Safety and Immunogenicity of BBV121 (Zika)

October 20, 2020 updated by: Bharat Biotech International Limited

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

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

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Telangana
      • Hyderabad, Telangana, India, 500078
        • Bharat Biotech International Ltd

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Normal healthy male and female volunteers aged between 18 and 65 years weighing at least 50kgs of body weight
  2. Ability to comprehend the full nature and purpose of the study, including possible risks and adverse events; ability to co-operate with the Investigator and to comply with the requirements of the entire study
  3. Signed written informed consent prior to inclusion in the study
  4. Seronegative for Zika by ELISA
  5. Dengue sero-negative at baseline by screening laboratory evaluation, confirmed by Dengue IgG by ELISA method for Group 1 participants
  6. Dengue seropositive at baseline by screening laboratory evaluation, confirmed by Dengue IgG by ELISA method for Group 2 participants
  7. Dengue vaccination or suffered from Dengue viral fever for Group 2 volunteers
  8. No history of yellow fever vaccination
  9. No history of vaccination to Japanese encephalitis vaccination
  10. Since active (live) ZIKV infection is known to cause teratogenicity, women of child-bearing potential should agree to use medically effective contraception (oral contraception, barrier methods, spermicide, etc.), preferably double contraception or have a partner who is sterile from enrollment to 3 months following the last injection, or have a male partner who is medically unable to induce pregnancy.
  11. Sexually active men who are considered sexually fertile must agree to use either a barrier method of contraception, preferably double contraception during the study, and agree to continue the use for at least 3 months following the last injection, or have a partner who is permanently sterile or is medically unable to become pregnant.
  12. A negative urine or serum pregnancy test before administration of investigational vaccine on day of screening (Serum Pregnancy Test), and Day 0 and Day 28 (both days Urine Pregnancy Test)
  13. No history of clinically significant immunosuppressive or autoimmune disease.
  14. Laboratory investigations must be within normal limits

    1. Hemoglobin >10gm/dL
    2. WBC (white blood cells) >4000/mm3
    3. Platelets >100,000/mm3
    4. Bilirubin and AST/ ALT <1.5 x ULN (upper limit of normal)
    5. Creatinine <1.5 x ULN for the clinical laboratory
  15. Not currently or within the previous 4 weeks taking immunosuppressive agents (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or corticosteroids at a dose less than 20 mg/day).
  16. Patients should be otherwise healthy as determined by physical examination, medical history, and no significant abnormality in any of the clinical parameters including ECG and Chest X-ray.
  17. Willing to allow storage and future use of biological samples for Zika virus related research.

Exclusion Criteria:

  1. Administration of an investigational vaccine or drug either currently or within 30 days of first BBV121 vaccination
  2. Previous receipt of an investigational vaccine or drug for the treatment or prevention of Zika virus
  3. Administration of any vaccine within 4 weeks of first dose
  4. Administration of any monoclonal or polyclonal antibody product within 4 weeks of the first dose of BBV121 vaccination
  5. Administration of any blood product within 3 months of first dose
  6. Pregnancy or breast feeding or plans to become pregnant during the study
  7. Positive serologic test for HIV, hepatitis B surface antigen (HBsAg); or any potentially communicable infectious disease as determined by the Principal Investigator or Medical Monitor
  8. Positive serologic test for hepatitis C (exception: successful treatment with confirmation of sustained virologic response);
  9. Chronic liver disease or cirrhosis
  10. Immunosuppressive illness including hematologic malignancy, history of solid organ or bone marrow transplantation
  11. Current or anticipated concomitant immunosuppressive therapy (excluding inhaled, topical skin and/or eye drop-containing corticosteroids, low-dose methotrexate, or corticosteroids at a dose less than 20 mg/day)
  12. Current or anticipated treatment with TNF-alpha inhibitors such as infliximab, adalimumab, and etanercept
  13. Prior major surgery or any radiation therapy within 4 weeks of enrolment
  14. Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome
  15. Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator
  16. Metal implants within 20 cm of the planned site(s) of injection
  17. Presence of keloid scar formation or hypertrophic scar at the planned site(s) of injection
  18. Prisoner or participants who are compulsorily detained (involuntary incarceration) for treatment of either a physical or psychiatric illness
  19. Active addictive drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements or assessment of immunologic endpoints
  20. Blood donations/ losses within 2 months of screening
  21. Significant orthostatic hypotension (i.e., a drop in systolic blood pressure of 30 mm Hg or more and/or a drop in diastolic blood pressure of 20 mmHg or more on standing)
  22. Prior radiotherapy in 30 days or less
  23. Significant pre-existing co-morbidities i. Cardiovascular

    • Myocardial infarction within the last 6 months
    • Congestive heart failure
    • Unstable angina
    • Active cardiomyopathy
    • Cardiac arrhythmia
    • Uncontrolled hypertension
    • History of familial long QT syndrome or sudden cardiac death ii. Pulmonary disease requiring oxygen iii. Neurologic and psychiatric
    • History of significant neurologic or psychiatric disorder that would preclude study compliance or ability to give informed consent iv. Rheumatic arthralgia
  24. Participants not having adequate hematologic reserve i. Hemoglobin <10gm/dL ii. WBC (white blood cells) <4000/mm3 iii. ANC (absolute neutrophils count) <2000/ mm3 iv. Platelets <100,000/mm3
  25. Inadequate hepatic function at screening as defined by:

    i. Bilirubin >1.5 x ULN (upper limit of normal) ii. AST/ ALT >1.5 x ULN

  26. Inadequate renal function at screening as defined by:

    i. Creatinine >1.5 x ULN for the clinical laboratory

  27. An unusual or abnormal diet, for whatever reason e.g. religious fasting
  28. Any illness or condition that in the opinion of the investigator may affect the safety of the participant or the evaluation of any study endpoint

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: BBV121-2.5 µg
BBV121: Each 0.5ml vial contain purified10 µg inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5mL
BBV121 or Placebo are administered intramuscularly in deltoid region on Day 0 and 28
Other Names:
  • Placebo
PLACEBO_COMPARATOR: Placebo
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
BBV121 or Placebo are administered intramuscularly in deltoid region on Day 0 and 28
Other Names:
  • Placebo
EXPERIMENTAL: BBV121-5 µg
BBV121: Each 0.5ml vial contain purified inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5mL
BBV121 or Placebo are administered intramuscularly in deltoid region on Day 0 and 28
Other Names:
  • Placebo
EXPERIMENTAL: BBV121-10 µg
BBV121: Each 0.5ml vial contain purified inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5ml
BBV121 or Placebo are administered intramuscularly in deltoid region on Day 0 and 28
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of adverse events and Serious Adverse events
Time Frame: Within 2 hrs

safety

  • Incidence of solicited AEs post-vaccination
  • Incidence of unsolicited AEs post-vaccination
  • Incidence of SAE
Within 2 hrs
Occurrence of adverse events and Serious Adverse events
Time Frame: 7 Days
safety
7 Days
Occurrence of adverse events and Serious Adverse events
Time Frame: 12 months
safety
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion
Time Frame: Day 0
Immunogenicity
Day 0
Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion
Time Frame: Day 28
Immunogenicity
Day 28
Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion
Time Frame: Day 56
Immunogenicity
Day 56
Geometric mean titre estimated by 50% plaque reduction neutralization test
Time Frame: Day 365
Immunogenicity
Day 365

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Sudhakar Bangera, Bharat Biotech International Limited

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 3, 2017

Primary Completion (ACTUAL)

November 15, 2017

Study Completion (ACTUAL)

November 15, 2018

Study Registration Dates

First Submitted

July 17, 2017

First Submitted That Met QC Criteria

July 15, 2020

First Posted (ACTUAL)

July 21, 2020

Study Record Updates

Last Update Posted (ACTUAL)

October 22, 2020

Last Update Submitted That Met QC Criteria

October 20, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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