group 2) of participants.
- An intranasal vaccine or COVAXIN® will be administered. Following vaccination, participants will remain at the study site for at least 30 minutes of observation to record any immediate adverse event.
- Diary card will be distributed to the participants.
- Telephonic follow-up (7-days post-vaccination) for adverse event recording. Visit 2 (Day 28+2):
- Study participants will return to the OPD for vitals and physical examination (general and systemic examination and urine pregnancy test for female participants), and specific symptoms for COVID-19.
- Blood sample (5 mL) will be collected from subset (n=640, 160 from each lot of Group 1 \& Group 2) of participants.
- Saliva sample (5 mL) will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- An additional 10 mL of blood sample will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- An intranasal vaccine or COVAXIN® will be administered. Following vaccination, participants will remain at the study site for at least 30 minutes of observation to record any adverse event.
- Diary card will be collected and a new diary card distributed to the participants.
- Telephonic follow-up (7-days post-vaccination) for adverse event recording.
Visit 3 (Day 42 ± 7 days):
- Study participants will return to the OPD for physical examination (general and systemic examination and urine pregnancy test for female participants), and specific symptoms for COVID-19.
- Blood sample (5 mL) will be collected from subset (n=640, 160 from each lot of Group 1 \& Group 2) of participants.
- Saliva sample (5 mL) will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- An additional 10 mL of blood sample will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- Diary card will be collected from the participants.
Visit 4 (Day 90 ± 7 days):
- Study participants (Subset) will return to the OPD for physical examination (general and systemic examination), and specific symptoms for COVID-19.
- Urine pregnancy test for female participants (Immunogenicity subset)
- Blood sample (5 mL) will be collected from subset (n=640, 160 from each lot of Group 1 \& Group 2) of participants.
- Saliva sample (5 mL) will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- An additional 10 mL of blood sample will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- Safety data will be collected from all the participants through telephonically other than immunogenicity subset (Day 90 ± 7 days).
Visit 5 (Day 180± 7 days):
- Study participants (Subset) will return to the OPD for physical examination (general and systemic examination), and specific symptoms for COVID-19.
- Urine pregnancy test for female participants (Immunogenicity subset)
- Blood sample (5 mL) will be collected from subset (n=640, 160 from each lot of Group 1 \& Group 2) of participants.
- Saliva sample (5 mL) will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- An additional 10 mL of blood sample will be collected from subset (n=80, 60 from Group 1 (20 from each lot) and 20 from Group 2) of participants.
- Safety data will be collected from all the participants through telephonically other than immunogenicity subset (Day 180 ± 7 days).
Safety Monitoring:
Subjects will be observed for 30 minutes after vaccination for immediate adverse events. Active surveillance will be conducted for all participants for seven days after each dose of vaccine to ascertain information on solicited adverse events ("Reactogenicity"). Safety data will be collected from all the participants through telephonically on Day 90± 7 and 180± 7.
- Conditions
- COVID-19 Respiratory Infection
- Being tested
- BBV154(Intranasal) & covaxin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BBV154(Intranasal) & covaxinBiological
Intervention Covaxin
| Study group | Role | What they receive |
|---|---|---|
| BBV154 Lot-1 | Active comparator | Safety Group : In this group, 1000 participants will be recruited, receive BBV154 vaccine (0.5 mL each dose) on day 0 and day 28 via intranasal route and assess for the safety. Receives: Biological: BBV154(Intranasal) & covaxin |
| BBV154 Lot-2 | Active comparator | Safety Group : In this group, 1000 participants will be recruited, receive BBV154 vaccine (0.5 mL each dose) on day 0 and day 28 via intranasal route and assess for the safety. Receives: Biological: BBV154(Intranasal) & covaxin |
| BBV154 Lot-3 | Active comparator | Safety Group : In this group, 1000 participants will be recruited, receive BBV154 vaccine (0.5 mL each dose) on day 0 and day 28 via intranasal route and assess for the safety. Receives: Biological: BBV154(Intranasal) & covaxin |
| COVAXIN® | Active comparator | Immunogenicity Group :In this group, 160 participants will be recruited, receive Covaxin vaccine (0.5 mL each dose) on day 0 and day 28 via intramuscular route and assess for the Immunogenicity. Receives: Biological: BBV154(Intranasal) & covaxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric mean titres (GMTs
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays.
Measured: baseline
Geometric mean titres (GMTs
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays.
Measured: Day 28+2
Geometric mean titres (GMTs)
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays
Measured: Day 42±7
Geometric mean titres (GMTs)
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays
Measured: Day 90±7
Geometric mean titres (GMTs)
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays
Measured: Day 180±7.
solicited adverse events
The occurrence of solicited adverse events within seven days of vaccination
Measured: 7days
unsolicited adverse events
The occurrence of any unsolicited adverse events up to day 180 from 1st dose vaccination.
Measured: day 180
Secondary outcomes (10)
Geometric mean titers (GMTs)
salivary IgA (n=80), Serum IgA and IgG binding antibody titer by ELISA assays
Measured: baseline
Geometric mean titers (GMTs)
salivary IgA (n=80), Serum IgA and IgG binding antibody titer by ELISA assays
Measured: Day 28+2
Geometric mean titers (GMTs)
salivary IgA (n=80), Serum IgA and IgG binding antibody titer by ELISA assays
Measured: Day 42±7
Geometric mean titers (GMTs)
salivary IgA (n=80), Serum IgA and IgG binding antibody titer by ELISA assays
Measured: Day 90±7
Geometric mean titers (GMTs)
salivary IgA (n=80), Serum IgA and IgG binding antibody titer by ELISA assays
Measured: Day 180±7
Geometric mean titres
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays.
Measured: baseline
Geometric mean titres
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays.
Measured: Day 28+2
Geometric mean titres
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays.
Measured: Day 42±7
adverse event
The occurrence of adverse event of special interest (AESI).
Measured: 180 Days
vaccine induced thrombosis and thrombocytopenia
The occurrence of the vaccine induced thrombosis and thrombocytopenia in participants reporting the respective symptoms and signs.
Measured: 180 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2022
- Study start16 Apr 2022
- Primary completion19 Jul 2022
- Study completion28 Feb 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19 Respiratory InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3,160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bharat Biotech International Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05522335
- Sponsor's protocol ID
- BBIL/BBV154-III/2022
- Other IDs
- BBIL/BBV154-III/2022
- Acronym
- Nasal154PH3
- Status last verified
- Aug 2022
- First submitted
- 13 Aug 2022
- Last updated
- 31 Aug 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Singh C, Verma S, Reddy P, Diamond MS, Curiel DT, Patel C, Jain MK, Redkar SV, Bhate AS, Gundappa V, Konatham R, Toppo L, Joshi AC, Kushwaha JS, Singh AP, Bawankule S, Ella R, Prasad S, Ganneru B, Chiteti SR, Kataram S, Vadrevu KM. Phase III Pivotal comparative clinical trial of intranasal (iNCOVACC) and intramuscular COVID 19 vaccine (Covaxin(R)). NPJ Vaccines. 2023 Aug 18;8(1):125. doi: 10.1038/s41541-023-00717-8.
PubMed 37596281Nakahashi-Ouchida R, Fujihashi K, Kurashima Y, Yuki Y, Kiyono H. Nasal vaccines: solutions for respiratory infectious diseases. Trends Mol Med. 2023 Feb;29(2):124-140. doi: 10.1016/j.molmed.2022.10.009. Epub 2022 Nov 23.
PubMed 36435633
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized Open Label Multi-center Study to Compare Immunogenicity and Safety of BBV154 With COVAXIN®, and to Assess Lot to Lot Consistency of BBV154 in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT05522335
- Acronym / sponsor ID
- Nasal154PH3 / BBIL/BBV154-III/2022
- Conditions
- COVID-19 Respiratory Infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 3,160 participants (actual)
- Lead sponsor
- Bharat Biotech International LimitedIndustry (pharma, biotech, devices)
- Study start
- 16 Apr 2022 (actual)
- Primary completion
- 19 Jul 2022 (actual)
- Study completion
- 28 Feb 2023 (estimated)
- First posted
- 31 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Group 1 (BBV154): In this group, 3000 participants will be recruited, randomized in 1:1:1 ratio receive 3 consecutive lots (Lot 1: 1000, Lot 2: 1000, Lot 3: 1000) of the BBV154 vaccine (0.5 mL each dose) on day 0 and day 28 via intranasal route. Group 2 (COVAXIN®): In this group, 160 participants will be recruited and administered with COVAXIN® vaccine on day 0 and on day 28 via intramuscular route.
A total sample size of 3160 healthy volunteer's age's ≥18 years will be recruited in this study. BBV154-Subjects- Part 1 ( Immunogenicity Group)- First 640 Subjects BBV154-Subjects- Part 2 ( Safety Group)- (Remaining 2520 subjects) Visit 1: Baseline (Day 0) Visit 2 (Day 28+2) Visit 3 (Day 42 ± 7 days) Visit 4 (Day 90 ± 7 days) and Visit 5 (Day 180± 7 days)
Detailed description
Sample Collection:
- Pregnancy test will be conducted by using rapid test kit.
- Immunogenicity analysis: A total of 5 ml of blood is collected on Day 0, Day 28+2, Day 42±7, Day 90±7 and Day 180±7 (Subset of 640, 160 from each lot and control group). Sera will collect from the blood sample and stored as 3 aliquots at -20°C.
- A saliva sample (5 mL) and an additional blood sample (10mL) will be collected on Day 0, Day 28+2, Day 42±7, Day 90±7 and Day 180±7 (Subset of 80, 60 from Group 1(20 from each lot) and 20 from Group 2).
- Saliva will be collected by Passive droll method using Falcon tube.
Sample Size:
A total sample size of 3160 healthy volunteer's age's ≥18 years will be recruited in this study.
Randomization:
A total of 3000 participants will be randomized in to BBV154 two-dose study arm and 160 participants in the COVAXIN® two-dose arm. The first 640 participants are randomized with block size 4, in 1:1:1:1 ratio [(3 (BBV154): 1 (COVAXIN®)].
Remaining 2520 participants in the study are randomized with the block size 6 in 1:1:1 ratio (BBV154).
STUDY RATIONALE:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is accelerating globally, leading to an increase in morbidity and mortality. The high-risk group includes the health care workers (HCW) (physicians and paramedical staff), working amid SARS-CoV-2 infected patients, all other people including household contacts of COVID-19 confirmed patients, people currently residing or working in COVID-19 hot-spots/outbreak areas where there is a high risk of transmission of SARS-CoV-2 infection and especially the elderly people (age >60 Years). Though SARS-CoV-2 infection may cause mild symptoms in many, nearly 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit (ICU). In severe cases, COVID-19 can be complicated by acute respiratory distress syndrome, sepsis, septic shock, and multi organ failure (2,3).
Though the antiviral drugs such as Remdesivir has been approved for COVID-19 treatment by USFDA, but it fails to prevent COVID-19 deaths (3). Hence, there is a necessity to develop a vaccine to prevent SARS-CoV-2 infection. Various types of COVID-19 vaccines, such as DNA, RNA based formulations, recombinant subunit vaccines containing the viral protein (Spike) epitopes, vector-based mutations (eg: Adenovirus and traditional inactivated vaccines are under development(6-9). A chimpanzee adenoviral vaccine (Adenoviral vectored-SARS-CoV-2-S), encoding prefusion stabilized spike protein of SARS-CoV-2 virus was developed by Washington University School of Medicine, and evaluated the protective activity of the vaccine in challenge studies with SARS-CoV-2 virus and mice expressing human angiotensin-converting enzyme 2 (ACE2) receptor(10). Challenge study results were revealed that intramuscular dosing of Adenoviral vectored-SARS-CoV-2-S vaccine induces systemic humoral and cell mediated immunity and protects against lung infection whereas intranasal dosing of the same vaccine induces both systemic and mucosal immunoglobulins (IgG and IgA) ad protects from lower and upper respiratory tract infections (10). Bharat Biotech has collaborated with Washington University to manufacture the vaccine and conduct clinical trials.
BBV154 intranasal vaccine was evaluated for its safety and immunogenicity in a Phase 1 clinical study in 175 healthy participants and found to be safe and immunogenic with two dose regimen administered with 4 weeks interval. In a Phase 2/3 clinical study, BBV154 vaccine with two dose regimen is further evaluating in 152 participants for its safety and immunogenicity. Bharat Biotech has designed this pivotal Phase 3 study to immunogenicity, safety and lot- to-lot consistency of the BBV154 vaccine compared to COVAXIN® vaccine.
STUDY DESIGN:
The Phase-III study is designed to evaluate the immunogenicity, safety and lot-to-lot consistency of two groups of healthy volunteers who receive either BBV154 vaccine via intranasal route or COVAXIN® vaccine via intramuscular route. A total of 3160 participants will be enrolled and assess for the safety, immunogenicity and lot consistency.
Group 1 (BBV154): In this group, 3000 participants will be recruited, randomized in 1:1:1 ratio receive 3 consecutive lots (Lot 1: 1000, Lot 2: 1000, Lot 3: 1000) of the BBV154 vaccine (0.5 mL each dose) on day 0 and day 28 via intranasal route.
Group 2 (COVAXIN®): In this group, 160 participants will be recruited and administered with COVAXIN® vaccine on day 0 and on day 28 via intramuscular route.
STUDY PROCEDURES
Visit 1: Baseline (Day 0):
- The participant will be screened for eligibility based on medical history, vitals, and physical examination and urine pregnancy test for female participants.
- If the participant is eligible (in good general health or stable pre-existing disease as per the discretion of the Principal investigator), a blood sample will be withdrawn prior to vaccination (Subset).
- Blood sample (5 mL) will be collected from subset (n=640, 160 from each lot of Group 1 \& Group 2) of participants.
- Saliva sample (5 mL) will be collected from subset (n=80, 60 from Group 1 (20 from each lot) and 20 from Group 2) of participants.
- An additional 10 mL of blood sample will be collected from subset (n=80, 60 from Group 1 (20 from each lot) and 20 from Group 2) of participants.
- An intranasal vaccine or COVAXIN® will be administered. Following vaccination, participants will remain at the study site for at least 30 minutes of observation to record any immediate adverse event.
- Diary card will be distributed to the participants.
- Telephonic follow-up (7-days post-vaccination) for adverse event recording. Visit 2 (Day 28+2):
- Study participants will return to the OPD for vitals and physical examination (general and systemic examination and urine pregnancy test for female participants), and specific symptoms for COVID-19.
- Blood sample (5 mL) will be collected from subset (n=640, 160 from each lot of Group 1 \& Group 2) of participants.
- Saliva sample (5 mL) will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- An additional 10 mL of blood sample will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- An intranasal vaccine or COVAXIN® will be administered. Following vaccination, participants will remain at the study site for at least 30 minutes of observation to record any adverse event.
- Diary card will be collected and a new diary card distributed to the participants.
- Telephonic follow-up (7-days post-vaccination) for adverse event recording.
Visit 3 (Day 42 ± 7 days):
- Study participants will return to the OPD for physical examination (general and systemic examination and urine pregnancy test for female participants), and specific symptoms for COVID-19.
- Blood sample (5 mL) will be collected from subset (n=640, 160 from each lot of Group 1 \& Group 2) of participants.
- Saliva sample (5 mL) will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- An additional 10 mL of blood sample will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- Diary card will be collected from the participants.
Visit 4 (Day 90 ± 7 days):
- Study participants (Subset) will return to the OPD for physical examination (general and systemic examination), and specific symptoms for COVID-19.
- Urine pregnancy test for female participants (Immunogenicity subset)
- Blood sample (5 mL) will be collected from subset (n=640, 160 from each lot of Group 1 \& Group 2) of participants.
- Saliva sample (5 mL) will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- An additional 10 mL of blood sample will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- Safety data will be collected from all the participants through telephonically other than immunogenicity subset (Day 90 ± 7 days).
Visit 5 (Day 180± 7 days):
- Study participants (Subset) will return to the OPD for physical examination (general and systemic examination), and specific symptoms for COVID-19.
- Urine pregnancy test for female participants (Immunogenicity subset)
- Blood sample (5 mL) will be collected from subset (n=640, 160 from each lot of Group 1 \& Group 2) of participants.
- Saliva sample (5 mL) will be collected from subset (n=80, 60 from Group 1(20 from each lot) and 20 from Group 2) of participants.
- An additional 10 mL of blood sample will be collected from subset (n=80, 60 from Group 1 (20 from each lot) and 20 from Group 2) of participants.
- Safety data will be collected from all the participants through telephonically other than immunogenicity subset (Day 180 ± 7 days).
Safety Monitoring:
Subjects will be observed for 30 minutes after vaccination for immediate adverse events. Active surveillance will be conducted for all participants for seven days after each dose of vaccine to ascertain information on solicited adverse events ("Reactogenicity"). Safety data will be collected from all the participants through telephonically on Day 90± 7 and 180± 7.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| BBV154 Lot-1 | Active comparator | Biological: BBV154(Intranasal) & covaxinSafety Group : In this group, 1000 participants will be recruited, receive BBV154 vaccine (0.5 mL each dose) on day 0 and day 28 via intranasal route and assess for the safety. |
| BBV154 Lot-2 | Active comparator | Biological: BBV154(Intranasal) & covaxinSafety Group : In this group, 1000 participants will be recruited, receive BBV154 vaccine (0.5 mL each dose) on day 0 and day 28 via intranasal route and assess for the safety. |
| BBV154 Lot-3 | Active comparator | Biological: BBV154(Intranasal) & covaxinSafety Group : In this group, 1000 participants will be recruited, receive BBV154 vaccine (0.5 mL each dose) on day 0 and day 28 via intranasal route and assess for the safety. |
| COVAXIN® | Active comparator | Biological: BBV154(Intranasal) & covaxinImmunogenicity Group :In this group, 160 participants will be recruited, receive Covaxin vaccine (0.5 mL each dose) on day 0 and day 28 via intramuscular route and assess for the Immunogenicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Ability to provide written informed consent.
- Participants of either gender of age ≥18 years.
- 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).
- Expressed interest and availability to fulfill the study requirements.
- 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
Key exclusion criteria (16 listed)
- History of any other COVID-19 investigational/or licensed vaccination.
- 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).
- Temperature >38.0°C (100.4°F) or symptoms of an acute self limiting illness such as an upper respiratory infection or gastroenteritis within three days prior to each dose of vaccine.
- Medical problems because of alcohol or illicit drug use during the past 12 months.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BBV154(Intranasal) & covaxinIntervention Covaxin | Biological | BBV154 Lot-1, BBV154 Lot-2, BBV154 Lot-3, COVAXIN® |
Primary outcome
Geometric mean titres (GMTs
Time frame: baseline
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays.
Geometric mean titres (GMTs
Time frame: Day 28+2
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays.
Geometric mean titres (GMTs)
Time frame: Day 42±7
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays
Geometric mean titres (GMTs)
Time frame: Day 90±7
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays
Geometric mean titres (GMTs)
Time frame: Day 180±7.
Serum neutralising antibody titer (NAb"s) by neutralizing antibody assays
solicited adverse events
Time frame: 7days
The occurrence of solicited adverse events within seven days of vaccination
unsolicited adverse events
Time frame: day 180
The occurrence of any unsolicited adverse events up to day 180 from 1st dose vaccination.
10 secondary outcomes
Geometric mean titers (GMTs)
Time frame: baseline
Geometric mean titers (GMTs)
Time frame: Day 28+2
Geometric mean titers (GMTs)
Time frame: Day 42±7
Geometric mean titers (GMTs)
Time frame: Day 90±7
Geometric mean titers (GMTs)
Time frame: Day 180±7
Geometric mean titres
Time frame: baseline
Geometric mean titres
Time frame: Day 28+2
Geometric mean titres
Time frame: Day 42±7
adverse event
Time frame: 180 Days
vaccine induced thrombosis and thrombocytopenia
Time frame: 180 Days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2022.
- Derived from this study: PubMed 37596281Singh C, Verma S, Reddy P, Diamond MS, Curiel DT, Patel C, Jain MK, Redkar SV, Bhate AS, Gundappa V, Konatham R, Toppo L, Joshi AC, Kushwaha JS, Singh AP, Bawankule S, Ella R, Prasad S, Ganneru B, Chiteti SR, Kataram S, Vadrevu KM. Phase III Pivotal comparative clinical trial of intranasal (iNCOVACC) and intramuscular COVID 19 vaccine (Covaxin(R)). NPJ Vaccines. 2023 Aug 18;8(1):125. doi: 10.1038/s41541-023-00717-8.
- Derived from this study: PubMed 36435633Nakahashi-Ouchida R, Fujihashi K, Kurashima Y, Yuki Y, Kiyono H. Nasal vaccines: solutions for respiratory infectious diseases. Trends Mol Med. 2023 Feb;29(2):124-140. doi: 10.1016/j.molmed.2022.10.009. Epub 2022 Nov 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BBV154(Intranasal) & covaxin in people with COVID-19 Respiratory Infection, run by Bharat Biotech International Limited at 14 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 31 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Geometric mean titres (GMTs (time frame: baseline). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05522335, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2022.