A Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Adenovirus Serotype 26 Based Respiratory Syncytial Virus Pre-fusion (Ad26.RSV.Pre-F) Vaccine in RSV-Seronegative 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 reactogenicity of an intramuscular regimen of 3 doses of 2.5*10^10 viral particles (vp) of adenovirus serotype 26 based respiratory syncytial virus pre-fusion protein (Ad26.RSV.preF) vaccine in RSV-seronegative toddlers aged 12 to 24 months.

Detailed Description
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RSV is considered the most important cause of serious acute respiratory illness in children under 5 years of age. Ad26.RSV.preF (JNJ-64400141) investigational vaccine is a replication-incompetent serotype 26 adenoviral vector (Ad26) containing a deoxyribonucleic acid (DNA) transgene that encodes for the F protein derived from the respiratory syncytial virus (RSV) A2 strain stabilized in the pre-fusion conformation (Ad26.RSV.preF). The study will evaluate whether Ad26.RSV.preF is safe, well-tolerated, and immunogenic in RSV-seronegative toddlers. The study will have 3 phases: a screening phase (up to 6 weeks before the first dose), a vaccination phase (34 weeks), and a safety follow-up phase through 2 RSV seasons after the first dose. RSV infection will be monitored by active and passive surveillance. The total duration of the study will be approximately 26 months.

Official Title
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A Randomized, Controlled, Observer-blind, Phase 1/2a Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26.RSV.preF in RSV-seronegative Toddlers 12 to 24 Months of Age

Conditions
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Respiratory Syncytial Virus

Intervention / Treatment
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* Biological: Ad26.RSV.preF
* Biological: Placebo
* Biological: Nimenrix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant who is seronegative for respiratory syncytial virus (RSV) within 42 days prior to dosing Participant is the product of a normal term pregnancy greater than or equal to (>=)37 weeks, with a minimum birth weight of 2.5 kilogram (kg) Participant must be in good health without any significant medical illness on the basis of physical examination, medical history, and vital signs performed at screening Participant has received all routine immunizations appropriate for his or her age according to local guidelines Each participant's parent(s)/legal guardian(s) must have access to a consistent means of contact either by telephone contact or email/computer Exclusion Criteria: Participant's weight is below tenth percentile according to World Health Organization (WHO) pediatric growth and weight charts Participant has any clinically significant acute or chronic medical condition (for 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 beta 2 agonist, cystic fibrosis, bronchopulmonary dysplasia, chronic pulmonary disease, medically-confirmed apnea, hospitalization for respiratory illness, or mechanical ventilation for respiratory illness) that, in the opinion of the investigator, would preclude participation Participant is in receipt of, or planning to receive, live attenuated vaccine (for example, measles, mumps and rubella [MMR] or varicella, but excluding rotavirus vaccine) within 28 days of each study vaccination (that is, before and after); other vaccines (for example, influenza, pertussis, polio or rotavirus) should be given at least 14 days before or 14 days after each study vaccination Participant has known or suspected immunodeficiency, such as known human immunodeficiency virus (HIV) infection Participant has a known allergy to vaccines or vaccine components (including any of the constituents of the study vaccine), or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine components (including any of the constituents of the study vaccine). Participants with egg allergies can be enrolled

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 24 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: RSV Seronegative Toddlers (Ad26.RSV.preF)<br>Respiratory syncytial virus (RSV) seronegative toddlers will receive intramuscular (IM) injection of 2.5*10^10 viral particles (vp) of an adenovirus serotype 26- based vaccine encoding for the respiratory syncytial virus pre-fusion F-protein on Days 1, 29, and 57. | Biological: Ad26.RSV.preF<br>* Ad26.RSV.preF will be administered as IM injection at a dose of 2.5*10^10 vp.<br>* Other names: JNJ-64400141;|
| Placebo Comparator: Group 2: RSV Seronegative Toddlers (Placebo/Nimenrix)<br>RSV seronegative toddlers will receive IM injection of placebo on Days 1, 29 and 57. Placebo can be replaced with Nimenrix on Day 57 in countries where applicable. | Biological: Placebo<br>* Placebo will be administered as IM injection of sterile 0.9 percent (%) saline for injection.<br>Biological: Nimenrix<br>* Nimenrix will be administered as 0.5 milliliter (mL) solution for IM injection.<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 and Systemic Adverse Events (AEs) for 7 Days After First Vaccination | An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. Solicited local and systemic AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included injection-site pain/tenderness, injection-site erythema and injection-site swelling/induration. Solicited systemic AEs included fatigue, headache, nausea, myalgia and fever. | Up to Day 8 (7 days after first vaccination on Day 1) | 
| Number of Participants With Solicited Local and Systemic AEs for 7 Days After Second Vaccination | An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. Solicited local and systemic AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included injection-site pain/tenderness, injection-site erythema and injection-site swelling/induration. Solicited systemic AEs included fatigue, headache, nausea, myalgia and fever. | Up to Day 36 (7 days after second vaccination on Day 29) | 
| Number of Participants With Solicited Local and Systemic AEs for 7 Days After Third Vaccination | An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. Solicited local and systemic AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included injection-site pain/tenderness, injection-site erythema and injection-site swelling/induration. Solicited systemic AEs included fatigue, headache, nausea, myalgia and fever. | Up to Day 64 (7 days after third vaccination on Day 57) | 
| Number of Participants With Unsolicited AEs for 28 Days After First Vaccination | An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. Unsolicited AEs were precisely defined events that participants were not asked about and which were not noted by participants in the diary. | Up to Day 29 (28 days after first vaccination on Day 1) | 
| Number of Participants With Unsolicited AEs for 28 Days After Second Vaccination | An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. Unsolicited AEs were precisely defined events that participants were not asked about and which were not noted by participants in the diary. | Up to Day 57 (28 days after second vaccination on Day 29) | 
| Number of Participants With Unsolicited AEs for 28 Days After Third Vaccination | An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. Unsolicited AEs were precisely defined events that participants were not asked about and which were not noted by participants in the diary. | Up to Day 85 (28 days after third vaccination on Day 57) | 
| Number of Participants With Serious Adverse Events (SAEs) | Number of participants with SAEs were reported. An AE is any untoward medical event that occurs in a participants administered an investigational product, and it does not necessarily indicate only events with a clear causal relationship with the relevant investigational product. SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a suspected transmission of any infectious agent via a medicinal product, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above. | Up to 2 year 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Titers of Neutralizing Antibodies to Respiratory Syncytial Virus (RSV) A2 Strain | Neutralizing antibody titers assessed by virus neutralizing antibodies (VNA) against the RSV A2 strain were expressed as 50% inhibitory concentration (IC50) units. | Days 1, 8, 85, and 267 (End of first RSV season) | 
| Pre-Fusion A Immunoglobulin G (IgG) Serum Antibody Response as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | Pre-fusion A IgG serum antibody response was assessed by ELISA. | Days 1, 8, 85, and 267 (End of first RSV season) | 
| Post-Fusion A IgG Serum Antibody Response as Assessed by ELISA | Post-fusion A IgG serum antibody response as assessed by ELISA was reported. | Days 1, 8, 85, and 267 (End of first RSV season) | 
| T-cell Response (Percent [%]) to RSV F Peptides for T-helper (Th) 1 and Th2 Subtyping as Measured by Flow Cytometry | T-cell response (%) to RSV F peptides for T-helper Th1 and Th2 subtyping as measured by flow cytometry was planned to be assessed. Th1(% of Clusters of differentiation 4 [CD4]+ interferon gamma [IFN-g]+T cells; lower limit(s) of quantification [LLOQ]=0.05%) and Th2 (% of CD4+ interleukin [IL]-4+/IL-13+ and CD40L+T cells; LLOQ=0.07%) responses were determined by intracellular cytokines after RSV F peptide stimulation. | Baseline (Day 1) and Day 85 | 
| Number of Participants With Severe RSV-lower Respiratory Tract Infection (LRTI) | Number of participants with severe RSV-LRTI were reported. | Up to 2 year 10 months |