Phase I Placebo-Controlled Study of the Infectivity, Safety and Immunogenicity of a Single Dose of a Recombinant Live-attenuated Respiratory Syncytial Virus Vaccine, RSV 6120/∆NS1, Lot RSV#018A, or RSV 6120/F1/G2/∆NS1, Lot RSV#016A, Delivered as Nose Drops to RSV-seropositive Children 12 to 59 Months of Age and RSV-seronegative Infants and Children 6 to 24 Months of Age
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Number of Participants With Solicited Adverse Events (AEs) by Grade (RSV-seropositive Participants)
研究概览
简要总结
The purpose of this study is to evaluate the infectivity, safety, and immunogenicity of a single dose of recombinant, live-attenuated respiratory syncytial virus (RSV) vaccines (RSV 6120/∆NS1 or RSV 6120/F1/G2/∆NS1) in RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24 months of age.
详细描述
This study will evaluate the infectivity, safety, and immunogenicity of a single dose of recombinant, live-attenuated respiratory syncytial virus (RSV) vaccines (RSV 6120/∆NS1 or RSV 6120/F1/G2/∆NS1) in RSV-seropositive children 12 to 59 months of age and RSV-seronegative infants and children 6 to 24 months of age.
The vaccines will be evaluated in a stepwise fashion beginning with RSV-seropositive children (Group 1) and proceeding sequentially in RSV-seronegative infants and children (Group 2). In each group, participants will be randomly assigned to receive a single dose of RSV 6120/∆NS1, RSV 6120/F1/G2/∆NS1, or placebo at Day 0.
Participants will be enrolled in the study between April 1 and October 31, outside of the RSV season. Group 1 participants will be followed for 28 days after inoculation, and Group 2 participants will remain on the study until they complete the post-RSV season visit between April 1 and April 30 in the calendar year following enrollment. The expected duration of the initial study is 28 days for Group 1 participants and between 6 and 13 months for Group 2 participants, depending upon time of enrollment.
Study visits for all participants may include clinical assessments, blood collection, and nasal washes or nasal swabs. Additionally, participants' parents or guardians will be contacted by study staff at various times during the study to monitor participants' health.
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)
入排标准
- 年龄范围
- 6 Months 至 59 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •FOR RSV-SEROPOSITIVE CHILDREN
- •Greater than or equal to 12 months of age and less than 60 months of age at the time of inoculation
- •Screening serum specimen for RSV-neutralizing antibody is obtained within the calendar year of inoculation
- •Seropositive for RSV antibody, defined as serum RSV-neutralizing antibody titer greater than or equal to 1:40
- •Pre-inoculation serum sample for RSV-neutralizing antibody specimen is obtained no more than 56 days prior to inoculation
- •In good health based on review of the medical record, history, and physical examination (PE) at the time of inoculation
- •Received routine immunizations appropriate for age based on the Advisory Committee on Immunization Practices (ACIP) Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger
- •Growing normally for age as demonstrated on a standard growth chart and has a current height and weight above the 3rd percentile for age
- •Expected to be available for the duration of the study
- •Parent/guardian is willing and able to provide written informed consent
排除标准
- •FOR RSV-SEROPOSITIVE CHILDREN
- •Born at less than 34 weeks gestation
- •Maternal history of positive human immunodeficiency virus (HIV) test
- •Evidence of chronic disease
- •Known or suspected impairment of immune function
- •Bone marrow/solid organ transplant recipient
- •Major congenital malformations, including congenital cleft palate or cytogenetic abnormalities
- •Suspected or documented developmental disorder, delay, or other developmental problem
- •Cardiac abnormality requiring treatment
- •Lung disease or reactive airway disease
- •More than one episode of wheezing in the first year of life
- •Wheezing episode or received bronchodilator therapy within the past 12 months
- •Wheezing episode or received bronchodilator therapy after the age of 12 months
- •Previous receipt of supplemental oxygen therapy in a home setting
- •Previous receipt of an investigational RSV vaccine
- •Previous receipt or planned administration of anti-RSV antibody product including ribavirin, RSV Ig or RSV mAb
- •Previous receipt of immunoglobulin or any antibody products within the past 6 months
- •Previous receipt of any other blood products within the past 6 months
- •Previous anaphylactic reaction
- •Previous vaccine-associated adverse reaction that was Grade 3 or above
- •Known hypersensitivity to any vaccine component
- •Member of a household that contains an infant who is less than 12 months of age at the date of inoculation through the 10th day after inoculation
- •Member of a household that, at the date of inoculation through the 10th day after inoculation, contains an immunocompromised individual including but not limited to:
- •a person who is HIV-infected
- •a person who has received chemotherapy within the 12 months prior to enrollment
- •a person receiving immunosuppressant agents
- •a person living with a solid organ or bone marrow transplant
- •Will attend a daycare facility that does not separate children by age and contains an infant who is less than 12 months of age at the date of inoculation through the 10th day after inoculation
- •Receipt of any of the following prior to enrollment:
- •any inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days prior, or
- •any live vaccine, other than rotavirus vaccine, within the 28 days prior, or
- •another investigational vaccine or investigational drug within 28 days prior, or
- •salicylate (aspirin) or salicylate-containing products within the past 28 days
- •Scheduled administration of any of the following after planned inoculation:
- •inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or
- •any live vaccine other than rotavirus within the 28 days after, or
- •another investigational vaccine or investigational drug within the 28 days after
- •Receipt of any of the following medications within 3 days of study enrollment:
- •systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or
- •intranasal medications, or
- •other prescription medications except the permitted concomitant medications listed in the protocol
- •Any of the following events at the time of enrollment:
- •fever (temporal or rectal temperature of greater than or equal to 100.4°F), or
- •upper respiratory signs or symptoms (rhinorrhea, cough, or pharyngitis) or
- •nasal congestion significant enough to interfere with successful inoculation, or
- •otitis media
- •INCLUSION CRITERIA FOR RSV-SERONEGATIVE INFANTS & CHILDREN
- •Greater than or equal to 6 months of age and less than 25 months of age at the time of inoculation
- •Screening and pre-inoculation serum specimens for RSV-neutralizing antibody are obtained no more than 42 days prior to inoculation
- •Seronegative for RSV antibody, defined as serum RSV-neutralizing antibody titer less than 1:40
- 另有 57 项未显示
研究组 & 干预措施
Group 1: RSV 6120/∆NS1 Vaccine
Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of 10^6.0 plaque-forming units (PFUs) of RSV 6120/∆NS1 vaccine at Day 0.
干预措施: RSV 6120/∆NS1 (Biological)
Group 1: RSV 6120/F1/G2/∆NS1 Vaccine
Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of 10^5.8 PFUs of RSV 6120/F1/G2/∆NS1 vaccine at Day 0.
干预措施: RSV 6120/F1/G2/∆NS1 (Biological)
Group 1: Placebo
Healthy RSV-seropositive children greater than or equal to 12 months to less than 60 months will receive a single dose of placebo at Day 0.
干预措施: Placebo (Biological)
Group 2: RSV 6120/∆NS1 Vaccine
Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of 10^5.0 PFUs of RSV 6120/∆NS1 vaccine at Day 0.
干预措施: RSV 6120/∆NS1 (Biological)
Group 2: RSV 6120/F1/G2/∆NS1
Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of 10^5.0 PFUs of RSV 6120/F1/G2/∆NS1 vaccine at Day 0.
干预措施: RSV 6120/F1/G2/∆NS1 (Biological)
Group 2: Placebo
Healthy RSV-seronegative infants and children greater than or equal to 6 months to less than 25 months will receive a single dose of placebo at Day 0.
干预措施: Placebo (Biological)
结局指标
主要结局
Number of Participants With Solicited Adverse Events (AEs) by Grade (RSV-seropositive Participants)
时间窗: Measured through Day 10
Solicited adverse events (AE's) include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI) as defined in Appendix IV of the protocol document. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (Grade 1-mild to Grade 4- life-threatening) following protocol-defined grading system outlined in Table 20 and 21 in the protocol document.
Number of Participants With Solicited Adverse Events (AEs) by Grade (RSV-seronegative Participants)
时间窗: Measured through Day 28
Solicited adverse events include fever; otitis media; upper respiratory illness (URI); lower respiratory illness (LRI) and cough (without LRI) as defined in Appendix IV of the protocol document. The number of participants who experienced solicited adverse events was presented. A participant was only counted once in each solicited AE category, and that is in the line corresponding to the highest grade adverse event they had in that category. These events were graded (grade 1- mild to Grade 4-life-threatening) following protocol-defined grading system outlined in Table 20 and Table 21 in the protocol document.
Number of Participants With Unsolicited AEs (RSV-seropositive Participants)
时间窗: Measured through Day 10
Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented.
Number of Participants With Unsolicited AEs (RSV-seronegative Participants)
时间窗: Measured through Day 28
Unsolicited adverse events were other events, not included in the solicited AEs. The number of participants who experienced unsolicited adverse events was presented.
Number of Participants With Serious Adverse Events (SAEs) (RSV-seropositive Participants)
时间窗: Measured through Day 28
A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that: * Results in death during the period of protocol-defined surveillance; * Is life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death were it more severe; * Requires inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting; * Results in a persistent or significant disability/incapacity; * Is a congenital anomaly or birth defect, OR * Is an important medical event that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes above.
Number of Participants With Serious Adverse Events (SAEs) (RSV-seronegative Participants)
时间窗: Measured through Day 56
A Serious Adverse Event (SAE) is an AE, whether considered related to the study product or not, that: * Results in death during the period of protocol-defined surveillance; * Is life threatening: defined as an event in which the patient was at immediate risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death were it more severe; * Requires inpatient hospitalization (or prolongation of existing hospitalization): defined as at least an overnight stay in the hospital or emergency ward for treatment that would have been inappropriate if administered in the outpatient setting; * Results in a persistent or significant disability/incapacity; * Is a congenital anomaly or birth defect, OR * Is an important medical event that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes above.
Frequency of Infection With RSV Vaccine Virus (RSV-seropositive Participants)
时间窗: Measured through Day 28
Defined as 1) vaccine virus identified in nasal wash (a binary outcome based on nasal washes or done throughout the study period; Day 0 nasal wash will be counted as baseline) or 2) a greater than or equal to 4-fold rise in serum RSV neutralizing antibody titer or serum RSV F (IgG) titer from study entry to Study Day 28.
Frequency of Infection With RSV Vaccine Virus (RSV-seronegative Participants)
时间窗: Measured through Day 56
Defined as 1) vaccine virus identified in nasal wash or nasal swab (a binary outcome based on nasal washes or nasal swabs done throughout the study period; Day 0 nasal wash or nasal swabs will be counted as baseline) or 2) a greater than or equal to 4-fold rise in serum RSV neutralizing antibody titer or serum RSV F (IgG) titer from study entry to Study Day 56.
Peak Titer of Vaccine Virus Shed by Culture (RSV-seropositive Participants)
时间窗: Measured at Days 0,3,4,5,6,7 and 10.
This is the mean of the highest value per participant of the titer of vaccine virus shed. It was measured by culture. Only participants who met the definition of infection with vaccine virus were included.
Peak Titer of Vaccine Virus Shed by Culture (RSV-seronegative Participants)
时间窗: Measured at Days 0, 3, 5, 7, 10, 12, 14, 17 and 28
This is the mean of the highest value per participant of the titer of vaccine virus (peak titer) shed measured by culture from all samples collected during the acute phase. Only participants who met the definition of infection with vaccine virus were included.
Duration of Virus Shedding in Nasal Washes (RSV-seropositive Participants)
时间窗: Measured at Days 0, 3, 4, 5, 6, 7 and 10
As determined by a) culture and b) reverse transcription polymerase chain reaction (rRT-PCR)
Duration of Virus Shedding in Nasal Washes or Nasal Swabs (RSV-seronegative Participants)
时间窗: Measured at Days 0,3,5,7,10,12,14,17 and 28. Last day positive is reported.
As determined by a) culture and/or b) qPCR. Only the participants who met the definition of infection with vaccine virus were included.
Number of Participants With a Greater Than or Equal to 4-fold Rise in Serum RSV-Neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein (RSV-seropositive Participants)
时间窗: Measured at Day 0 and Day 28
Serum RSV-neutralizing antibody titers were assessed through an Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.
Number of Participants With a Greater Than or Equal To 4-fold Rise in Serum RSV-Neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein (RSV-seronegative Participants)
时间窗: Measured through Day 56
As defined as a greater than or equal to 4-fold rise in RSV Neutralizing Antibody Titer and/or Serum Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.
RSV-Neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Antibody Responses to RSV F Glycoprotein (RSV-seropositive Participants)
时间窗: Measured through Day 28
Serum RSV-neutralizing antibody titers to RSV F glycoprotein were assessed by glycoprotein Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined a a greater than or equal to 4-fold increase in titer in paired specimens, between pre-inoculation and post-inoculation time points.
RSV-neutralizing Serum Antibody Titer and Immunoglobulin G (IgG) Antibody Responses to RSV F Glycoprotein (RSV-seronegative Participants)
时间窗: Measured through Day 56
Serum Antibody Titers to RSV F Glycoprotein were assessed by Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA). Antibody responses were defined as a greater than or equal to 4-fold increase in titer paired specimens, between pre-inoculation and post-inoculation time points.
The Frequency of Study-related Product Lower Respiratory Tract Illness (LRIs) in RSV-seropositive Participants.
时间窗: Day 0 through the 28th day following inoculation
Lower respiratory tract illness (LRI) is a Solicited Adverse Event (AE) as defined in Appendix IV of the protocol document. LRI includes: wheezing, pneumonia, laryngotracheobronchitis (croup), rhonchi, rales. The number of participants who experienced LRI was presented.
次要结局
- Number of Participants With Greater Than or Equal to 4-fold Rise in Serum RSV-neutralizing Antibody Titers and/or Serum Antibody Titers to RSV F Glycoprotein in RSV-seronegative Subjects (Group 2) Infected With Wt-RSV During the RSV Surveillance(Measured pre-RSV Surveillance period (baseline) and post-RSV Surveillance period (4-6 months after the baseline))
- Frequency of Symptomatic, Medically Attended Respiratory and Febrile Illness in the RSV-seronegative (Group 2) Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the RSV Season(Measured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study)
- Severity of Symptomatic, Medically Attended Respiratory and Febrile Illness in the RSV-seronegative (Group 2) Vaccine and Placebo Recipients Who Experience Natural Infection With wt RSV During the RSV Season.(Measured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study)
- Serum RSV Antibody Titers and Immunoglobulin G (IgG) Serum Antibody Titers to RSV F Glycoprotein Enzyme-linked Immunosorbent Assay (ELISA) in RSV Seronegative Subjects (Group 2) Infected With Wt-RSV During the RSV Surveillance.(Measured through participants' last study visit at 6 to 13 months, depending on when participants enroll in the study)