A Study to Evaluate the Safety, Tolerability and Immunogenicity of an Investigational RSV Vaccine Candidate (Ad26.RSV.preF) in Adults 18 to 50 Years of Age, and RSV-seropositive Toddlers 12 to 24 Months of Age

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of an intramuscular regimen of two doses (1*10^11 viral particles [vp]) of an investigational respiratory syncytial virus (RSV) vaccine candidate (adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation stabilized F protein [pre-F] [Ad26.RSV.preF]) in adults aged 18 to 50 years and RSV-seropositive toddlers aged 12 to 24 months.

Detailed Description
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The study, designed to assess the safety and tolerability of two doses given one month apart of Ad26.RSV.preF, an investigational RSV vaccine candidate based on a Ad26 vector expressing the RSV F protein, will be conducted in a double blinded manner. The study will be divided in two sequential cohorts: cohort 0 (18-50 year-old adults) and cohort 1 (12-24 month-old RSV seropositive toddlers). The vaccine safety will be monitored by reporting solicited and unsolicited adverse events (AEs) and all serious adverse events (SAEs). The data will be reviewed by an independent data monitoring committee (IDMC) to assess safety data and to ensure the continuing safety of the participants enrolled in this study. The safety will be monitored throughout the study.

Official Title
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A Randomized, Double-blind, Phase 1/2a Study to Evaluate the Safety, Tolerability and Immunogenicity of Ad26.RSV.preF in Adults 18 to 50 Years of Age, RSV-seropositive Toddlers 12 to 24 Months of Age

Conditions
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Respiratory Syncytial Viruses, Respiratory Tract Infections

Intervention / Treatment
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* Biological: Ad26.RSV.preF (1*10^11 vp)
* Biological: Ad26.RSV.preF (5*10^10 vp)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults Participants: Participant must be in good health, without significant medical illness, on the basis of physical examination, medical history, and vital signs measurement Participant must be healthy on the basis of clinical laboratory tests performed at screening. If the results of the laboratory screening tests are outside the local laboratory normal reference ranges and additionally within the limits of toxicity Grade 1 according to the United stated (US) Food and Drug Administration (FDA) toxicity tables, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant and appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator All women of childbearing potential must have a negative highly sensitive serum beta-human chorionic gonadotropin (Beta-hCG) pregnancy test at screening and a negative urine Beta-hCG pregnancy test immediately prior to each study vaccine administration Pediatric Participants: Participant is the product of a normal term pregnancy greater than and equal to (>=) 37 weeks, with a minimum birth weight of 2.5 kilogram (kg) Participants must be in good health without any significant medical illness on the basis of physical examination, medical history, and vital signs performed at screening Exclusion Criteria: Adults Participants: Participant has acute illness (this does not include minor illnesses such as diarrhea) or temperature >=38.0 ºC (degree celsius)/100.4 °F (fahrenheit) within 24 hours prior to the first dose of study vaccine Participant has a history of an underlying clinically significant acute or chronic medical condition or physical examination findings for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments Participant has history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence) Pediatric Participants: Participant's weight is below 10th percentile according to World Health Organization (WHO) pediatric growth and weight charts Participant has any clinically significant acute or chronic medical condition that, in the opinion of the investigator, would preclude participation: example, history of seizure disorders, bleeding/clotting disorder, autoimmune disease, active malignancy, systemic infections, congenital heart disease, history of any pulmonary condition requiring medication, atopy, reactive airway disease, medically-confirmed wheezing, bronchoconstriction or treatment with a beta2 agonist, cystic fibrosis, bronchopulmonary dysplasia, chronic pulmonary disease, medically-confirmed apnea, hospitalization for respiratory illness, or mechanical ventilation for respiratory illness

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 50 Years

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 0: Adults (Ad26.RSV.preF)<br>Participants aged greater than or equal to (>=) 18 to lesser than or equal to (<=) 50 years will receive vector Ad26.RSV.preF at 1*10^11 viral particles (vp) via intramuscular (IM) route (Group 1) on Day 1 and 29. | Biological: Ad26.RSV.preF (1*10^11 vp)<br>* Participants will receive two doses of 0.5 milliliter (mL) (1*10^11 vp) via IM route on Day 1 and 29 of Ad26.RSV.preF.<br>* Other names: JNJ-64400141;|
| Placebo Comparator: Cohort 0: Adults (Placebo)<br>Participants aged >= 18 to <= 50 years will receive placebo via IM route (Group 2) on Day 1 and 29. | Drug: Placebo<br>* Participants will receive either 0.5 mL (cohort 0) or 0.25 mL (cohort 1) of placebo via IM route on Day 1 and 29.<br>|
| Experimental: Cohort 1: RSV seropositive Toddlers (Ad26.RSV.preF)<br>RSV seropositive participants aged >=12 to <=24 months will receive Ad26.RSV.preF at 5*10^10 vp via IM route (Group 3) on Day 1 and 29. | Biological: Ad26.RSV.preF (5*10^10 vp)<br>* RSV seropositive participants will receive two doses of 0.25 mL (5*10^10 vp) via IM route on Day 1 and 29 of Ad26.RSV.preF.<br>* Other names: JNJ-64400141;|
| Placebo Comparator: Cohort 1: RSV seropositive Toddlers (Placebo)<br>RSV seropositive participants aged >= 12 to <= 24 months will receive placebo via IM route (Group 4) on Day 1 and 29. | Drug: Placebo<br>* Participants will receive either 0.5 mL (cohort 0) or 0.25 mL (cohort 1) of placebo via IM route on Day 1 and 29.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Solicited Local Adverse Events (AEs) for 7 Days After First Vaccination | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with study vaccine. Solicited local AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included erythema, swelling/induration, and pain/tenderness. | For 7 days after first vaccination on Day 1 (Up to Day 7) | 
| Number of Participants With Solicited Local Adverse Events (AEs) for 7 Days After Second Vaccination | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with study vaccine. Solicited local AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included erythema, swelling/induration, and pain/tenderness. | For 7 days after second vaccination on Day 29 (Up to Day 35) | 
| Number of Participants With Solicited Systemic Adverse Events for 7 Days After First Vaccination | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with study vaccine. Solicited systemic AEs included were for adult participants: fatigue, headache, myalgia, arthralgia, chills, nausea and fever (defined as body temperature >=38 degree celsius [°C]; for pediatric participants: loss of appetite, vomiting, diarrhea, decreased activity/lethargy, irritability/crying and fever (i.e., body temperature >=38 °C). | For 7 days after first vaccination on Day 1 (Up to Day 7) | 
| Number of Participants With Solicited Systemic Adverse Events for 7 Days After Second Vaccination | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with study vaccine. Solicited systemic AEs included were for adult participants: fatigue, headache, myalgia, arthralgia, chills, nausea and fever (defined as body temperature >=38 degree celsius [°C]; for pediatric participants: loss of appetite, vomiting, diarrhea, decreased activity/lethargy, irritability/crying and fever (i.e., body temperature >=38 °C). | For 7 days after second vaccination on Day 29 (Up to Day 35) | 
| Number of Participants With Unsolicited Adverse Events for 28 Days After First Vaccination | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with study vaccine. Unsolicited adverse events included all adverse events for which the participant is not specifically questioned in the participant diary. | For 28 days after first vaccination on Day 1 (Up to Day 28) | 
| Number of Participants With Unsolicited Adverse Events for 28 Days After Second Vaccination | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with study vaccine. Unsolicited adverse events included all adverse events for which the participant is not specifically questioned in the participant diary. | For 28 days after second vaccination on Day 29 (Up to Day 56) | 
| Number of Participants With Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with study vaccine. SAE is any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. | From Day 1 (post-vaccination) to end of the study (up to 2 years 4 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers at Days 1, 29, 57 and 211 | RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay. | Day 1 (predose), Post-dose on Days 29, 57 and 211 | 
| Pre-Fusion RSV Fusion Protein (F-protein) Geometric Mean Titers (GMTs) as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) at Days 1, 29, 57 and 211 | GMT (ELISA units per liter [EU/L]) of RSV F protein in pre-fusion form as assessed by ELISA was reported. | Pre-fusion on Days 1, 29, 57 and 211 | 
| Post-Fusion RSV Fusion Protein (F-protein) Geometric Mean Titers (GMTs) as Assessed by ELISA at Days 1, 29, 57 and 211 | GMT (ELISA units per liter [EU/L]) of RSV F protein in post-fusion form as assessed by ELISA was reported. | Post-fusion on Days 1, 29, 57 and 211 | 
| Percentage of Cytokine Subsets (CD4, CD8, Th1 and Th2 Cytokines) to Evaluate Total Cytokine Response at Days 1, 29 and 57 | Total cytokine response (CD4, CD8, Th1 and Th2 Cytokines) after in vitro RSV F protein peptide stimulation was reported as the percentage of CD4+ and CD8+ T cells that produce at least 1 of 3 cytokines. | Day 1 (predose) and Post-dose on Days, 29, and 57 |