Immunogenicity and Safety of a Purified Vero Rabies Vaccine - Serum Free in Comparison With Verorab® and Imovax® Rabies, in a Pre-exposure Regimen in Both Pediatric and Adult Populations and a Single Booster Dose of Purified Vero Rabies Vaccine - Serum Free Administered at 1 Year Post-3-dose Primary Series, and Between 2 up to 3 Years Post-One Week 2-Dose Primary Series in a Subset of Adults in Thailand
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,708
- 试验地点
- 4
- 主要终点
- Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 IU/mL
研究概览
简要总结
The primary objective of this study is:
To demonstrate the VRVg-2 is non-inferior to Verorab and Imovax Rabies vaccines in each age group (pediatric and adult populations) when administered as a 3-dose PrEP regimen, in terms of proportion of participants achieving a rabies virus neutralizing antibody (RVNA) titer ≥ 0.5 IU/mL at Day 42, ie. 14 days after the 3rd injection (for Primary Series Cohort 1).
The secondary objectives of this study are: First 1-5 with hypotheses testing will be evaluated sequentially - only if the previous objective is achieved, will the next objective be tested
To demonstrate that:
- the observed proportion of participants in the VRVg2(VRVg) group at D42 is at least 99% with a lower limit of the 95% confidence interval (CI) of at least 97%
- VRVg is non inferior (NI) to Verorab and Imovax Rabies vaccines (Imovax) in each age group at D28
- 2-dose VRVg at D28 is NI to 3-dose Imovax at D42 in each age group
- the observed proportion of participants in the VRVg group at D28 is at least 99% with a lower limit of the 95% CI of at least 97%
- 2-dose Imovax at D28 is NI to 3-dose Imovax at D42 in overall participants (Cohort1)
To describe:
- the immune response induced by VRVg versus Verorab and Imovax at D28 and at D42 in all age groups
- the immune response induced by VRVg at D14 after a booster dose of VRVg administered at M12 (Cohort1) and between M24 up to M36 (Cohort2)
- the persistence of immune response at M6,12,18, and pre-booster between M24 up to M36 post-primary series vaccination (Cohort2)
- safety profile of VRVg versus Verorab and Imovax in primary series and after a booster dose of VRVg
详细描述
The duration of each participant's participation in the primary series Cohort 1 of the study will be approximately 7 months (28 day-vaccination period followed by 6-month safety follow-up period). For the subset of adult participants in Booster Phase Cohort 1 who received a single booster dose of VRVg-2 (1 booster dose 365 days after primary series followed by 6-month safety follow-up period), the duration will be approximately 18 months.
For Primary Series Cohort 2, the duration of each participant's participation in the study will be approximately 7 months (one week vaccination period followed by 6-month safety follow-up period).
For the subset of adult participants in Immunogenicity Persistence and Booster Phase Cohort 2 who will be followed-up for evaluation of immunogenicity persistence after primary series (including blood samples collection at M6, M12, M18, and between 24 up to 36 months) and who will receive a single booster dose of VRVg-2 (after the blood sample collection between 24 up to 36 months), the duration will be approximately 30 to 42 months.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
For cohort 1 primary series and booster dose and cohort 2 primary series. The study is conducted in an observer-blind manner. Unblinded staff members, independent of the safety evaluation and other study evaluations, prepare and administer the vaccine. The Investigator or delegate in charge of safety assessment as well as the participants are blinded and do not know which vaccine is administered.
In addition to the participants, health care providers, data collectors, outcome assessors (eg, Investigator who assess the safety), the Sponsor personnel (eg, Clinician, Data Management, Biostatistician) will remain blinded until the first statistical analysis.
For cohort 2 immunogenicity persistence and booster phase This phase is open label, however, the laboratory analysts who will be involved in the blood sample testing will remain blinded during the whole study.
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged ≥1 year on the day of inclusion
- •Cohort 1 - pediatrics (>1 to 17 years old) and adult (≥18 years old)
- •Cohort 2 - all adults (≥18 years old)
- •Informed consent form has been signed and dated by the participant and /or and parent(s) or legally acceptable representative (LAR) and by an independent witness (if required by local regulations), as necessary; and assent form has been signed and dated by the participant, as required
- •Participant (adult ≥18 years) or participant and parent/LAR (1 year to <18 years) are able to attend all scheduled visits and to comply with all study procedures.
排除标准
- •Participant is pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until 1 month after each vaccination. To be considered of non-childbearing potential, a female must be pre-menarche or post-menopausal for at least 1 year, or surgically sterile.
- •Participation at the time of study enrollment or, planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.
- •Receipt of any vaccine in the 4 weeks (28 days) preceding the first study vaccination or planned receipt of any vaccine prior to Visit 5 for pediatric participants and adult participants in Cohort 1, and prior to Visit 4 for adult participants in Cohort
- •Previous vaccination against rabies (in pre- or post-exposure regimen) with either the study vaccines or another vaccine.
- •Bite by, or exposure to a potentially rabid animal in the previous 6 months with or without post-exposure prophylaxis.
- •Receipt of immune globulins, blood or blood-derived products in the past 3 months.
- •Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
- •At high risk for rabies exposure during the study.
- •Known systemic hypersensitivity to any of the study/control vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances.
- •Self-reported thrombocytopenia, contraindicating intramuscular vaccination.
- •Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination.
- •Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
- •Current alcohol or substance abuse that, in the opinion of the investigator, might interfere with the study conduct or completion.
- •Chronic illness(1) that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion.
- •Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
- •Personal history of Guillain-Barré syndrome.
- •Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
- •Chronic illness may include, but is not limited to, neurological, cardiopulmonary, gastrointestinal, renal, genitourinary, metabolic, hematologic, auto-immune, or psychiatric disorders or infection
研究组 & 干预措施
Group1:VRVg2 Cohort1(C1)-1ry Series:pediatric&adult participants-Booster:102 adult participants
VRVg-2, 3 injections at Day 0, Day 7, and Day 28
Booster dose of VRVg-2 for a subset of 102 adult participants at Month 12
干预措施: Purified vero rabies vaccine - serum free - VRVg-2 (Biological)
Group 2:Verorab C1-1ry Series:pediatric&adult participants-Booster Phase:34 adult participants
Verorab, 3 injections at Day 0, Day 7, and Day 28
Booster dose of VRVg-2 for a subset of 34 adult participants at Month 12
干预措施: Purified vero rabies vaccine - serum free - VRVg-2 (Biological)
Group 2:Verorab C1-1ry Series:pediatric&adult participants-Booster Phase:34 adult participants
Verorab, 3 injections at Day 0, Day 7, and Day 28
Booster dose of VRVg-2 for a subset of 34 adult participants at Month 12
干预措施: Purified inactivated rabies vaccine - Verorab® (Biological)
Group 3:Imovax Rabies C1-1ry Series:pediatric&adult participants-Booster Phase:34 adult participants
Imovax Rabies, 3 injections at Day 0, Day 7, and Day 28
Booster dose of VRVg-2 for a subset of 34 adult participants at Month 12
干预措施: Purified vero rabies vaccine - serum free - VRVg-2 (Biological)
Group 3:Imovax Rabies C1-1ry Series:pediatric&adult participants-Booster Phase:34 adult participants
Imovax Rabies, 3 injections at Day 0, Day 7, and Day 28
Booster dose of VRVg-2 for a subset of 34 adult participants at Month 12
干预措施: Purified inactivated rabies vaccine - Imovax® Rabies (Biological)
Group 4:VRVg-2 Cohort 2(C2)-1ry Series:Adult participants-Booster Phase:138 adult participants
VRVg-2, 2 injections at Day 0 and Day 7
Booster dose of VRVg-2 for a subset of 138 adult participants between Month 24 up to Month 36
干预措施: Purified vero rabies vaccine - serum free - VRVg-2 (Biological)
Group 5:Verorab C2-1ry Series:adult participants-Booster Phase:46 adult participants
Verorab, 2 injections at Day 0 and Day 7
Booster dose of VRVg-2 for a subset of 46 adult participants between Month 24 up to Month 36
干预措施: Purified vero rabies vaccine - serum free - VRVg-2 (Biological)
Group 5:Verorab C2-1ry Series:adult participants-Booster Phase:46 adult participants
Verorab, 2 injections at Day 0 and Day 7
Booster dose of VRVg-2 for a subset of 46 adult participants between Month 24 up to Month 36
干预措施: Purified inactivated rabies vaccine - Verorab® (Biological)
Group 6:Imovax Rabies C2-1ry Series:adult participants-Booster Phase:46 adult participants
Imovax Rabies, 2 injections at Day 0 and Day 7
Booster dose of VRVg-2 for a subset of 46 adult participants between Month 24 up to Month 36
干预措施: Purified vero rabies vaccine - serum free - VRVg-2 (Biological)
Group 6:Imovax Rabies C2-1ry Series:adult participants-Booster Phase:46 adult participants
Imovax Rabies, 2 injections at Day 0 and Day 7
Booster dose of VRVg-2 for a subset of 46 adult participants between Month 24 up to Month 36
干预措施: Purified inactivated rabies vaccine - Imovax® Rabies (Biological)
结局指标
主要结局
Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 IU/mL
时间窗: Day 42 (post-vaccination)
RVNA titer against rabies virus was assessed using the Rapid Fluorescent Focus Inhibition test (RFFIT) assay method.
次要结局
- Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population(Cohort 1: Day 0 (pre-vaccination), Day 28 (post-vaccination); Cohort 2: Day 0 (pre-vaccination) and Day 28 (post-vaccination))
- Primary Series Cohort 1: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization(Cohort 1: Day 0 (pre-vaccination), Day 28 and Day 42 (post-vaccination))
- Primary Series Cohort 2: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization(Cohort 2: Day 0 (pre-vaccination) and Day 28 (post-vaccination))
- Booster Phase: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers(Day 0 (pre-vaccination), Month 12 (pre-booster dose) and Month 12 + Day 14 (post-booster dose))
- Booster Phase: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization(Month 12 (pre-booster dose) and Month 12 + Day 14 (post-booster dose))
- Primary Series Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL(Cohort 2: Day 0 (pre-vaccination) and Day 28 (post-vaccination))
- Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL(Cohort 1: Day 0 (pre-vaccination), Day 28 and Day 42 (post-vaccination))
- Primary Series: Groups 1 and 4: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population - Superiority Analysis(Day 28 (post-vaccination))
- Primary Series Cohort 1 Group 3: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Non-Inferiority Analysis(Cohort 1: Day 28 and Day 42 (post-vaccination))
- Primary Series Cohort 1: Rabies Virus Neutralizing Antibody Geometric Mean Titers (GMTs) Against Rabies Virus(Cohort 1: Day 0 (pre-vaccination), Day 28 and Day 42 (post-vaccination))
- Primary Series Cohort 2: Rabies Virus Neutralizing Antibody Geometric Mean Titers (GMTs) Against Rabies Virus(Cohort 2: Day 0 (pre-vaccination) and Day 28 (post-vaccination))
- Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population (Groups 1 and 4) Versus Cohort 1: Group 3: Non-inferiority Analysis(Pooled Groups 1 and 4: Day 28 (post-vaccination) and Primary Series: Cohort-1 Group 3: Day 42 (post-vaccination))
- Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])(Cohort 1: Day 0 (pre-vaccination), Day 28 and Day 42 (post-vaccination))
- Primary Series Cohort 1: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers(Cohort 1: Day 0 (pre-vaccination), Day 28 and Day 42 (post-vaccination))
- Primary Series Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])(Cohort 2: Day 0 (pre-vaccination) and Day 28 (post-vaccination))
- Primary Series Cohort 2: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers(Cohort 2: Day 0 (pre-vaccination) and Day 28 (post-vaccination))
- Number of Participants With Immediate Unsolicited Adverse Events (AEs)(Within 30 minutes after any vaccination)
- Number of Participants With Solicited Injection Site Reactions(Within 7 Days after any vaccination)
- Number of Participants With Unsolicited Adverse Events(Within 28 Days after any vaccination)
- Booster Phase: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL(Month 12 (pre-booster dose) and Month 12 + Day 14 (post-booster dose))
- Booster Phase: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (LLOQ)(Month 12 (pre-booster dose) and Month 12 + Day 14 (post-booster dose))
- Number of Participants With Systemic Reactions(Within 7 Days after any vaccination)
- Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)(From Baseline (Day 0) up to 6 months after last vaccination (i.e., up to 7 months for Primary Series Cohorts 1 & 2 and up to Month 18 for Booster Phase, Cohort 1))
- Booster Phase: Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus(Month 12 (pre-booster dose) and Month 12 + Day 14 (post-booster dose))
- Booster Phase Cohort 2: Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus(Month 24 up to Month 36 (pre-booster dose) and Month 24 up to Month 36 + Day 14 (post-booster dose))
- Booster Phase Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL(Month 24 up to Month 36 (pre-booster dose) and Month 24 up to Month 36 + Day 14 (post-booster dose))
- Booster Phase Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])(Month 24 up to Month 36 (pre-booster dose) and Month 24 up to Month 36 + Day 14 (post-booster dose))
- Booster Phase Cohort 2: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers(Day 0 (pre-vaccination), Month 24 up to Month 36 (pre-booster dose) and Month 24 up to Month 36 + Day 14 (post-booster dose))
- Booster Phase Cohort 2: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization(Month 24 up to Month 36 (pre-booster dose) and Month 24 up to Month 36 + Day 14 (post-booster dose))
- Booster Phase Cohort 2: Number of Participants With Immediate Unsolicited Adverse Events (AEs)(Within 30 minutes after any vaccination)
- Booster Phase Cohort 2: Number of Participants With Systemic Reactions(Within 7 Days after any vaccination)
- Booster Phase Cohort 2: Number of Participants With Solicited Injection Site Reactions(Within 7 Days after any vaccination)
- Booster Phase Cohort 2: Number of Participants With Unsolicited Adverse Events(Within 28 Days after any vaccination)
- Booster Phase Cohort 2: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)(From Baseline (Day 0) up to 6 months after last vaccination (i.e., up to Month 42))