Clinical trial NCT04478656: Safety and Immunogenicity of BBV121
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Zika Virus Infection
Lead sponsor: Bharat Biotech International Limited
Sponsor class: INDUSTRY
First posted: 2020-07-21
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Occurrence of adverse events and Serious Adverse events
timeFrame: Within 2 hrs
measure: Occurrence of adverse events and Serious Adverse events
timeFrame: 7 Days
measure: Occurrence of adverse events and Serious Adverse events
timeFrame: 12 months
Secondary outcomes:
measure: Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion
timeFrame: Day 0
measure: Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion
timeFrame: Day 28
measure: Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion
timeFrame: Day 56
measure: Geometric mean titre estimated by 50% plaque reduction neutralization test
timeFrame: Day 365
Other outcomes:
Locations:
city: Hyderabad
country: India
facility: Bharat Biotech International Ltd
state: Telangana
Study officials:
affiliation: Bharat Biotech International Limited
name: Sudhakar Bangera
role: STUDY_CHAIR
References: