A Phase I/IIa, Randomized, Placebo-controlled Multi-arm Dose-finding Study to Evaluate the Safety and Immunogenicity of a RSV Vaccine Candidate in Adult Participants 18 to 50 Years of Age in Phase I, and 60 Years and Older in Phase IIa
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 865
- 试验地点
- 66
- 主要终点
- Presence of unsolicited systemic adverse events (AEs)
研究概览
简要总结
Brief Summary of Stage 1:
The purpose of Stage 1 (Phase I/IIa) was to assess the safety and immunogenicity of a single intramuscular (IM) injection of 3 dose-levels of an Respiratory Syncytial Virus (RSV) vaccine candidate formulated with 2 different lipid nanoparticles (LNPs) in healthy adult participants aged between 18 to 50 years, and 60 years and older. The primary objectives of this stage were to assess the safety and immunogenicity profiles across the dose-level groups (low, medium, and high doses) with 2 LNPs. This stage evaluated the safety and immunogenicity of a booster vaccination administered 12 months after the primary vaccination in a subset of the study population.
Brief Summary of Stage 2:
The study also incorporated a Stage 2 (Phase IIa, dose-ranging design) that included adults aged 60 years and older to assess the safety and immunogenicity of different doses of RSV vaccine encapsulated in one of the LNPs. In the Phase IIa dose-ranging stage, eligible participants were randomly assigned in a 1:1:1 ratio to receive a single IM administration of RSV vaccine candidate doses, or placebo. Multiple safety analyses were performed, minimally at D07 and D28.
详细描述
Stage 1:
The duration of each participant's participation was 12 months for the Sentinel and Main Cohorts, 24 months overall for the subset of participants enrolled in the Booster Cohort.
Treatment Duration:
- Sentinel Cohort: 1 intra-muscular (IM) injection. Participants were followed for 12 months post-vaccination.
- Main Cohort: 1 IM injection. Participants were followed for 12 months post-vaccination.
- Booster Cohort: 1 IM injection 12 months after the primary vaccination. Participants were followed for 12 months after administration of the booster dose.
Stage 2:
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
Sentinel Cohort: single-blind
- Investigators, study staff who conduct the safety assessment, and the participant will not know which study intervention is administered
- Sponsor study staff and study staff preparing/administering the study interventions and not involved with the safety evaluation will know which study intervention is administered Main and Booster Cohorts in Stage 1 and Stage 2: Modified double-blind
- Investigators, study staff who conduct the safety assessment, and the participant will not know which study intervention is administered
- Only the study staff who prepare and administer the study intervention and are not involved with the safety evaluation will know which study intervention is administered
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Sentinel Cohort Stage 1: Aged 18 to 50 years on the day of inclusion
- •Main Cohort Stage 1 and Stage 2: Aged 60 years or older on the day of inclusion
- •Stage 1 and Stage 2:
- •Sentinel Cohort: A female participant was eligible to participate if she was not pregnant or breastfeeding and:
- •Was of non-childbearing potential. To be considered of non-childbearing potential, a female must have been postmenopausal for at least 1 year or surgically sterile OR
- •Was of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to study intervention administration until at least 12 weeks after study intervention administration.
- •Main and Booster Cohorts: A female participant was eligible to participate if she was not pregnant or breastfeeding and:
- •Was of non-childbearing potential. To be considered of non-childbearing potential, a female must have been postmenopausal for at least 1 year or surgically sterile.
- •Able to attend all scheduled visits and to comply with all study procedures
- •Informed consent form was been signed and dated
排除标准
- •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 (eg, polyethylene glycol, polysorbate); history of a life-threatening reaction to the study interventions used in the study or to a product containing any of the same substances; any allergic reaction (eg, anaphylaxis) after administration of mRNA COVID-19 vaccine
- •History of RSV-associated illness, diagnosed clinically, serologically, or microbiologically in the last 12 months
- •Previous history of myocarditis, pericarditis, and/or myopericarditis
- •Thrombocytopenia or bleeding disorder, contraindicating IM injection based on investigator's judgment
- •Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular injection
- •Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with study conduct or completion
- •Alcohol, prescription drug, or substance abuse that, in the opinion of the investigator, might interfere with the study conduct or completion
- •Receipt of immune globulins, blood, or blood-derived products in the past 3 months
- •Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw
- •Participation at the time of study enrollment (or in the 4 weeks preceding the first study intervention administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
- •Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
- •Self-reported or documented human immunodeficiency virus (HIV) detected by any FDA-approved/validated test, hepatitis B virus surface antigen (HBsAg), hepatits B core antibodies (HBcAb), or hepatitis C virus antibodies (HCV Abs), or positive SARS-CoV-2 RT-PCR or antigen test
- •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
- •The above information was not intended to contain all considerations relevant to a potential participation in a clinical trial.
研究组 & 干预措施
Stage 1: Sentinel Cohort: RSV Vaccine Dose A1
Participants enrolled in the Sentinel Cohort received 0.5 mL RSV vaccine dose A1 as an IM injection on Day 1 of Stage 1.
干预措施: RSV vaccine candidate (Biological)
Stage 1: Sentinel Cohort: RSV Vaccine Dose A2
Participants enrolled in the Sentinel Cohort received 0.5 mL RSV vaccine dose A2 as an IM injection on Day 1 of Stage 1.
干预措施: RSV vaccine candidate (Biological)
Stage 1: Sentinel Cohort: RSV Vaccine Dose B1
Participants enrolled in the Sentinel Cohort received 0.5 mL RSV vaccine dose B1 as an IM injection on Day 1 of Stage 1.
干预措施: RSV vaccine candidate (Biological)
Stage 1: Sentinel Cohort: RSV Vaccine Dose B2
Participants enrolled in the Sentinel Cohort received 0.5 mL RSV vaccine dose B2 as an IM injection on Day 1 of Stage 1.
干预措施: RSV vaccine candidate (Biological)
Stage 1: Sentinel Cohort: RSV Vaccine Dose C1
Participants enrolled in the Sentinel Cohort received 0.5 mL RSV vaccine dose C1 as an IM injection on Day 1 of Stage 1.
干预措施: RSV vaccine candidate (Biological)
Stage 1: Sentinel Cohort: RSV Vaccine Dose C2
Participants enrolled in the Sentinel Cohort received 0.5 mL RSV vaccine dose C2 as an IM injection on Day 1 of Stage 1.
干预措施: RSV vaccine candidate (Biological)
Stage 1: Sentinel Cohort: Placebo
Participants enrolled in the Sentinel Cohort received 0.5 mL placebo matched to RSV vaccine as an IM injection on Day 1 of Stage 1.
干预措施: Placebo (Other)
Stage 1: Main Cohort: RSV Vaccine Dose A1
Participants enrolled in the Main Cohort received 0.5 mL RSV vaccine dose A1 as an IM injection on Day 1 of Stage 1.
干预措施: RSV vaccine candidate (Biological)
Stage 1: Main Cohort: RSV Vaccine Dose A2
Participants enrolled in the Main Cohort received 0.5 mL RSV vaccine dose A2 as an IM injection on Day 1 of Stage 1.
干预措施: RSV vaccine candidate (Biological)
Stage 1: Main Cohort: RSV Vaccine Dose B1
Participants enrolled in the Main Cohort received 0.5 mL RSV vaccine dose B1 as an IM injection on Day 1 of Stage 1.
干预措施: RSV vaccine candidate (Biological)
Stage 1: Main Cohort: RSV Vaccine Dose B2
Participants enrolled in the Main Cohort received 0.5 mL RSV vaccine dose B2 as an IM injection on Day 1 of Stage 1.
干预措施: RSV vaccine candidate (Biological)
Stage 1: Main Cohort: RSV Vaccine Dose C1
Participants enrolled in the Main Cohort received 0.5 mL RSV vaccine dose C1 as an IM injection on Day 1 of Stage 1.
干预措施: RSV vaccine candidate (Biological)
Stage 1: Main Cohort: RSV Vaccine Dose C2
Participants enrolled in the Main Cohort received 0.5 mL RSV vaccine dose C2 as an IM injection on Day 1 of Stage 1.
干预措施: RSV vaccine candidate (Biological)
Stage 1: Main Cohort: Placebo
Participants enrolled in the Main Cohort received 0.5 mL placebo matched to RSV vaccine as an IM injection on Day 1 of Stage 1.
干预措施: Placebo (Other)
Stage 2: RSV Vaccine Dose C2
Participants received 0.5 mL RSV vaccine dose C2 as an IM injection on Day 1 of Stage 2.
干预措施: RSV vaccine candidate (Biological)
Stage 2: RSV Vaccine Dose D
Participants received 0.5 mL RSV vaccine dose D as an IM injection on Day 1 of Stage 2.
干预措施: RSV vaccine candidate (Biological)
Stage 2: Placebo
Participants received 0.5 mL placebo matched to RSV vaccine as an IM injection on Day 1 of Stage 2.
干预措施: Placebo (Other)
结局指标
主要结局
Presence of unsolicited systemic adverse events (AEs)
时间窗: Within 30 minutes after vaccination
Number of participants experienciing unsolicited systemic adverse events
Presence of solicited injection site or systemic reactions
时间窗: Within 7 days after vaccination
Number of participants reporting: * injection site reactions: pain, erythema and swelling * systemic reactions: fever, headache, malaise, myalgia, arthralgia and chills
Presence of unsolicited AEs
时间窗: Within 28 days after vaccination
Number of participants experiencing unsolicited AEs
Presence of medically attended adverse events (MAAEs)
时间窗: Within 28 days after vaccination
Number of participants experiencing MAAEs
Presence of serious adverse events (SAEs)
时间窗: Month 12
Number of participants experiencing SAEs
Presence of adverse events of special interest (AESIs)
时间窗: Month 12
Number of participants experiencing AESIs
Presence of out-of-range biological test results
时间窗: Within 7 days after vaccination
Number of participants with biological safety assessment values out of normal range (as per the laboratory performing the test)
Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers pre-vaccination at Day 1
时间窗: Day 1
Nab titers pre-vaccination
Geometric Mean Titers (GMTs) of neutralizing antibody (nAb) titers post-primary vaccination at Day 29
时间窗: Day 29
Nab titers post-vaccination
Stage 1 (Sentinel and Main Cohort) and Stage 2: Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs)
时间窗: Up to 30 minutes post-primary vaccination 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. Immediate events were recorded to capture medically relevant unsolicited systemic AEs which occurred within the first 30 minutes after vaccination. 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.
Stage 1 (Sentinel and Main Cohort) and Stage 2: Number of Participants With Solicited Injection Site Reactions and Systemic Reactions
时间窗: From Day 1 (first dose of primary vaccination) up to Day 8 (7 days post-primary vaccination on Day 1)
An injection site reaction was an adverse reaction (AR) at and around the injection site of the study vaccine. Injection site reactions were commonly inflammatory reactions. Solicited injection site reactions were reactions at and around the injection site of the study vaccine observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF. Solicited systemic reactions were systemic AEs observed and reported under the conditions (nature and onset) pre-listed in the protocol and CRF. Solicited reactions were considered to be related to the study vaccine administered.
Stage 1 (Sentinel and Main Cohort) and Stage 2: Number of Participants With Unsolicited Adverse Events
时间窗: From Day 1 (first dose of primary vaccination) up to Day 29 (28 days post-primary vaccination 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 CRF in terms of diagnosis and onset window post-vaccination.
Stage 1 (Sentinel and Main Cohort): Number of Participants With Medically Attended Adverse Events (MAAEs)
时间窗: From Day 1 (first dose of primary vaccination) up to Day 29 (28 days post-primary vaccination on Day 1)
An MAAE was a new-onset or a worsening of a condition that prompted the participant to seek unplanned medical advice at a physician's office or Emergency Department.
Stage 2: Number of Participants With Medically Attended Adverse Events
时间窗: From Day 1 (first dose of primary vaccination) to Day 180
An MAAE was a new-onset or a worsening of a condition that prompted the participant to seek unplanned medical advice at a physician's office or Emergency Department.
Stage 1 (Sentinel and Main Cohort) and Stage 2: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
时间窗: From Day 1 (first dose of primary vaccination) to Day 365 (Stage 1 Sentinel and Main Cohorts); From Day 1 (first dose of primary vaccination) to Day 180 (Stage 2)
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 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 an important medical event. An AESI (serious or non-serious) was 1 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.
Stage 1 (Sentinel and Main Cohort) and Stage 2: Number of Participants With Shifts From Baseline to Out-of-Range Biological Test Results
时间窗: From baseline (Day -14 to Day -1) up to Day 8 (7 days post-primary vaccination on Day 1)
Clinical evaluation of laboratory parameters (hematology, clinical chemistry and coagulation parameters) was performed to determine out-of-range values (below or above normal range). Number of participants with a shift from baseline to out-of-range value within 7 days after primary vaccination (Day 8) are reported. Laboratory parameters with a notable shift from baseline included: hematology: hemoglobin, white blood cells (WBC), red blood cells (RBC); clinical chemistry: blood urea nitrogen (BUN), potassium, glucose, C-reactive protein (CRP), direct bilirubin, troponin I; and coagulation parameters: partial thromboplastin time (PTT).
Stage 1 (Sentinel and Main Cohort): Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against Respiratory Syncytial Virus A
时间窗: Day 1 (pre-primary vaccination) and Day 29 (28 days post-primary vaccination on Day 1)
Neutralizing antibodies activity against RSV A was measured using the RSV plaque reduction neutralization test (PRNT) (micro-PRNT). RSV A serum neutralizing antibodies titers were expressed as 1/dilution.
Stage 2: Geometric Mean Titers of Neutralizing Antibodies Against Respiratory Syncytial Virus A and Respiratory Syncytial Virus B
时间窗: Day 1 (pre-primary vaccination) and Day 29 (28 days post-primary vaccination on Day 1)
Neutralizing antibodies activity against RSV A and RSV B was measured using the RSV PRNT (micro-PRNT). RSV A and RSV B serum neutralizing antibodies titers were expressed as 1/dilution.
次要结局
- Presence of immediate unsolicited systemic AEs (Stage 1)(Within 30 minutes after vaccination)
- Presence of solicited injection site or systemic reactions post-booster vaccination (Stage 1)(Within 7 days after vaccination)
- Presence of unsolicited AEs post-booster vaccination (Stage 1)(Within 28 days after vaccination)
- Presence of MAAEs (Stage 1)(Within 28 days after vaccination)
- Presence of serious adverse events (SAEs) post-booster vaccination (Stage 1)(Throughout the booster study, approximately 12 months)
- Presence of adverse events of special interest post-booster vaccination (Stage 1)(Throughout the booster study, approximately 12 months)
- Presence of out-of-range biological test results post-booster vaccination (Stage 1)(Within 7 days after vaccination)
- RSV-A serum nAb titers at pre-vaccination (D01) and 28 days post- primary vaccination (D29) (Stage 1)(Day 1, Day 29, Month 3, Month 6 and Month 12)
- GMTs of serum anti-F immunoglobulin G (IgG) antibody (Ab) titers post-primary vaccination (Stage 1)(Day 1, Day 29, Month 3, Month 6 and Month 12)
- GMTs of serum anti-F IgG Ab titers pre-vaccination (Stage 2)(Day 1)
- GMTs of serum anti-F IgG Ab titers post-vaccination (Stage 2)(Day 29)
- GMTs of serum anti-F IgG Ab titers post-booster vaccination (Stage 1)(Day 1, Day 29, Month 3, Month 6 and Month 12 post-booster)
- GMTs of RSV-A serum nAb post-booster vaccination (Stage 1)(Day 1, Day 29, Month 3, Month 6 and Month 12 post-booster)
- Stage 1 (Booster Cohort): Number of Participants With Immediate Unsolicited Systemic Adverse Events(Up to 30 minutes post-booster vaccination at Month 12)
- Stage 1 (Booster Cohort): Number of Participants With Solicited Injection Site Reactions and Systemic Reactions(Up to 7 days post-booster vaccination at Month 12)
- Stage 1 (Booster Cohort): Number of Participants With Unsolicited Adverse Events and Medically Attended Adverse Events(Up to 28 days post-booster vaccination at Month 12)
- Stage 1 (Booster Cohort): Number of Participants With Serious Adverse Events and Adverse Events of Special Interest(From Month 12 (first dose of booster vaccination) to Month 24)
- Stage 1 (Booster Cohort): Number of Participants With Shifts From Baseline to Out-of-Range Biological Test Results(From baseline (Month 12: Day -14 to Day -1) up to 7 days post-booster vaccination at Month 12)
- Stage 1 (Sentinel and Main Cohort): Geometric Mean Titers of Neutralizing Antibodies Against Respiratory Syncytial Virus A(3, 6, and 12 months post-primary vaccination on Day 1)
- Stage 1 (Sentinel and Main Cohort): Geometric Mean Concentration of Binding Antibodies Against Respiratory Syncytial Virus Anti-F Immunoglobulin G (IgG)(Day 1 (pre-primary vaccination), Day 29, and 3, 6, and 12 months post-primary vaccination on Day 1)
- Stage 1 (Booster Cohort): Geometric Mean Titers of Neutralizing Antibodies Against Respiratory Syncytial Virus A(Month 12 (pre-booster vaccination), and 28 days (Month 13), 3 months (Month 15), 6 months (Month 18), and 12 months (Month 24) post-booster vaccination at Month 12)
- Stage 1 (Booster Cohort): Geometric Mean Concentration of Binding Antibodies Against Respiratory Syncytial Virus Anti-F Immunoglobulin G(Month 12 (pre-booster vaccination), and 28 days (Month 13), 3 months (Month 15), 6 months (Month 18), and 12 months (Month 24) post-booster vaccination on Month 12)
- Stage 2: Geometric Mean Concentration of Binding Antibodies Against Respiratory Syncytial Virus Anti-F Immunoglobulin G(Day 1 (pre-primary vaccination) and Day 29 (28 days post-primary vaccination on Day 1))