Study of a Respiratory Syncytial Virus Candidate Encapsulated in a Lipid Nanoparticle Based Formulation in Adults Aged 18 to 50 Years and 60 Years and Older

Sanofi Pasteur, a Sanofi Company865 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (33)

Optimal Research Alabama Site Number : 8400032

Huntsville, Alabama, United States

Aventiv Research Mesa Site Number : 8400020

Mesa, Arizona, United States

CVS Health - Peoria Site Number : 8400042

Peoria, Arizona, United States

CVS Health - Phoenix Site Number : 8400041

Phoenix, Arizona, United States

Velocity Clinical Research - San Diego - ERN - PPDS Site Number : 8400010

La Mesa, California, United States

Outcomes

Primary Outcomes

Stage 1 (Sentinel and Main Cohort) and Stage 2: Number of Participants With Immediate Unsolicited Systemic Adverse Events (AEs)

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.

Time frame: Up to 30 minutes post-primary vaccination on Day 1

Stage 1 (Sentinel and Main Cohort) and Stage 2: Number of Participants With Solicited Injection Site Reactions and Systemic Reactions

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.

Time frame: From Day 1 (first dose of primary vaccination) up to Day 8 (7 days post-primary vaccination on Day 1)

Stage 1 (Sentinel and Main Cohort) and Stage 2: Number of Participants With Unsolicited Adverse Events

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.

Time frame: From Day 1 (first dose of primary vaccination) up to Day 29 (28 days post-primary vaccination on Day 1)

Stage 1 (Sentinel and Main Cohort): Number of Participants With Medically Attended Adverse Events (MAAEs)

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.

Time frame: From Day 1 (first dose of primary vaccination) up to Day 29 (28 days post-primary vaccination on Day 1)

Stage 2: Number of Participants With Medically Attended Adverse Events

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.

Time frame: From Day 1 (first dose of primary vaccination) to Day 180

Stage 1 (Sentinel and Main Cohort) and Stage 2: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

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.

Time frame: 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)

Stage 1 (Sentinel and Main Cohort) and Stage 2: Number of Participants With Shifts From Baseline to Out-of-Range Biological Test Results

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).

Time frame: From baseline (Day -14 to Day -1) up to Day 8 (7 days post-primary vaccination on Day 1)

Stage 1 (Sentinel and Main Cohort): Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against Respiratory Syncytial Virus A

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.

Time frame: Day 1 (pre-primary vaccination) and Day 29 (28 days post-primary vaccination on Day 1)

Stage 2: Geometric Mean Titers of Neutralizing Antibodies Against Respiratory Syncytial Virus A and Respiratory Syncytial Virus B

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.

Time frame: Day 1 (pre-primary vaccination) and Day 29 (28 days post-primary vaccination on Day 1)

Secondary Outcomes

Stage 1 (Booster Cohort): Number of Participants With Immediate Unsolicited Systemic Adverse Events

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.

Time frame: 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

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.

Time frame: 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

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.

Time frame: 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

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

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.

Time frame: From baseline (Month 12: Day -14 to Day -1) up to 7 days post-booster vaccination at Month 12