BBV152/BBV154 Heterologus Prime-Boost Study
Condition: Corona Virus Infection
MeSH terms: Coronavirus Infections
Study type: Interventional
Phase: Phase 2

Summary: 
      All participants will be assessed for immunogenicity and safety endpoints and provide a blood
      sample before the administration of the first dose of IP. Blood samples will be collected on
      days 0, 9 (Groups 1, 3 and 4), 28,37 (Groups 2 and 4), 56, 90 and 180 to assess the
      neutralizing antibody titer against the SARSCoV-2 virus. A subset of 160 Participants (40
      participants from each group) will be assessed for immunogenicity analysis, among these
      subset 10mL of blood and 5mL of saliva will be collected on days 0, 9 (Groups 1, 3 and 4),
      28, 37 (Groups 2 and 4), 56, 90 and 180 to assess cell-mediated immunity and mucosal
      immunogenicity.

      Group 1 (COVAXIN® + COVAXIN®): In this group, 152 participants will be recruited who will
      receive COVAXIN® on day 0 and on day 28 via the intramuscular route.

      Group 2 (COVAXIN® + BBV154): In this group, 152 participants will be recruited who will
      receive COVAXIN® (Intramuscular) on day 0 and BBV154 (Intranasal) day 28.

      *Post 56 days of vaccination, participants with seroconversion rate less than 3 folds will
      receive another dose of COVAXIN® viaintramuscular route.

      Group 3 (BBV154 + COVAXIN®): In this group, 152 participants will be recruited who will
      receive BBV154 (Intranasal) on day 0 and COVAXIN® (Intramuscular) on day 28.

      *Post 56 days of vaccination, participants with seroconversion rate less than 3 folds will
      receive another dose of COVAXIN® via intramuscular route.

      Group 4 (BBV154 + BBV154): In this group, 152 participants will be recruited who will receive
      BBV154 on day 0 and on day 28 via the intranasal route.
    

Detailed description: 
      A Phase 2 randomized, multi-centric, Clinical Trial of Heterologus Prime-Boost Combination of
      SARS-CoV-2 Vaccines to evaluate the immunogenicity and safety of BBV152 (COVAXIN®) with
      BBV154 (Adenoviral Intranasal COVID-19 vaccine) in Healthy Volunteers.

      This is a heterologus prime boost study, designed to evaluate the immunogenicity and safety
      of COVAXIN® with BBV154 and vice versa, amongthe four groups. A total of 608 subjects will be
      enrolled in the 1:1:1:1 ratio.

      Group 1 (COVAXIN® + COVAXIN®): In this group, 152 participants will be recruited who will
      receive COVAXIN® on day 0 and on day 28 via the intramuscular route.

      Group 2 (COVAXIN® + BBV154): In this group, 152 participants will be recruited who will
      receive COVAXIN® (Intramuscular) on day 0 and BBV154 (Intranasal) day 28.

      *Post 56 days of vaccination, participants with seroconversion rate less than 3 folds will
      receive another dose of COVAXIN® viaintramuscular route

      Group 3 (BBV154 + COVAXIN®): In this group, 152 participants will be recruited who will
      receive BBV154 (Intranasal) on day 0 and COVAXIN® (Intramuscular) on day 28.

      *Post 56 days of vaccination, participants with seroconversion rate less than 3 folds will
      receive another dose of COVAXIN® via intramuscular route.

      Group 4 (BBV154 + BBV154): In this group, 152 participants will be recruited who will receive
      BBV154 on day 0 and on day 28 via the intranasal route.

      All participants will be assessed for immunogenicity and safety endpoints and provide a blood
      sample before the administration of the first dose of IP. Blood samples will be collected on
      days 0, 9 (Groups 1, 3 and 4), 28, 37 (Groups 2 and 4),56, 90 and 180 to assess the
      neutralizing antibody titer against the SARS-CoV-2 virus. A subset of 160 Participants (40
      participants from each group) will be assessed for cell mediated and mucosal immunogenicity
      analysis, among these subset 10mL of blood and 5mL of saliva will be collected on days 0, 9
      (Groups 1, 3 and 4), 28, 37 (Groups 2 and 4), 56, 90 and 180 to assess cell-mediated immunity
      and mucosal immunogenicity.

      STUDY PROCEDURE

      Visit 1(Day 0)

        -  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
           before vaccination for all the participants.

        -  Safety Labs: An additional 15mL of blood will collected from half of the study
           population (76 from each group) to assess the safety at Day 0 and 56.

        -  A blood sample (5 mL) will be collected from all the participants for immunogenicity
           assessment. A study vaccine/comparator 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.

        -  Additional 10 mL blood will be collected from subset of 160 participants (Group1:40,
           Group-2:40, Group 3: 40 and Group 4: 40).

        -  A 5mL saliva sample will be collected from subset of 160 participants (Group-1:40,
           Group-2:40, Group 3: 40 and Group 4: 40).

        -  Vaccine will be administered.

        -  Diary cards will be distributed to the participants.

        -  Telephonic follow-up (1-7-days post-vaccination) for adverse event recording.

      Visit 2 (Day 9+2):

        -  Study participants will return to the OPD for physical examination (general and systemic
           examination), and specific symptoms for COVID-19.

        -  A blood sample (5 mL) will be collected from all the participants for immunogenicity
           assessment.

        -  Subset of Study participants (Group 1, 3 and 4) will return to the OPD for vitals and
           physical examination (general and systemic examination), and specific symptoms for
           COVID-19.

        -  Additional 10 mL blood will be collected from subset of (Groups 1, 3 and
           4)participants(Group-1:40, Group-2:40, Group 3: 40 and Group 4: 40).

        -  A 5mL saliva sample will be collected from subset of (Groups 1, 3 and 4)
           participants(Group-1:40, Group-2:40, Group 3: 40 and Group 4: 40).

      Visit 3 (Day 28 +2 ):

        -  Study participants will return to the OPD for vitals and physical examination (general
           and systemic examination), and specific symptoms for COVID-19.

        -  A blood sample (5 mL) will be collected from all the participants for immunogenicity
           assessment.

        -  Additional 10 mL blood will be collected from subset of 160 participants(Group1:40,
           Group-2:40, Group 3: 40 and Group 4: 40).

        -  A 5mL saliva sample will be collected fromsubset of 160 participants(Group-1:40,
           Group-2:40, Group 3: 40 and Group 4: 40).

        -  Vaccine will be administered.

        -  Telephonic follow-up (1-7-days post-vaccination) for adverse event recording.

      Visit 4 (Day 37±2):

        -  Study participants will return to the OPD for physical examination (general and systemic
           examination), and specific symptoms for COVID-19.

        -  A blood sample (5 mL) will be collected from all the participants for immunogenicity
           assessment.

        -  Subset of Study participants (Groups 2 and 4) will return to the OPD for vitals and
           physical examination (general and systemic examination), and specific symptoms for
           COVID-19.

        -  Additional 10 mL blood will be collected from subset of (Groups 2 and 4) participants
           (Group-1:40, Group-2:40, Group 3: 40 and Group 4: 40).

        -  A 5mL saliva sample will be collected from subset of (Groups 2 and 4) participants
           (Group-1:40, Group-2:40, Group 3: 40 and Group 4: 40).

      Visit 5 (Day 56+7):

        -  Study participants will return to the OPD for physical examination (general and systemic
           examination), and specific symptoms for COVID-19.

        -  Safety Labs: 15mL of blood will collected from half of the study population (76 from
           each group) to assess the safety.

        -  A blood sample (5 mL) will be collected from all the participants for immunogenicity
           assessment.

        -  Additional 10 mL blood will be collected from subset of 160 participants(Group1:40,
           Group-2:40, Group 3: 40 and Group 4: 40).

        -  A 5mL saliva sample will be collected from subset of 160 participants (Group-1:40,
           Group-2:40, Group 3: 40 and Group 4: 40).

      Visit 6 (Day 90+7):

        -  Study participants will return to the OPD for physical examination (general and systemic
           examination), and specific symptoms for COVID-19.

        -  A blood sample (5 mL) will be collected from all the participants for immunogenicity
           assessment.

        -  Additional 10 mL blood will be collected from subset of 160 participants(Group1:40,
           Group-2:40, Group 3: 40 and Group 4: 40).

        -  A 5mL saliva sample will be collected from subset of 160 participants(Group-1:40,
           Group-2:40, Group 3: 40 and Group 4: 40).

      Visit 7 (Day 180+7):

        -  Study participants will return to the OPD for physical examination (general and systemic
           examination), and specific symptoms for COVID-19.

        -  A blood sample (5 mL) will be collected from all the participants for immunogenicity
           assessment.

        -  Additional 10 mL blood will be collected from subset of 160 participants (Group1:40,
           Group-2:40, Group 3: 40 and Group 4: 40).

        -  A 5mL saliva sample will be collected from subset of 160 participants (Group-1:40,
           Group-2:40, Group 3: 40 and Group 4: 40).

      DSMB & report

      An interim report based on the safety and immunogenicity of the vaccineswill be notified to
      the Data safety monitoring board and Central Drugs Standard Control Organization (CDSCO),
      India, for further progressing theclinical development of the vaccine. This interim report
      will contain a detailed analysis of the data based on the primary and secondary objectives
      through Day 56 (Immunogenicity & Safety).
    

Intervention name(s): COVAXIN(BBV152); BBV154 Intranasal Vaccine
Intervention type(s): Biological; Biological
Intervention description(s): COVAXIN® on day 0 and on day 28 via the intramuscular route in GROUP 1. COVAXIN® (Intramuscular) on day 0 and BBV154 (Intranasal) day 28:GROUP 2; BBV154 (Intranasal) on day 0 and COVAXIN® (Intramuscular) on day 28: GROUP 3 BBV154 on day 0 and on day 28 via the intranasal route: GROUP 4
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Group 1 (COVAXIN® + COVAXIN®): In this group, 152 participants will be recruited who will receive COVAXIN® on day 0 and on day 28 via the intramuscular route.
Group 2 (COVAXIN® + BBV154): In this group, 152 participants will be recruited who will receive COVAXIN® (Intramuscular) on day 0 and BBV154 (Intranasal) day 28.
Post 56 days of vaccination, participants with seroconversion rate less than 3 folds will receive another dose of COVAXIN® viaintramuscular route.
Group 3 (BBV154 + COVAXIN®): In this group, 152 participants will be recruited who will receive BBV154 (Intranasal) on day 0 and COVAXIN® (Intramuscular) on day 28.
Post 56 days of vaccination, participants with seroconversion rate less than 3 folds will receive another dose of COVAXIN® via intramuscular route.
Group 4 (BBV154 + BBV154): In this group, 152 participants will be recruited who will receive BBV154 on day 0 and on day 28 via the intranasal route
Masking: Single (Participant)
Primary purpose: Prevention