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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Occurrence of adverse events and Serious Adverse events
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
盲法说明
Blinded vial
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
- •Signed written informed consent prior to inclusion in the study
- •Seronegative for Zika by ELISA
- •Dengue sero-negative at baseline by screening laboratory evaluation, confirmed by Dengue IgG by ELISA method for Group 1 participants
- •Dengue seropositive at baseline by screening laboratory evaluation, confirmed by Dengue IgG by ELISA method for Group 2 participants
- •Dengue vaccination or suffered from Dengue viral fever for Group 2 volunteers
- •No history of yellow fever vaccination
- •No history of vaccination to Japanese encephalitis vaccination
- •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.
- •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)
- •No history of clinically significant immunosuppressive or autoimmune disease.
- •Laboratory investigations must be within normal limits
- •Hemoglobin >10gm/dL
- •WBC (white blood cells) >4000/mm3
- •Platelets >100,000/mm3
- •Bilirubin and AST/ ALT <1.5 x ULN (upper limit of normal)
- •Creatinine <1.5 x ULN for the clinical laboratory
- •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).
- •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.
- •Willing to allow storage and future use of biological samples for Zika virus related research.
排除标准
- •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
- •Administration of any vaccine within 4 weeks of first dose
- •Administration of any monoclonal or polyclonal antibody product within 4 weeks of the first dose of BBV121 vaccination
- •Administration of any blood product within 3 months of first dose
- •Pregnancy or breast feeding or plans to become pregnant during the study
- •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
- •Immunosuppressive illness including hematologic malignancy, history of solid organ or bone marrow transplantation
- •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
- •Prior major surgery or any radiation therapy within 4 weeks of enrolment
- •Any pre-excitation syndromes, e.g., Wolff-Parkinson-White syndrome
- •Presence of a cardiac pacemaker or automatic implantable cardioverter defibrillator
- •Metal implants within 20 cm of the planned site(s) of injection
- •Presence of keloid scar formation or hypertrophic scar at the planned site(s) of injection
- •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
- •Blood donations/ losses within 2 months of screening
- •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)
- •Prior radiotherapy in 30 days or less
- •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
- •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:
- •i. Bilirubin >1.5 x ULN (upper limit of normal) ii. AST/ ALT >1.5 x ULN
- •Inadequate renal function at screening as defined by:
- •i. Creatinine >1.5 x ULN for the clinical laboratory
- •An unusual or abnormal diet, for whatever reason e.g. religious fasting
- •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
研究组 & 干预措施
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
干预措施: BBV121 (Biological)
BBV121-10 µg
BBV121: Each 0.5ml vial contain purified inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5ml
干预措施: BBV121 (Biological)
BBV121-5 µg
BBV121: Each 0.5ml vial contain purified inactivated Zika virus, alum, 2-PE and phosphate buffered saline qs to 0.5mL
干预措施: BBV121 (Biological)
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
干预措施: BBV121 (Biological)
结局指标
主要结局
Occurrence of adverse events and Serious Adverse events
时间窗: 12 months
safety
Occurrence of adverse events and Serious Adverse events
时间窗: 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
时间窗: 7 Days
safety
次要结局
- Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion(Day 56)
- Geometric mean titre estimated by 50% plaque reduction neutralization test(Day 365)
- Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion(Day 0)
- Geometric mean titre estimated by 50% plaque reduction neutralization test and four-fold seroconversion(Day 28)