Respiratory Syncytial Virus Immunization
Conditions
Brief summary
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.
Detailed description
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: The duration of each participant's participation was approximately 6 months. Treatment Duration: 1 IM injection. Participants were followed for approximately 6 months post vaccination
Interventions
BIOLOGICALRSV vaccine candidate
Pharmaceutical Form: Liquid frozen solution in a vial Route of Administration: Intramuscular injection
OTHERPlacebo
Pharmaceutical Form: Liquid Route of Administration: Intramuscular injection
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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
Intervention model description
Sequential (Phase I)/ parallel (Phase IIa)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1 (Sentinel and Main Cohort) and Stage 2: Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs) | 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 | 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 | 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) | 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 | 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) | 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 | 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 | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1 (Booster Cohort): Number of Participants With Immediate Unsolicited Systemic Adverse Events | Up to 30 minutes post-booster vaccination at Month 12 | 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 CRF in terms of diagnosis and onset window post-vaccination. |
| 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 | An injection site reaction was an 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 (Booster Cohort): Number of Participants With Unsolicited Adverse Events and Medically Attended Adverse Events | Up to 28 days post-booster vaccination at Month 12 | 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. 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 (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 | 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 (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 | Clinical evaluation of laboratory parameters (hematology and clinical chemistry) 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 booster vaccination (Month 12 + 7 days) are reported. Laboratory parameters with a notable shift from baseline included: hematology: RBC; clinical chemistry: potassium, glucose, direct bilirubin. |
| 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 | Neutralizing antibodies activity against RSV A was measured using the RSV PRNT (micro-PRNT). RSV A serum neutralizing antibodies titers were expressed as 1/dilution. |
| 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 | Binding antibodies activity against RSV anti-F IgG was measured using enzyme-linked immunosorbent assay (ELISA). Geometric mean concentrations were expressed as endotoxin units per milliliter (EU/mL). |
| 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 | Neutralizing antibodies activity against RSV A was measured using the RSV PRNT (micro-PRNT). RSV A serum neutralizing antibodies titers were expressed as 1/dilution. |
| 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 | Binding antibodies activity against RSV anti-F IgG was measured using ELISA. Geometric mean concentrations were expressed as EU/mL. |
| 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) | Binding antibodies activity against RSV anti-F IgG was measured using ECL assay. Geometric mean concentrations were expressed as arbitrary units (AU)/mL. |
Countries
Australia, Puerto Rico, United States
Contacts
STUDY_DIRECTORClinical Sciences & Operations
Sanofi
Participant flow
Recruitment details
This study was conducted at 28 centers in 3 countries between 17 November 2022 to 02 May 2025. 790 participants were enrolled in Stage 1 (Sentinel and Main Cohort) and 75 participants were enrolled in Stage 2.
Pre-assignment details
A total of 865 unique participants were enrolled in the study. 129 eligible participants from the Stage 1: Main Cohort were included in the Stage 1: Booster Cohort because these assessed separate objectives. Dose groups are defined by combinations of dose level (A to D) and formulation type, with dose levels increasing from A (lowest) to D (highest) in each Stage.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 41.4 years STANDARD_DEVIATION 9.07 |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants |
| Race (NIH/OMB) Asian | 15 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 10 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 700 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 30 | 0 / 100 | 0 / 101 | 1 / 100 | 0 / 100 | 0 / 100 | 0 / 98 | 1 / 99 | 1 / 31 | 0 / 31 | 0 / 33 | 0 / 34 | 0 / 25 | 0 / 24 | 0 / 26 |
| other Total, other adverse events | 5 / 10 | 2 / 9 | 5 / 10 | 6 / 10 | 8 / 10 | 8 / 10 | 8 / 30 | 54 / 100 | 47 / 101 | 72 / 100 | 74 / 100 | 76 / 100 | 63 / 98 | 38 / 99 | 24 / 31 | 9 / 31 | 27 / 33 | 12 / 34 | 19 / 25 | 22 / 24 | 10 / 26 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 | 0 / 10 | 0 / 10 | 1 / 10 | 0 / 10 | 0 / 30 | 10 / 100 | 4 / 101 | 8 / 100 | 6 / 100 | 3 / 100 | 7 / 98 | 8 / 99 | 3 / 31 | 3 / 31 | 1 / 33 | 1 / 34 | 0 / 25 | 0 / 24 | 1 / 26 |
Outcome results
None listed