An Efficacy and Safety Clinical Trial of an Investigational COVID-19 Vaccine (BBV152) in Adult Volunteers

An Event-Driven, Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate Efficacy, Safety, Immunogenicity, Lot-to-Lot Consistency of BBV152, a Whole-Virion Inactivated SARS-CoV-2 Vaccine in Adults≥18 Yrs of Age

The BBV152 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the efficacy, safety, and immunogenicity of BBV152 to prevent COVID-19 for up to 1 year after the second dose of BBV152.

This is a phase 3 Event-Driven, randomized, double-blind, placebo-controlled, multicentre study to Evaluate the Efficacy, Safety, and Immunogenicity of BBV152, a Whole-Virion Inactivated SARS-CoV-2 Vaccine in Volunteers aged 18 years and above.

A total of 25,800 subjects will be enrolled and randomized in a 1:1 ratio to receive the BBV152 vaccine and control. All participants will be assessed for efficacy and safety endpoints and provide a Nasopharyngeal(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 the 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. A safety follow-up will be done for all.

In addition, sites will be segregated based on the study objectives:

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 an 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 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 placebo) 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.

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.

Inclusion Criteria:

• Ability to provide written informed consent and availability to fulfill the study requirements.
• Participants of either gender of aged 18 years and above.
• 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.
• 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.
• 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.
• Agrees not to participate in another clinical trial at any time during the study period.
• Agrees not to take any COVID-19 licensed vaccination for the entire duration of the study.
• Agrees to remain in the study area for the entire duration of the study.
• Willing to allow storage and future use of biological samples for future research

Exclusion Criteria:

• History of any other COVID-19 investigational or licensed vaccination.
• Known history of SARS-CoV-2 infection, as declared by the subject.
• For women, positive urine pregnancy test before the first dose of vaccination, or any time during the study period.
• 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.
• Resident of COVID-19 infection in the same household.
• Known case of HIV, hepatitis B, or hepatitis C infection.
• Receipt of any licensed/experimental vaccine within four weeks before enrolment in this study.
• Receipt of immunoglobulin or other blood products within the three months before vaccination in this study.
• 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.
• Immunoglobulins, anti-cytokine antibodies, and blood products within 6 months prior to study vaccination, during, and 21 days following the last dose of vaccination.
• Pregnancy, lactation, or willingness/intention to become pregnant during the first 6 months after enrolment.
• Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, an endocrine disorder, and neurological illness (mild/moderate well-controlled comorbidities are allowed)

Re-Vaccination Exclusion Criteria

• Pregnancy.
• History of virologically (RT-PCR) confirmed SARS-CoV-2 infection
• Anaphylactic reaction following administration of the investigational vaccine.