A Parallel Group, Phase III, Randomized, Observer Blind, Placebo Controlled, Multi Center, Multinational, Multi Arm Study to Demonstrate Non-inferiority of the Immune Response of a Low Dose Compared to the Standard Dose and to Evaluate the Safety of a Respiratory Syncytial Virus Vaccine in Infants and Toddlers (OPAL)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 42
- 试验地点
- 3
- 主要终点
- Cohort 2: Geometric Mean Titers (GMT) of RSV A Serum Neutralizing Antibodies at Day 85 (Post-Dose 2)
研究概览
简要总结
This study was a Phase III, parallel group, randomized, observer blind, placebo controlled, multi-national, multi-center, multi-arm study conducted in 42 healthy children enrolled at 6 months to <22 months of age. The purpose of the study was to evaluate the non-inferiority of the immune response of the lower dose (LD) when compared to the standard dose (SD) respiratory syncytial virus infant and toddler (RSVt) vaccine and the safety of the LD, SD and high dose (HD) vaccine in preterm born children and of the HD vaccine in full term born children administered by intranasal route and compared to placebo.
详细描述
The study duration was approximately 8 months for each participant, including the 6 months safety follow-up phone call after the second study intervention administration.
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
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
- Blinding for vaccine group assignment: participants, parents or legally acceptable representatives (LARs), outcome assessors, investigators, laboratory personnel, Sponsor study staff
- No blinding for study staff who prepare and administer the study interventions
入排标准
- 年龄范围
- 6 Months 至 21 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Aged 6 months to < 22 months on the day of inclusion (means from the day of the 6-month birthday to the day before the 22-month birthday. The second vaccine administration was administered before the study participant has turned 24 months of age).
- •Participants who were healthy as determined by medical evaluation including medical history.
- •For Cohort 1 and Cohort 2 (contingent upon satisfactory safety profile of the RSVt vaccine in Cohort 1):
- •-Participant born 28 through 36 weeks of gestation and medically stable as assessed by the investigator, based on the following definition: "Medically stable" refers to the condition of premature infants who do not require significant medical support or ongoing management for debilitating disease and who have demonstrated a clinical course of sustained recovery by the time they receive the first dose of study intervention.
- •For Cohort 2:
- •Participant born at full term of pregnancy (≥ 37 weeks of gestation).
排除标准
- •Participants were excluded from the study if any of the following criteria apply:
- •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).
- •Known systemic hypersensitivity to any of the study intervention components, or history of a life-threatening reaction to the study intervention used in the study or to a product containing any of the same substances.
- •Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion.
- •History of medically diagnosed wheezing. Children with a history of recurrent wheezing will be excluded. Children with a previous single episode of wheezing may be included if that episode of wheezing was not associated with hospitalization or if does not have a family history of wheezing.
- •Any acute febrile illness in the past 48 hours that according to investigator judgment is significant enough to interfere with successful inoculation on the day of vaccination. A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
- •Probable or confirmed ongoing case of viral respiratory infection (including COVID-19, influenza, rhinovirus, etc.) at the time of enrollment. A prospective participant should not be included in the study until the respiratory infection has resolved.
- •Member of a household that 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 study enrollment
- •a person who has received (within the past 6 months) or is receiving (at the time of enrollment) immunosuppressant agents
- •a person living with a solid organ or bone marrow transplant
- •Potential close contact with other immunocompromised individual within 30 days after each vaccination as per investigator's discretion.
- •Participant's biological mother's previous receipt or planned administration of an investigational RSV vaccine during pregnancy and/or breastfeeding.
- •Receipt or planned receipt of any of the following vaccines prior to enrollment or after the first study intervention administration:
- •Any other intranasal live attenuated vaccine within the 28 days prior to and after Dose 1 study administration
- •Unless given on the day of the first study intervention administration, any other injectable live attenuated vaccines within the 28 days prior to and after. Concomitant receipt on the day of the first study intervention administration is allowed
- •Planned receipt of any monoclonal antibody for RSV (such as Nirsevimab or Palivizumab) for the duration of the study.
- •Previous receipt of an investigational RSV vaccine or receiving any anti-RSV product (such as ribavirin or RSV immune globulin) at the time of enrollment. Previous receipt of an RSV monoclonal antibody within 6 months prior to the first study vaccine administration.
- •Receipt of immune globulins, blood or blood-derived products in the past 3 months
- •Receipt of intranasal and intra-ocular medications within 3 days prior to study enrollment
- •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
- •Note: The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
研究组 & 干预措施
Cohort 1: Group 4-Control
Participants received 2 intranasal administrations of placebo
干预措施: Placebo (Biological)
Cohort 2: Group 4-Control
Participants received 2 intranasal administrations of placebo
干预措施: Placebo (Biological)
Cohort 1: Group 1- (SD RSVt vaccine)
Participants received 2 intranasal administrations of SD RSVt vaccine
干预措施: Standard Dose (SD) RSVt vaccine (Biological)
Cohort 1: Group 2-Control
Participants received 2 intranasal administrations of placebo
干预措施: Placebo (Biological)
Cohort 1: Group 3- (HD RSVt vaccine)
Participants received 2 intranasal administrations of HD RSVt vaccine
干预措施: High Dose (HD) RSVt vaccine (Biological)
Cohort 2: Group 1- (LD RSVt vaccine)
Participants received 2 intranasal administrations of LD RSVt vaccine
干预措施: Low Dose (LD) RSVt vaccine (Biological)
Cohort 2: Group 2- (SD RSVt vaccine)
Participants received 2 intranasal administrations of SD RSVt vaccine
干预措施: Standard Dose (SD) RSVt vaccine (Biological)
Cohort 2: Group 3- (HD RSVt vaccine
Participants received 2 intranasal administrations of HD RSVt vaccine
干预措施: High Dose (HD) RSVt vaccine (Biological)
结局指标
主要结局
Cohort 2: Geometric Mean Titers (GMT) of RSV A Serum Neutralizing Antibodies at Day 85 (Post-Dose 2)
时间窗: Day 85 (28 days post-vaccination 2)
Serum samples were planned to be collected at specified timepoints for immunogenicity assessments. RSV A serum neutralizing antibody titers were planned to be determined using a validated plaque reduction neutralization test (PRNT).
Cohort 2: Geometric Mean Titers of RSV B Serum Neutralizing Antibodies at Day 85 (Post-Dose 2)
时间窗: Day 85 (28 days post-vaccination 2)
Serum samples were planned to be collected at specified timepoints for immunogenicity assessments. RSV B serum neutralizing antibody titers were planned to be determined using a validated PRNT.
Cohorts 1 and 2: Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs)
时间窗: Up to 30 minutes after each vaccination (post-dose on Day 1)
An AE was any untoward medical occurrence in a clinical study participant temporally associated with the use of study vaccine, whether or not considered related to the study vaccine. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, i.e., pre-listed in the case report form (CRF) in terms of diagnosis and onset window post-vaccination. All participants were observed for 30 minutes after each vaccination and any unsolicited AEs that occurred during that time were recorded as immediate unsolicited AEs.
Cohorts 1 and 2: Number of Participants With Solicited Administration Site Reactions
时间窗: Up to 21 days after each vaccination (post-dose on Day 1)
A solicited injection/administration site reactions were adverse reactions (AR) at and around the injection/administration site of the study vaccine observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF and considered as related to the study vaccine administered.
Cohorts 1 and 2: Number of Participants With Solicited Systemic Reactions
时间窗: Up to 21 days after each vaccination (post-dose on Day 1)
A solicited reaction was an expected AR (sign or symptom) observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF and considered as related to the study vaccine administered.
Cohorts 1 and 2: Number of Participants With Unsolicited Adverse Events
时间窗: Up to 28 days after each vaccination (post-dose on Day 1)
An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions, that is, pre-listed in the CRF in terms of diagnosis and onset window post-vaccination.
Cohorts 1 and 2: Number of Participants With Medically Attended Adverse Events (MAAEs)
时间窗: From first dose of study vaccine administration (Day 1) to 198 days
An MAAE was defined as a new onset or a worsening of a condition that prompted the participant or participant's parent/legally acceptable representative to seek unplanned medical advice at a physician's office or emergency department.
Cohorts 1 and 2: Number of Participants With Serious Adverse Events (SAEs)
时间窗: From first dose of study vaccine administration (Day 1) to 198 days
An SAE was defined as any AE that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was other medically important event.
Cohorts 1 and 2: Number of Participants With Adverse Events of Special Interest (AESIs)
时间窗: From first dose of study vaccine administration (Day 1) to 198 days
An AESI (serious or non-serious) was one of scientific and medical concern specific to the sponsor's study vaccine or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor was appropriate. Acute wheeze and anaphylaxis were collected as AESI.
次要结局
- Cohort 1: Geometric Mean Titers of RSV A and B Serum Neutralizing Antibodies at Baseline (Day 1) and Day 85(Baseline (Day 1) and Day 85)
- Cohorts 1 and 2: Mean Titers of RSV Serum Anti-F Immunoglobulin (Ig) A and IgG Antibodies at Baseline (Day 1) and Day 85(Baseline (Day 1) and Day 85)
- Cohorts 1 and 2: Percentage of Participants With Quantified Shedding >=3.37 Lower Limit of Quantitation (LLOQ)(Day 8 and Day 64)
- Cohorts 1 and 2: Percentage of Participants With Detectable Shedding >=2.08 Limit of Detection(Day 8 and Day 64)
- Cohorts 1 and 2: Titer of Vaccine Virus Shedding in Participants Detected in Nasal Samples Quantified by Quantitative Real Time-Polymerase Chain Reaction(Day 8 and Day 64)