Zika: Safety and Immunogenicity of BBV121
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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 |
Biological: BBV121
BBV121 or Placebo are administered intramuscularly in deltoid region on Day 0 and 28
Other Names:
|
| 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 |
Biological: BBV121
BBV121 or Placebo are administered intramuscularly in deltoid region on Day 0 and 28
Other Names:
|
| 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 |
Biological: BBV121
BBV121 or Placebo are administered intramuscularly in deltoid region on Day 0 and 28
Other Names:
|
| 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 |
Biological: BBV121
BBV121 or Placebo are administered intramuscularly in deltoid region on Day 0 and 28
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Occurrence of adverse events and Serious Adverse events [Within 2 hrs]
safety Incidence of solicited AEs post-vaccination Incidence of unsolicited AEs post-vaccination Incidence of SAE
- Occurrence of adverse events and Serious Adverse events [7 Days]
safety
- Occurrence of adverse events and Serious Adverse events [12 months]
safety
Secondary Outcome Measures
- Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion [Day 0]
Immunogenicity
- Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion [Day 28]
Immunogenicity
- Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion [Day 56]
Immunogenicity
- Geometric mean titre estimated by 50% plaque reduction neutralization test [Day 365]
Immunogenicity
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Normal healthy male and female volunteers aged between 18 and 65 years weighing at least 50kgs of body weight
-
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
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Signed written informed consent prior to inclusion in the study
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Seronegative for Zika by ELISA
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Dengue sero-negative at baseline by screening laboratory evaluation, confirmed by Dengue IgG by ELISA method for Group 1 participants
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Dengue seropositive at baseline by screening laboratory evaluation, confirmed by Dengue IgG by ELISA method for Group 2 participants
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Dengue vaccination or suffered from Dengue viral fever for Group 2 volunteers
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No history of yellow fever vaccination
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No history of vaccination to Japanese encephalitis vaccination
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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.
-
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.
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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)
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No history of clinically significant immunosuppressive or autoimmune disease.
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Laboratory investigations must be within normal limits
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Hemoglobin >10gm/dL
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WBC (white blood cells) >4000/mm3
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Platelets >100,000/mm3
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Bilirubin and AST/ ALT <1.5 x ULN (upper limit of normal)
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Creatinine <1.5 x ULN for the clinical laboratory
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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).
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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.
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Willing to allow storage and future use of biological samples for Zika virus related research.
Exclusion Criteria:
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Administration of an investigational vaccine or drug either currently or within 30 days of first BBV121 vaccination
-
Previous receipt of an investigational vaccine or drug for the treatment or prevention of Zika virus
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Administration of any vaccine within 4 weeks of first dose
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Administration of any monoclonal or polyclonal antibody product within 4 weeks of the first dose of BBV121 vaccination
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Administration of any blood product within 3 months of first dose
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Pregnancy or breast feeding or plans to become pregnant during the study
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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
-
Positive serologic test for hepatitis C (exception: successful treatment with confirmation of sustained virologic response);
-
Chronic liver disease or cirrhosis
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Immunosuppressive illness including hematologic malignancy, history of solid organ or bone marrow transplantation
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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)
-
Current or anticipated treatment with TNF-alpha inhibitors such as infliximab, adalimumab, and etanercept
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Prior major surgery or any radiation therapy within 4 weeks of enrolment
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Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome
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Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator
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Metal implants within 20 cm of the planned site(s) of injection
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Presence of keloid scar formation or hypertrophic scar at the planned site(s) of injection
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Prisoner or participants who are compulsorily detained (involuntary incarceration) for treatment of either a physical or psychiatric illness
-
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
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Blood donations/ losses within 2 months of screening
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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)
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Prior radiotherapy in 30 days or less
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Significant pre-existing co-morbidities i. Cardiovascular
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Myocardial infarction within the last 6 months
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Congestive heart failure
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Unstable angina
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Active cardiomyopathy
-
Cardiac arrhythmia
-
Uncontrolled hypertension
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History of familial long QT syndrome or sudden cardiac death ii. Pulmonary disease requiring oxygen iii. Neurologic and psychiatric
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History of significant neurologic or psychiatric disorder that would preclude study compliance or ability to give informed consent iv. Rheumatic arthralgia
-
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
-
Inadequate hepatic function at screening as defined by:
- Bilirubin >1.5 x ULN (upper limit of normal) ii. AST/ ALT >1.5 x ULN
- Inadequate renal function at screening as defined by:
- Creatinine >1.5 x ULN for the clinical laboratory
-
An unusual or abnormal diet, for whatever reason e.g. religious fasting
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Bharat Biotech International Ltd | Hyderabad | Telangana | India | 500078 |
Sponsors and Collaborators
- Bharat Biotech International Limited
Investigators
- Study Chair: Sudhakar Bangera, Bharat Biotech International Limited
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BBIL/ZIKV/I/2016