Study of an Live-Attenuated Respiratory Syncytial Virus Vaccine in Infants and Toddlers

Study Overview
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Brief Summary
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The primary objectives of the study are: To assess the safety profile of each dose of the study product after each and any administration in all infants and toddlers regardless of baseline serostatus. To characterize the Respiratory Syncytial Virus (RSV) A serum neutralizing antibody responses to the study product in each vaccine group after vaccination in RSV-naïve participants. The secondary objectives of the study are: To quantify the amount of vaccine virus shed by each participant by baseline serostatus. To determine the proportion of vaccinated infants and toddlers in each vaccine group infected with the vaccine virus at D56 (56 days after vaccination 1) for Cohorts 1, 2, 3 and 4, and at Day 84 (28 days after vaccination 2) for Cohorts 2 and 4 by baseline serostatus. To characterize the RSV A serum neutralizing antibody responses to the study product in each vaccine group after vaccination in RSV-experienced participants. To characterize serum RSV anti-F immunoglobulin G (IgG) antibody responses to the study product in each vaccine group after vaccination by baseline serostatus. To characterize serum RSV antibody responses (RSV A-neutralizing and anti-RSV F IgG) to the study product in each vaccine group after the RSV surveillance season or at least 5 months after the last vaccine administration by baseline serostatus.

Detailed Description
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Study duration per participant is maximum 12 months

Official Title
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Safety, Immunogenicity, Infectivity, and Dose-Finding Study of an Investigational Live-Attenuated Respiratory Syncytial Virus (RSV) Vaccine in Infants and Toddlers

Conditions
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Respiratory Syncytial Virus Infection

Intervention / Treatment
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* Biological: RSV vaccine formulation 1
* Biological: RSV vaccine formulation 2
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria : Aged 6 through 18 months at Day 0. Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative (and by independent witness if required by local regulations). Participant and parent / guardian / legally acceptable representative are able to attend all scheduled visits and to comply with all trial procedures Exclusion Criteria: Born at less than 34 weeks gestation Born at less than 37 weeks gestation and less than 1 year of age at the time 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). Probable or confirmed case of Coronavirus Disease 2019 (COVID-19). Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances Any chronic illness • Chronic illness may include, but is not limited to, cardiac disorders, lung disease (including any history of reactive airway disease, receipt of bronchodilator therapy, or medically diagnosed wheezing), renal disorders, auto-immune disorders, diabetes, psychomotor diseases, and known congenital or genetic diseases Any history of medically diagnosed wheezing Any acute febrile, respiratory or gastrointestinal illness in the past 24 hours that according to investigator judgment is significant enough to interfere with successful inoculation on the day of vaccination. ebrile event has subsided Any previous anaphylactic reaction Current suspected or documented developmental disorder, delay, or other developmental problem Receipt of any of the following vaccines prior to enrollment: any influenza vaccine within 7 days prior, or 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 Previous receipt of a licensed or investigational RSV vaccine or previous receipt or planned administration of any anti-RSV product (such as ribavirin or RSV immune immune globulins [IG] or RSV monoclonal antibody) Receipt of immune globulins, blood or blood-derived products in the past 6 months prior to enrolment Receipt of any of the following medications within 3 days prior to study enrollment (Day 0): systemic antibacterial, antiviral, antifungal, anti-parasitic, or antituberculous agents, whether for treatment or prophylaxis, or intranasal medications, or other prescription medication except as permitted concomitant medications (prescription or non-prescription) including nutritional supplements, medications for gastroesophageal reflux, eye drops, and topical medications, including (but not limited to) cutaneous (topical) steroids, topical antibiotics, and topical antifungal agents Receipt of salicylate (aspirin) or salicylate-containing products within the 28 days prior to enrollment (Day 0) Any previous vaccine-associated adverse reaction that was Grade 3 or above. Note: if grading is not possible, determine if the reaction was considered severe or life threatening; if so, it is exclusionary. Scheduled administration of the following after planned inoculation: any influenza vaccine within 7 days after, or inactivated vaccine or live-attenuated rotavirus vaccine within the 14 days after, or any live vaccine other than rotavirus in the 28 days after, or another investigational vaccine or investigational drug in the 56 days after. Any previous receipt of supplemental oxygen therapy in a home or hospital setting, except the temporary receipt of supplemental oxygen for transient tachypnea in newborn 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 enrollment a person receiving immunosuppressant agents a person living with a solid organ or bone marrow transplant Participation at the time of study enrollment (or in the 6 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure Member of a household that contains, or will contain, an infant who is less than 6 months of age at the enrollment date (or in the 6 weeks preceding the first trial vaccination) through Day 28 Member of a household that contains another child/other children who is/are, or is/are scheduled to be, enrolled in this study in the same year AND the date of enrollment will not be concurrent with the other participant(s) living in the household (i.e., all eligible children from the same household must be enrolled on the same date) Attends a daycare facility and shares a daycare room with infants less than 6 months of age, and parent/guardian is unable or unwilling to suspend daycare for 28 days following inoculation Deprived of freedom in an emergency setting or hospitalized involuntarily Identified as a natural or adopted child of the Investigator or employee with direct involvement in the proposed study The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 18 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (RSV vaccine formulation 1)<br>1 administration of RSV vaccine formulation 1 on Day 0 | Biological: RSV vaccine formulation 1<br>* Pharmaceutical form: Suspension of virus Route of administration: Intranasal<br>|
| Placebo Comparator: Cohort 1 (Placebo)<br>1 administration of placebo on Day 0 | Biological: Placebo<br>* Pharmaceutical form: Suspension Route of administration: Intranasal<br>|
| Experimental: Cohort 2 (RSV vaccine formulation 1)<br>2 administrations of RSV vaccine formulation 1 on Day 0 and Day 56 | Biological: RSV vaccine formulation 1<br>* Pharmaceutical form: Suspension of virus Route of administration: Intranasal<br>|
| Placebo Comparator: Cohort 2 (Placebo)<br>2 administrations of placebo on Day 0 and Day 56 | Biological: Placebo<br>* Pharmaceutical form: Suspension Route of administration: Intranasal<br>|
| Experimental: Cohort 3 (RSV vaccine formulation 2)<br>1 administration of RSV vaccine formulation 2 on Day 0 | Biological: RSV vaccine formulation 2<br>* Pharmaceutical form: Suspension of virus Route of administration: Intranasal<br>|
| Placebo Comparator: Cohort 3 (Placebo)<br>1 administration of placebo on Day 0 | Biological: Placebo<br>* Pharmaceutical form: Suspension Route of administration: Intranasal<br>|
| Experimental: Cohort 4 (RSV vaccine formulation 1)<br>2 administrations of RSV vaccine formulation 1 on Day 0 and Day 56 | Biological: RSV vaccine formulation 1<br>* Pharmaceutical form: Suspension of virus Route of administration: Intranasal<br>|
| Experimental: Cohort 4 (RSV vaccine formulation 2)<br>2 administrations of RSV vaccine formulation 2 on Day 0 and Day 56 | Biological: RSV vaccine formulation 2<br>* Pharmaceutical form: Suspension of virus Route of administration: Intranasal<br>|
| Placebo Comparator: Cohort 4 (Placebo)<br>2 administrations of placebo on Day 0 and Day 56 | Biological: Placebo<br>* Pharmaceutical form: Suspension Route of administration: Intranasal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants reporting immediate adverse events | Immediate adverse events are unsolicited systemic adverse events reported in the 30 minutes after vaccination. | Within 30 minutes after vaccination | 
| Number of participants reporting solicited reactions | Solicited administrative site reaction: rhinorrhea. Solicited systemic reactions: fever, vomiting, crying abnormal, drowsiness, appetite lost, and irritability. | Within 28 days after vaccination | 
| Number of participants reporting unsolicited adverse events | Unsolicited adverse events are spontaneously reported adverse events. | Within 28 days after vaccination | 
| Number of participants reporting adverse events of special interest | Adverse events of special interest pre-defined adverse event collected using the same process as for other adverse events. | Within 28 days after vaccination | 
| Number of participants reporting medically attended adverse events | Medically attended adverse events are adverse events with a new onset or a worsening of a condition that prompts the participant or participant's parent/guardian to seek unplanned medical advice at a physician's office or Emergency Department. | Within 28 days after vaccination | 
| Number of participants reporting serious adverse events | Serious adverse events are collected throughout the study, from Day 0 until the end of the study. | Day 0 to maximum Month 12 | 
| RSV A serum neutralizing antibody levels after first vaccine administration | RSV A serum neutralizing antibody levels assessed in RSV-naïve participants in Cohorts 1, 2, 3, and 4. | Day 56 | 
| RSV A serum neutralizing antibody levels after second vaccine administration | RSV A serum neutralizing antibody levels are assessed in RS-naïve participants in Cohorts 2 and 4. | Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titer of vaccine virus shedding (polymerase chain reaction [RT-PCR]) | Titers are assessed by PCR at Day 7 for Cohorts 1, 2, 3 and 4 and Day 63 for Cohorts 2 and 4. | 7 days after vaccination | 
| Number of participants infected with the vaccine virus | Infection is defined as detection of vaccine in nasal wash by culture or PCR and / or a ≥ 4-fold rise in serum neutralizing antibodies or in serum antibodies to RSV F. Infectivity is assessed on Day 56 for Cohorts 1, 2, 3 and 4, and after vaccination 2 (Day 84) for Cohorts 2 and 4 | Day 56 and Day 84 | 
| RSV A serum neutralizing antibody levels | RSV serum neutralizing antibody levels assessed in RSV-experienced participants on Day 56 for Cohorts 1, 2, 3 and 4, and after vaccination 2 (Day 84) for Cohorts 2 and 4. | Day 56 and Day 84 | 
| RSV serum anti-F binding antibody levels | RSV serum anti-F binding antibody levels assessed on Day 56 for Cohorts 1, 2, 3 and 4, and after vaccination 2 (Day 84) for Cohorts 2 and 4. | Day 56 and Day 84 | 
| RSV A serum neutralizing and serum anti-RSV F IgG antibody titers after the RSV surveillance season or at least 5 months after the last vaccine administration | RSV A serum neutralizing and serum anti-RSV F IgG antibody titers are assessed after the end of the RSV season (on average end of March in the Northern Hemisphere and end of September in the Southern Hemisphere) or at least 5 months after the last vaccine administration. | Within 1 month after the end of the RSV season or at least 5 months after the last vaccine administration. |