An Exploratory Study to Evaluate the Prophylactic Efficacy of a Single Immunization of Ad26.RSV.preF Against Respiratory Syncytial Virus Infection in a Virus Challenge Model in Healthy 18 to 50 Year-old Adults

Study Overview
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Brief Summary
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The purpose of this study is to assess a trend for the prophylactic efficacy of a single dose of 1*10^11 virus particles (vp) of adenovirus serotype 26 respiratory syncytial virus pre-fusion F protein (Ad26.RSV.preF) administered intramuscularly to adults aged 18-50 years in the respiratory syncytial virus (RSV) challenge model in terms of reduction of nasal wash viral load compared to placebo.

Official Title
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An Exploratory, Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Prophylactic Efficacy of a Single Immunization of Ad26.RSV.preF Against Respiratory Syncytial Virus Infection in a Virus Challenge Model in Healthy 18 to 50 Year-Old Adults

Conditions
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Healthy

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Each participant must sign an Informed Consent Form (ICF) indicating that he or she understands the purpose of and procedures required for the study, is willing to participate in the study and attend all scheduled visits, is willing to be isolated and stay in the clinic for the quarantine phase, and is willing and able to comply with all study procedures and adhere to the prohibitions and restrictions specified in this protocol Participants must be in good health, without significant medical illness, on the basis of a medical evaluation that reveals the absence of any clinically relevant abnormality and includes a physical examination (including height and weight), skin examination, medical history, vital signs (systolic and diastolic blood pressure and heart rate, respiratory rate, and body temperature), and the results of clinical laboratory tests performed within 56 days of vaccination. If there are abnormalities, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator Participants must have a non-clinically significant 12-lead electrocardiogram (ECG) within 56 days of vaccination including: normal sinus rhythm (heart rate between 50 and 100 beats per minute [bpm], extremes included); QT interval corrected for heart rate according to Fridericia (QTcF) interval less than or equal to (<=) 450 millisecond (ms); QT interval corrected for heart rate according to Bazett (QTcB) interval <= 450 ms; QRS interval less than (<) 120 ms; PR interval <= 210 ms Participants must be sero-suitable for respiratory syncytial virus (RSV) within 90 days of vaccination (low immunity to the RSV-A Memphis 37b virus using a virus neutralization assay Participant must be healthy on the basis of clinical laboratory tests performed within 56 days of vaccination. 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 US Food and Drug Administration (FDA) toxicity tables (that is, for tests in the FDA table), 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 Exclusion Criteria: Participant has acute illness (this does not include minor illnesses such as diarrhea) or temperature greater than or equal to (>=) 37.8 degree Centigrade within 24 hours prior to study vaccination Participant has history of malignancy (exceptions are basal cell carcinomas of the skin treated over 5 years prior to vaccination considered cured with minimal risk of recurrence) Participant has chronic active hepatitis B or hepatitis C infection, documented by hepatitis B surface antigen and hepatitis C antibody, respectively Viral Challenge Exclusion Criteria: Participants having donated or lost more than 1 unit of blood (470 milliliter [mL]) within 60 days or more than one unit of plasma within 7 days Participants with active acute respiratory infection

Ages Eligible for Study
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Minimum Age: 18 Years
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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Ad26.RSV.preF<br>Participants will receive single intramuscular injection of 1*10^11 virus particles (vp) of Ad26.RSV.preF during Day -90 to Day -28. On Day 0, intranasal challenge with respiratory syncytial virus (RSV)-A Memphis 37b virus will occur for all participants. | Biological: Ad26.RSV.preF<br>* Ad26.RSV.preF will be administered as intramuscular injection at a dose of 1*10^11 vp in single-use vials.<br>* Other names: JNJ-64400141;|
| Placebo Comparator: Group 2: Placebo<br>Participants will receive single intramuscular injection of placebo as sterile 0.9 percent (%) saline for injection during Day -90 to Day -28. On Day 0, intranasal challenge with RSV-A Memphis 37b virus will occur for all participants. | Drug: Placebo<br>* Placebo will be administered as sterile 0.9% saline for injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Viral Load-Time Curve (VL-AUC) of Respiratory Syncytial Virus (RSV) by Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) | VL-AUC for RSV was determined by qRT-PCR assay of nasal wash samples. Here, values below the lower limit of quantification (LLOQ) were imputed with zero. | From Day 2 to Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Viral Load of RSV-A Memphis 37b | Peak viral load of RSV-A Memphis 37b was defined as the maximum viral load as determined by quantitative RT-PCR assay of nasal wash samples. Here, values below the lower limit of quantification (LLOQ) were imputed with zero. | From Day 2 to Day 12 | 
| Viral Load by Quantitative RT-PCR Assay on Day 6 and 7 | Viral load determined by quantitative RT-PCR assay of nasal wash samples on Day 6 and Day 7 were reported. Here, values below the lower limit of quantification (LLOQ) were imputed with zero. | Day 6 (0 hour and 12 hours) and Day 7 (0 hour and 12 hours) | 
| VL-AUC of RSV by Quantitative Culture of RSV (Plaque Assay) on Day 6 and 7 | VL-AUC of RSV by the quantitative culture of nasal wash samples on Day 6 and Day 7 were determined. pfu*h/mL stands for plaque-forming units hour per millilitre. | Day 6 (0 hour and 12 hours) and Day 7 (0 hour and 12 hours) | 
| Percentage of Participants With Symptomatic RSV Infections | Symptomatic RSV infection is defined in two ways (Conservative and Liberal). Conservative: participant had 2 or more quantifiable RT-PCR measurements on different samples, with one of following: symptoms of 2 different categories of subject symptom card (SSC) (Upper Respiratory [runny/stuffy nose, sneezing, sore throat, earache], Lower Respiratory [cough, shortness of breath, chest tightness, wheeze], Systemic [malaise, headache, muscle and/or joint ache]) regardless of grade and assessment timepoint or Grade 2 symptom from any category; Liberal (RT-PCR): had 2/more quantifiable RT-PCR measurements, with clinical symptom of any severity. | From Day 2 to Day 12 | 
| Total Clinical Symptoms Score at Day 6 and 7 | The total clinical symptom score was determined as the sum of the scores (grades) ranges from 0 (no symptom) to 52 (severe symptoms) of the 13 self-reportable symptoms on the SSC. Clinical symptoms includes runny nose, stuffy nose, sneezing, sore throat, ear ache, malaise, headache, muscle and/or joint ache, chilliness/ feverishness, cough, chest tightness, shortness of breath and wheeze. For every separate symptom, the score ranges from 0 (I have no symptom) to 4 (its quite bothersome most of the times and stop from participating in activities). | Day 6 and 7: morning, afternoon and evening | 
| Weight of Mucus Secretions Over Time | The weight mucous over time was determined in grams using eCRF forms. Participants were given pre-weighed packets of paper tissues. After each tissue was used for nose blowing or sneezing, the participants should store them in an airtight plastic bag to calculate the weight of mucus from Day 0 to Day 12. All paper tissues used by each participant were collected for each 24-hour period up to Day 12, to determine daily mucus weight. | Day 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 | 
| Number of Tissues Used Over Time | Number of tissues used by participant per time point were reported using eCRF forms. Participants were given pre-weighed packets of paper tissues. After each tissue was used for nose blowing or sneezing, the participants should store them in an airtight plastic bag to calculate the number of tissues used from Day 0 to Day 12. All paper tissues used by each participant were collected for each 24-hour period up to Day 12, to determine daily number of tissues used. | Day 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 | 
| Percentage of Participants With Unsolicited Adverse Events (AEs) | Unsolicited AEs are all AEs for which participants were specifically not questioned in the participant diary. 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. | Up to 28 days post-vaccination and up to 28 days post-challenge | 
| Percentage of Participants With Serious Adverse Events (SAEs) | A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Up to 6 months post-vaccination and up to 6 months post-challenge | 
| Percentage of Participants With Solicited Local and Systemic AEs | Solicited local AEs: erythema, swelling/induration, and pain/tenderness. Solicited systemic AEs: fatigue, headache, myalgia, arthralgia, chills, nausea and fever. | 7 days post-vaccination (Day -21) | 
| Percentage of Participants With Vital Signs Abnormalities | Percentage of participants with vital signs abnormalities were reported. Vital signs measurements included body temperature (measured in degree celsius from less than [<] 37.5 to <39.5), respiratory rate, systolic and diastolic blood pressure, and pulse rate, which were graded by FDA Toxicity Grading Scale Grade 0 (=no grade), Grade 1 (=mild), Grade 2 (=moderate), Grade 3 (=severe) and Grade 4 (=potentially life-threatening). | Up to Day 28 post-challenge | 
| Percentage of Participants With Electrocardiogram (ECG) Abnormalities | ECG parameters included heart rate, PR, QRS, QTcB, QTcF, and the uncorrected QT interval which were graded by FDA Toxicity Grading Scale Grade 0 (=no grade), Grade 1 (=mild), Grade 2 (=moderate), Grade 3 (=severe) and Grade 4 (=potentially life-threatening). | Up to Day 12 post challenge | 
| Percentage of Participants With Clinical Laboratory Abnormalities (Graded) | Percentage of participants with clinical laboratory abnormalities were reported. The biochemical and hematological parameters analyzed were- Alanine aminotransferase (AA), Alkaline phosphatase (AP), Aspartate aminotransferase (AsP), Hyperkalemia, Hypernatremia, Hypoglycemia, Hypophosphatemia, Hemoglobin, Neutrophils, White blood cell (WBC) - increase and Urine protein, which were graded by FDA Toxicity Grading Scale Grade 0 (=no grade), Grade 1 (=mild), Grade 2 (=moderate), Grade 3 (=severe) and Grade 4 (=potentially life-threatening). | Up to Day 28 post-challenge |