<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04478656</url>
  </required_header>
  <id_info>
    <org_study_id>BBIL/ZIKV/I/2016</org_study_id>
    <nct_id>NCT04478656</nct_id>
  </id_info>
  <brief_title>Safety and Immunogenicity of BBV121</brief_title>
  <acronym>Zika</acronym>
  <official_title>Phase 1, Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial to Evaluate 2 Doses of 3 Sequentially Escalating Cohort of BBV121 in Healthy Adult Dengue Sero-Negative and Dengue Sero-Positive Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Bharat Biotech International Limited</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Bharat Biotech International Limited</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the safety, tolerability, and immunogenicity of two-doses of three-sequentially&#xD;
      escalating cohort (2.5 µg, 5 µg and 10 µg) of BBV121 (purified inactivated adsorbed Zika&#xD;
      virus vaccine) compared with Placebo (Alum). The investigational product is administered&#xD;
      intramuscularly on Day 0 and 28 with safety and immunogenicity testing on Day 0, 28 and 56,&#xD;
      and Month 6, 9 and 12&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A phase 1, multicenter, double-blind, placebo-controlled, randomised (intra group) clinical&#xD;
      trial to evaluate the safety, tolerability and immunogenicity of two-doses of&#xD;
      three-sequentially escalating cohort (2.5 µg, 5 µg and 10 µg) of BBV121 (inactivated adsorbed&#xD;
      Zika Virus Vaccine) compared with Placebo (Alum) administered intramuscularly on Day 0 and 28&#xD;
      in healthy adult Dengue Sero-Negative (Group 1) and Dengue Sero-Positive (Group 2) male and&#xD;
      female volunteers.&#xD;
&#xD;
      Participants will be assigned to sequential escalating dose level groups to receive&#xD;
      vaccinations at 2.5 µg, 5 µg, or 10 µg or Placebo on Day 0 and 28 with follow-up for 12&#xD;
      months from initial administration of the investigational product.&#xD;
&#xD;
      Immunogenicity testing on Day 0, 28 and 56, and post-study at the end of Month 6, 9 and 12&#xD;
      after the initial administration of the investigational product.&#xD;
&#xD;
      Safety tests (laboratory and clinical investigations) will be done during Screening, Day 0,&#xD;
      28, 56, and post-study at Month 6, 9 and 12 months after the initial administration of the&#xD;
      investigational product.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 3, 2017</start_date>
  <completion_date type="Actual">November 15, 2018</completion_date>
  <primary_completion_date type="Actual">November 15, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Participants will be assigned to sequential escalating dose level groups to receive vaccinations at 2.5 µg, 5 µg, or 10 µg or Placebo on Day 0 and 28 with follow-up for 12 months from initial administration of the investigational product.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Blinded vial</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of adverse events and Serious Adverse events</measure>
    <time_frame>Within 2 hrs</time_frame>
    <description>safety&#xD;
Incidence of solicited AEs post-vaccination&#xD;
Incidence of unsolicited AEs post-vaccination&#xD;
Incidence of SAE</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of adverse events and Serious Adverse events</measure>
    <time_frame>7 Days</time_frame>
    <description>safety</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of adverse events and Serious Adverse events</measure>
    <time_frame>12 months</time_frame>
    <description>safety</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion</measure>
    <time_frame>Day 0</time_frame>
    <description>Immunogenicity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion</measure>
    <time_frame>Day 28</time_frame>
    <description>Immunogenicity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion</measure>
    <time_frame>Day 56</time_frame>
    <description>Immunogenicity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Geometric mean titre estimated by 50% plaque reduction neutralization test</measure>
    <time_frame>Day 365</time_frame>
    <description>Immunogenicity</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Zika Virus Infection</condition>
  <arm_group>
    <arm_group_label>BBV121-2.5 µg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BBV121: Each 0.5ml vial contain purified10 µg inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5mL</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Each 0.5ml vial contain purified 2.5 µg, 5 µg or 10 µg inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5mL</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BBV121-5 µg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BBV121: Each 0.5ml vial contain purified inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5mL</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BBV121-10 µg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BBV121: Each 0.5ml vial contain purified inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5ml</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>BBV121</intervention_name>
    <description>BBV121 or Placebo are administered intramuscularly in deltoid region on Day 0 and 28</description>
    <arm_group_label>BBV121-10 µg</arm_group_label>
    <arm_group_label>BBV121-2.5 µg</arm_group_label>
    <arm_group_label>BBV121-5 µg</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Normal healthy male and female volunteers aged between 18 and 65 years weighing at&#xD;
             least 50kgs of body weight&#xD;
&#xD;
          2. Ability to comprehend the full nature and purpose of the study, including possible&#xD;
             risks and adverse events; ability to co-operate with the Investigator and to comply&#xD;
             with the requirements of the entire study&#xD;
&#xD;
          3. Signed written informed consent prior to inclusion in the study&#xD;
&#xD;
          4. Seronegative for Zika by ELISA&#xD;
&#xD;
          5. Dengue sero-negative at baseline by screening laboratory evaluation, confirmed by&#xD;
             Dengue IgG by ELISA method for Group 1 participants&#xD;
&#xD;
          6. Dengue seropositive at baseline by screening laboratory evaluation, confirmed by&#xD;
             Dengue IgG by ELISA method for Group 2 participants&#xD;
&#xD;
          7. Dengue vaccination or suffered from Dengue viral fever for Group 2 volunteers&#xD;
&#xD;
          8. No history of yellow fever vaccination&#xD;
&#xD;
          9. No history of vaccination to Japanese encephalitis vaccination&#xD;
&#xD;
         10. Since active (live) ZIKV infection is known to cause teratogenicity, women of&#xD;
             child-bearing potential should agree to use medically effective contraception (oral&#xD;
             contraception, barrier methods, spermicide, etc.), preferably double contraception or&#xD;
             have a partner who is sterile from enrollment to 3 months following the last&#xD;
             injection, or have a male partner who is medically unable to induce pregnancy.&#xD;
&#xD;
         11. Sexually active men who are considered sexually fertile must agree to use either a&#xD;
             barrier method of contraception, preferably double contraception during the study, and&#xD;
             agree to continue the use for at least 3 months following the last injection, or have&#xD;
             a partner who is permanently sterile or is medically unable to become pregnant.&#xD;
&#xD;
         12. A negative urine or serum pregnancy test before administration of investigational&#xD;
             vaccine on day of screening (Serum Pregnancy Test), and Day 0 and Day 28 (both days&#xD;
             Urine Pregnancy Test)&#xD;
&#xD;
         13. No history of clinically significant immunosuppressive or autoimmune disease.&#xD;
&#xD;
         14. Laboratory investigations must be within normal limits&#xD;
&#xD;
               1. Hemoglobin &gt;10gm/dL&#xD;
&#xD;
               2. WBC (white blood cells) &gt;4000/mm3&#xD;
&#xD;
               3. Platelets &gt;100,000/mm3&#xD;
&#xD;
               4. Bilirubin and AST/ ALT &lt;1.5 x ULN (upper limit of normal)&#xD;
&#xD;
               5. Creatinine &lt;1.5 x ULN for the clinical laboratory&#xD;
&#xD;
         15. Not currently or within the previous 4 weeks taking immunosuppressive agents&#xD;
             (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose&#xD;
             methotrexate, or corticosteroids at a dose less than 20 mg/day).&#xD;
&#xD;
         16. Patients should be otherwise healthy as determined by physical examination, medical&#xD;
             history, and no significant abnormality in any of the clinical parameters including&#xD;
             ECG and Chest X-ray.&#xD;
&#xD;
         17. Willing to allow storage and future use of biological samples for Zika virus related&#xD;
             research.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Administration of an investigational vaccine or drug either currently or within 30&#xD;
             days of first BBV121 vaccination&#xD;
&#xD;
          2. Previous receipt of an investigational vaccine or drug for the treatment or prevention&#xD;
             of Zika virus&#xD;
&#xD;
          3. Administration of any vaccine within 4 weeks of first dose&#xD;
&#xD;
          4. Administration of any monoclonal or polyclonal antibody product within 4 weeks of the&#xD;
             first dose of BBV121 vaccination&#xD;
&#xD;
          5. Administration of any blood product within 3 months of first dose&#xD;
&#xD;
          6. Pregnancy or breast feeding or plans to become pregnant during the study&#xD;
&#xD;
          7. Positive serologic test for HIV, hepatitis B surface antigen (HBsAg); or any&#xD;
             potentially communicable infectious disease as determined by the Principal&#xD;
             Investigator or Medical Monitor&#xD;
&#xD;
          8. Positive serologic test for hepatitis C (exception: successful treatment with&#xD;
             confirmation of sustained virologic response);&#xD;
&#xD;
          9. Chronic liver disease or cirrhosis&#xD;
&#xD;
         10. Immunosuppressive illness including hematologic malignancy, history of solid organ or&#xD;
             bone marrow transplantation&#xD;
&#xD;
         11. Current or anticipated concomitant immunosuppressive therapy (excluding inhaled,&#xD;
             topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or&#xD;
             corticosteroids at a dose less than 20 mg/day)&#xD;
&#xD;
         12. Current or anticipated treatment with TNF-alpha inhibitors such as infliximab,&#xD;
             adalimumab, and etanercept&#xD;
&#xD;
         13. Prior major surgery or any radiation therapy within 4 weeks of enrolment&#xD;
&#xD;
         14. Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome&#xD;
&#xD;
         15. Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator&#xD;
&#xD;
         16. Metal implants within 20 cm of the planned site(s) of injection&#xD;
&#xD;
         17. Presence of keloid scar formation or hypertrophic scar at the planned site(s) of&#xD;
             injection&#xD;
&#xD;
         18. Prisoner or participants who are compulsorily detained (involuntary incarceration) for&#xD;
             treatment of either a physical or psychiatric illness&#xD;
&#xD;
         19. Active addictive drug or alcohol use or dependence that, in the opinion of the&#xD;
             investigator, would interfere with adherence to study requirements or assessment of&#xD;
             immunologic endpoints&#xD;
&#xD;
         20. Blood donations/ losses within 2 months of screening&#xD;
&#xD;
         21. Significant orthostatic hypotension (i.e., a drop in systolic blood pressure of 30 mm&#xD;
             Hg or more and/or a drop in diastolic blood pressure of 20 mmHg or more on standing)&#xD;
&#xD;
         22. Prior radiotherapy in 30 days or less&#xD;
&#xD;
         23. Significant pre-existing co-morbidities i. Cardiovascular&#xD;
&#xD;
               -  Myocardial infarction within the last 6 months&#xD;
&#xD;
               -  Congestive heart failure&#xD;
&#xD;
               -  Unstable angina&#xD;
&#xD;
               -  Active cardiomyopathy&#xD;
&#xD;
               -  Cardiac arrhythmia&#xD;
&#xD;
               -  Uncontrolled hypertension&#xD;
&#xD;
               -  History of familial long QT syndrome or sudden cardiac death ii. Pulmonary&#xD;
                  disease requiring oxygen iii. Neurologic and psychiatric&#xD;
&#xD;
               -  History of significant neurologic or psychiatric disorder that would preclude&#xD;
                  study compliance or ability to give informed consent iv. Rheumatic arthralgia&#xD;
&#xD;
         24. Participants not having adequate hematologic reserve i. Hemoglobin &lt;10gm/dL ii. WBC&#xD;
             (white blood cells) &lt;4000/mm3 iii. ANC (absolute neutrophils count) &lt;2000/ mm3 iv.&#xD;
             Platelets &lt;100,000/mm3&#xD;
&#xD;
         25. Inadequate hepatic function at screening as defined by:&#xD;
&#xD;
             i. Bilirubin &gt;1.5 x ULN (upper limit of normal) ii. AST/ ALT &gt;1.5 x ULN&#xD;
&#xD;
         26. Inadequate renal function at screening as defined by:&#xD;
&#xD;
             i. Creatinine &gt;1.5 x ULN for the clinical laboratory&#xD;
&#xD;
         27. An unusual or abnormal diet, for whatever reason e.g. religious fasting&#xD;
&#xD;
         28. Any illness or condition that in the opinion of the investigator may affect the safety&#xD;
             of the participant or the evaluation of any study endpoint&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sudhakar Bangera</last_name>
    <role>Study Chair</role>
    <affiliation>Bharat Biotech International Limited</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Bharat Biotech International Ltd</name>
      <address>
        <city>Hyderabad</city>
        <state>Telangana</state>
        <zip>500078</zip>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>India</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>July 17, 2017</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>October 20, 2020</last_update_submitted>
  <last_update_submitted_qc>October 20, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 22, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Zika Virus Infection</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04478656
org study id: BBIL/ZIKV/I/2016
nct id: NCT04478656
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To evaluate the safety, tolerability, and immunogenicity of two-doses of three-sequentially
      escalating cohort (2.5 µg, 5 µg and 10 µg) of BBV121 (purified inactivated adsorbed Zika
      virus vaccine) compared with Placebo (Alum). The investigational product is administered
      intramuscularly on Day 0 and 28 with safety and immunogenicity testing on Day 0, 28 and 56,
      and Month 6, 9 and 12
A phase 1, multicenter, double-blind, placebo-controlled, randomised (intra group) clinical
      trial to evaluate the safety, tolerability and immunogenicity of two-doses of
      three-sequentially escalating cohort (2.5 µg, 5 µg and 10 µg) of BBV121 (inactivated adsorbed
      Zika Virus Vaccine) compared with Placebo (Alum) administered intramuscularly on Day 0 and 28
      in healthy adult Dengue Sero-Negative (Group 1) and Dengue Sero-Positive (Group 2) male and
      female volunteers.

      Participants will be assigned to sequential escalating dose level groups to receive
      vaccinations at 2.5 µg, 5 µg, or 10 µg or Placebo on Day 0 and 28 with follow-up for 12
      months from initial administration of the investigational product.

      Immunogenicity testing on Day 0, 28 and 56, and post-study at the end of Month 6, 9 and 12
      after the initial administration of the investigational product.

      Safety tests (laboratory and clinical investigations) will be done during Screening, Day 0,
      28, 56, and post-study at Month 6, 9 and 12 months after the initial administration of the
      investigational product.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be assigned to sequential escalating dose level groups to receive vaccinations at 2.5 µg, 5 µg, or 10 µg or Placebo on Day 0 and 28 with follow-up for 12 months from initial administration of the investigational product.
primary purpose: Prevention
masking: Double (Participant, Investigator)
masking description: Blinded vial
measure: Occurrence of adverse events and Serious Adverse events
time frame: Within 2 hrs
description: safety
Incidence of solicited AEs post-vaccination
Incidence of unsolicited AEs post-vaccination
Incidence of SAE
measure: Occurrence of adverse events and Serious Adverse events
time frame: 7 Days
description: safety
measure: Occurrence of adverse events and Serious Adverse events
time frame: 12 months
description: safety
measure: Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion
time frame: Day 0
description: Immunogenicity
measure: Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion
time frame: Day 28
description: Immunogenicity
measure: Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion
time frame: Day 56
description: Immunogenicity
measure: Geometric mean titre estimated by 50% plaque reduction neutralization test
time frame: Day 365
description: Immunogenicity
arm group label: BBV121-2.5 µg
arm group type: Experimental
description: BBV121: Each 0.5ml vial contain purified10 µg inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5mL
arm group label: Placebo
arm group type: Placebo Comparator
description: Each 0.5ml vial contain purified 2.5 µg, 5 µg or 10 µg inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5mL
arm group label: BBV121-5 µg
arm group type: Experimental
description: BBV121: Each 0.5ml vial contain purified inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5mL
arm group label: BBV121-10 µg
arm group type: Experimental
description: BBV121: Each 0.5ml vial contain purified inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5ml
intervention type: Biological
intervention name: BBV121
description: BBV121 or Placebo are administered intramuscularly in deltoid region on Day 0 and 28
arm group label: BBV121-10 µg
arm group label: BBV121-2.5 µg
arm group label: BBV121-5 µg
arm group label: Placebo
other name: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sudhakar Bangera
role: Study Chair
affiliation: Bharat Biotech International Limited
facility: 
country: India
responsible party type: Sponsor
mesh term: Zika Virus Infection
sharing ipd: No