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

• Sponsor: Janssen Vaccines & Prevention B.V. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03334695
• Collaborator: (none)
• Enrollment: 64
• Location: 1
• Arms: 2
• Actual Duration (Months): 13.4
• Patients Per Site Per Month: 4.8

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Biological: Ad26.RSV.preF; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: Oct 16, 2017
• Actual Primary Completion Date: Jul 10, 2018
• Actual Study Completion Date: Nov 27, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: Ad26.RSV.preF 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; Ad26.RSV.preF will be administered as intramuscular injection at a dose of 1*10^11 vp in single-use vials.; Other Names: JNJ-64400141
Placebo Comparator: Group 2: Placebo 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; Placebo will be administered as sterile 0.9% saline for injection.

Outcome Measures

Primary Outcome Measures

1. Area Under the Viral Load-Time Curve (VL-AUC) of Respiratory Syncytial Virus (RSV) by Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) [From Day 2 to Day 12]

   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.

Secondary Outcome Measures

1. Peak Viral Load of RSV-A Memphis 37b [From Day 2 to Day 12]

   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.

2. Viral Load by Quantitative RT-PCR Assay on Day 6 and 7 [Day 6 (0 hour and 12 hours) and Day 7 (0 hour and 12 hours)]

   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.

3. VL-AUC of RSV by Quantitative Culture of RSV (Plaque Assay) on Day 6 and 7 [Day 6 (0 hour and 12 hours) and Day 7 (0 hour and 12 hours)]

   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.

4. Percentage of Participants With Symptomatic RSV Infections [From Day 2 to Day 12]

   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.

5. Total Clinical Symptoms Score at Day 6 and 7 [Day 6 and 7: morning, afternoon and evening]

   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).

6. Weight of Mucus Secretions Over Time [Day 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12]

   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.

7. Number of Tissues Used Over Time [Day 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12]

   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.

8. Percentage of Participants With Unsolicited Adverse Events (AEs) [Up to 28 days post-vaccination and up to 28 days post-challenge]

   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.

9. Percentage of Participants With Serious Adverse Events (SAEs) [Up to 6 months post-vaccination and up to 6 months post-challenge]

   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.

10. Percentage of Participants With Solicited Local and Systemic AEs [7 days post-vaccination (Day -21)]

    Solicited local AEs: erythema, swelling/induration, and pain/tenderness. Solicited systemic AEs: fatigue, headache, myalgia, arthralgia, chills, nausea and fever.

11. Percentage of Participants With Vital Signs Abnormalities [Up to Day 28 post-challenge]

    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).

12. Percentage of Participants With Electrocardiogram (ECG) Abnormalities [Up to Day 12 post challenge]

    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).

13. Percentage of Participants With Clinical Laboratory Abnormalities (Graded) [Up to Day 28 post-challenge]

    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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	hVIVO Services Limited	London		United Kingdom	E1 2AX

Sponsors and Collaborators

• Janssen Vaccines & Prevention B.V.

Investigators

• Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial, Janssen Vaccines & Prevention B.V.

Study Documents (Full-Text)

• Study Protocol - Jul 24, 2018
• Statistical Analysis Plan - Jul 30, 2018

More Information

Publications

None provided.

• Responsible Party: Janssen Vaccines & Prevention B.V.
• ClinicalTrials.gov Identifier: NCT03334695
• Other Study ID Numbers: CR108398; 2017-003194-33; VAC18193RSV2002
• First Posted: Nov 7, 2017
• Last Update Posted: Jul 23, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Virus Diseases; Respiratory Syncytial Virus Infections

Study Results

Participant Flow

Pre-assignment Detail	In total, 64 participants were screened. Of these, 63 participants were randomized and received the study vaccine. One participant was randomized in error and did not receive the study vaccine hence not included in the analyses.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Period Title: Overall Study
STARTED	31	32
COMPLETED	27	26
NOT COMPLETED	4	6

Baseline Characteristics

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo	Total
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Total of all reporting groups
Overall Participants	31	32	63
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.9 (6.19)	25.9 (6.56)	25.9 (6.33)
Sex: Female, Male (Count of Participants)
Female	12 38.7%	6 18.8%	18 28.6%
Male	19 61.3%	26 81.3%	45 71.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	30 96.8%	32 100%	62 98.4%
Unknown or Not Reported	1 3.2%	0 0%	1 1.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 9.7%	1 3.1%	4 6.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 3.2%	0 0%	1 1.6%
White	24 77.4%	28 87.5%	52 82.5%
More than one race	1 3.2%	0 0%	1 1.6%
Unknown or Not Reported	2 6.5%	3 9.4%	5 7.9%
Region of Enrollment (Count of Participants)
UNITED KINGDOM	31 100%	32 100%	63 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Viral Load-Time Curve (VL-AUC) of Respiratory Syncytial Virus (RSV) by Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR)
Description	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.
Time Frame	From Day 2 to Day 12

Outcome Measure Data

Analysis Population Description

The Intent-to-treat-Challenge (ITTc) population is a subset of the Full Analysis Set (FAS) (all participants who were randomized and received study vaccine, regardless of the occurrence of protocol deviations) included all randomized, vaccinated and challenged participants.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	27	26
Median (Inter-Quartile Range) [log10 copies*hour per millilitre (h/mL)]	0	236

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ad26.RSV.preF (1*10^11 vp), Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Wilcoxon Rank Sum test
	Comments

2. Secondary Outcome

Title	Peak Viral Load of RSV-A Memphis 37b
Description	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.
Time Frame	From Day 2 to Day 12

Outcome Measure Data

Analysis Population Description

The Intent-to-treat-Challenge (ITTc) population is a subset of the Full Analysis Set (FAS) (all participants who were randomized and received study vaccine, regardless of the occurrence of protocol deviations) included all randomized, vaccinated and challenged participants.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	27	26
Median (Inter-Quartile Range) [log10 copies per mL]	0.000	5.365

3. Secondary Outcome

Title	Viral Load by Quantitative RT-PCR Assay on Day 6 and 7
Description	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.
Time Frame	Day 6 (0 hour and 12 hours) and Day 7 (0 hour and 12 hours)

Outcome Measure Data

Analysis Population Description

The Intent-to-treat-Challenge (ITTc) population is a subset of the Full Analysis Set (FAS) (all participants who were randomized and received study vaccine, regardless of the occurrence of protocol deviations) included all randomized, vaccinated and challenged participants. Here 'n' (number analyzed) signifies the number of participants analyzed for this outcome measure (OM) at specified timepoints.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	27	26
Day 6: 0 hour	0.821 (0.349)	2.898 (0.630)
Day 6: 12 hour	1.261 (0.433)	2.939 (0.604)
Day 7: 0 hour	1.761 (0.436)	3.072 (0.586)
Day 7: 12 hour	1.552 (0.443)	3.025 (0.530)

4. Secondary Outcome

Title	VL-AUC of RSV by Quantitative Culture of RSV (Plaque Assay) on Day 6 and 7
Description	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.
Time Frame	Day 6 (0 hour and 12 hours) and Day 7 (0 hour and 12 hours)

Outcome Measure Data

Analysis Population Description

The Intent-to-treat-Challenge (ITTc) population is a subset of the Full Analysis Set (FAS) (all participants who were randomized and received study vaccine, regardless of the occurrence of protocol deviations) included all randomized, vaccinated and challenged participants. Here 'n' (number analyzed) signifies the number of participants analyzed for this OM at specified timepoints.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	27	26
Day 6: 0 hour	0.278 (0.1936)	1.587 (0.4159)
Day 6: 12 hour	0.304 (0.2198)	1.737 (0.4320)
Day 7: 0 hour	0.101 (0.1015)	1.226 (0.3505)
Day 7: 12 hour	0.276 (0.1931)	1.237 (0.3891)

5. Secondary Outcome

Title	Percentage of Participants With Symptomatic RSV Infections
Description	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.
Time Frame	From Day 2 to Day 12

Outcome Measure Data

Analysis Population Description

The Intent-to-treat-Challenge (ITTc) population is a subset of the Full Analysis Set (FAS) (all participants who were randomized and received study vaccine, regardless of the occurrence of protocol deviations) included all randomized, vaccinated and challenged participants.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	27	26
Conservative	22.2 71.6%	46.2 144.4%
Liberal	33.3 107.4%	61.5 192.2%

6. Secondary Outcome

Title	Total Clinical Symptoms Score at Day 6 and 7
Description	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).
Time Frame	Day 6 and 7: morning, afternoon and evening

Outcome Measure Data

Analysis Population Description

The Intent-to-treat-Challenge (ITTc) population is a subset of the Full Analysis Set (FAS) (all participants who were randomized and received study vaccine, regardless of the occurrence of protocol deviations) included all randomized, vaccinated and challenged participants.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	27	26
Day 6: Morning	0.6 (0.18)	2.6 (0.64)
Day 6: Afternoon	0.4 (0.18)	2.8 (0.74)
Day 6: Evening	0.5 (0.28)	2.5 (0.65)
Day 7: Morning	0.6 (0.23)	2.5 (0.70)
Day 7: Afternoon	0.6 (0.32)	2.5 (0.70)
Day 7: Evening	0.6 (0.32)	2.5 (0.63)

7. Secondary Outcome

Title	Weight of Mucus Secretions Over Time
Description	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.
Time Frame	Day 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12

Outcome Measure Data

Analysis Population Description

The Intent-to-treat-Challenge (ITTc) population is a subset of the Full Analysis Set (FAS) (all participants who were randomized and received study vaccine, regardless of the occurrence of protocol deviations) included all randomized, vaccinated and challenged participants. Here 'n' (number analyzed) signifies the number of participants analyzed for this OM at specified timepoints.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	27	26
Day 0	0.586 (0.1883)	0.175 (0.0913)
Day 1	0.228 (0.0621)	0.086 (0.0333)
Day 2	0.997 (0.2350)	0.428 (0.1459)
Day 3	0.970 (0.2176)	0.543 (0.1333)
Day 4	1.164 (0.3535)	0.714 (0.2123)
Day 5	1.440 (0.8609)	1.068 (0.3539)
Day 6	1.226 (0.4925)	3.132 (1.0991)
Day 7	1.715 (0.7201)	5.124 (1.3257)
Day 8	0.799 (0.2960)	3.230 (1.1022)
Day 9	1.004 (0.4147)	1.798 (0.4406)
Day 10	0.907 (0.3457)	1.785 (0.4838)
Day 11	0.749 (0.2430)	1.172 (0.3442)
Day 12	0.622 (0.2647)	0.990 (0.3005)

8. Secondary Outcome

Title	Number of Tissues Used Over Time
Description	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.
Time Frame	Day 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12

Outcome Measure Data

Analysis Population Description

The Intent-to-treat-Challenge (ITTc) population is a subset of the Full Analysis Set (FAS) (all participants who were randomized and received study vaccine, regardless of the occurrence of protocol deviations) included all randomized, vaccinated and challenged participants.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	27	26
Day 0	1.8 (0.53)	0.7 (0.33)
Day 1	1.7 (0.41)	0.7 (0.27)
Day 2	2.9 (0.65)	1.2 (0.32)
Day 3	1.9 (0.45)	1.3 (0.28)
Day 4	2.3 (0.49)	1.5 (0.31)
Day 5	2.1 (0.81)	2.3 (0.68)
Day 6	2.4 (0.77)	5.1 (1.59)
Day 7	2.8 (0.92)	8.1 (1.94)
Day 8	2.0 (0.71)	5.2 (1.38)
Day 9	2.3 (0.72)	2.8 (0.53)
Day 10	1.8 (0.61)	2.7 (0.61)
Day 11	1.6 (0.47)	2.0 (0.50)
Day 12	1.4 (0.40)	1.7 (0.45)

9. Secondary Outcome

Title	Percentage of Participants With Unsolicited Adverse Events (AEs)
Description	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.
Time Frame	Up to 28 days post-vaccination and up to 28 days post-challenge

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all participants who were randomized and received at least one dose of study vaccine, regardless of the occurrence of protocol deviations. Here 'n' (number analyzed) included all evaluable participants who were analyzed at specified categories.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	31	32
Post-vaccination	35.5 114.5%	46.9 146.6%
Post-challenge	74.1 239%	69.2 216.3%

10. Secondary Outcome

Title	Percentage of Participants With Serious Adverse Events (SAEs)
Description	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.
Time Frame	Up to 6 months post-vaccination and up to 6 months post-challenge

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all participants who were randomized and received at least one dose of study vaccine, regardless of the occurrence of protocol deviations. Here 'n' (number analyzed) included all evaluable participants who were analyzed at specified categories.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	31	32
Post-vaccination	0 0%	0 0%
Post-challenge	3.2 10.3%	0 0%

11. Secondary Outcome

Title	Percentage of Participants With Solicited Local and Systemic AEs
Description	Solicited local AEs: erythema, swelling/induration, and pain/tenderness. Solicited systemic AEs: fatigue, headache, myalgia, arthralgia, chills, nausea and fever.
Time Frame	7 days post-vaccination (Day -21)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all participants who were randomized and received at least one dose of study vaccine, regardless of the occurrence of protocol deviations.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	31	32
Solicited local AEs	100.0 322.6%	18.8 58.8%
Solicited systemic AEs	100.0 322.6%	50.0 156.3%

12. Secondary Outcome

Title	Percentage of Participants With Vital Signs Abnormalities
Description	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).
Time Frame	Up to Day 28 post-challenge

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all participants who were randomized and received at least one dose of study vaccine, regardless of the occurrence of protocol deviations. Here 'n' (number analyzed) included all evaluable participants who were analyzed at specified categories.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	31	32
Post-dose: Temperature (<37.5)	64.5 208.1%	93.8 293.1%
Post-dose: Temperature (37.5-<38.0)	22.6 72.9%	3.1 9.7%
Post-dose: Temperature (38.0-<38.5)	6.5 21%	0 0%
Post-dose: Temperature (38.5-<39.0)	6.5 21%	3.1 9.7%
Post-dose: Bradycardia (pulse): Grade 1	12.9 41.6%	3.1 9.7%
Post-dose: Bradycardia (pulse): Grade 2	6.5 21%	6.3 19.7%
Post-dose: Bradycardia (pulse): Grade 3/4	3.2 10.3%	0 0%
Post-dose: Hypertension (diastolic): Grade 1	0 0%	3.1 9.7%
Post-dose: Hypertension (diastolic): Grade 2	6.5 21%	0 0%
Post-dose: Hypertension (systolic): Grade 1	3.2 10.3%	3.1 9.7%
Post-dose: Respiratory rate: Grade 1	25.8 83.2%	18.8 58.8%
Post-dose: Tachycardia (pulse): Grade 1	3.2 10.3%	0 0%
Post-challenge: Bradycardia (pulse): Grade 1	18.5 59.7%	11.5 35.9%
Post-challenge: Bradycardia (pulse): Grade 2	3.7 11.9%	3.8 11.9%
Post-challenge: Bradycardia (pulse): Grade 3/4	3.7 11.9%	0 0%
Post-challenge: Hypertension (diastolic): Grade 1	3.7 11.9%	0 0%
Post-challenge: Hypertension (systolic): Grade 1	0 0%	7.7 24.1%
Post-challenge: Respiratory rate: Grade 1	25.9 83.5%	26.9 84.1%
Post-challenge: Tachycardia (pulse): Grade 1	3.7 11.9%	0 0%

13. Secondary Outcome

Title	Percentage of Participants With Electrocardiogram (ECG) Abnormalities
Description	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).
Time Frame	Up to Day 12 post challenge

Outcome Measure Data

Analysis Population Description

The Intent-to-treat-Challenge (ITTc) population is a subset of the Full Analysis Set (FAS) (all participants who were randomized and received study vaccine, regardless of the occurrence of protocol deviations) included all randomized, vaccinated and challenged participants.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	27	26
Heart rate: Abnormally low: Grade 1	0 0%	3.8 11.9%
Heart rate: Abnormally low: Grade 2	0 0%	3.8 11.9%
QTc Bazett (450 millisecond [ms], 480 ms)	0 0%	3.8 11.9%
QTc Bazett (increase from baseline [30; 60] ms)	7.4 23.9%	11.5 35.9%
QTc Fridericia: (increase from baseline [30; 60] ms)	3.7 11.9%	0 0%

14. Secondary Outcome

Title	Percentage of Participants With Clinical Laboratory Abnormalities (Graded)
Description	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).
Time Frame	Up to Day 28 post-challenge

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) included all participants who were randomized and received at least one dose of study vaccine, regardless of the occurrence of protocol deviations. Here 'n' (number analyzed) signifies the number of participants analyzed for this OM at specified categories.

Arm/Group Title	Ad26.RSV.preF (1*10^11 vp)	Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of adenovirus serotype 26 respiratory syncytial virus pre-fusion conformation-stabilized F protein (Ad26.RSV.preF) on Day -28 followed by intranasal challenge with a respiratory syncytial virus (RSV)-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).	Participants received a single intramuscular injection of matching placebo on Day -28 followed by intranasal challenge with RSV-A Memphis 37b virus on Day 0 (24 to 90 days after vaccination).
Measure Participants	31	32
Post Dose: AA: Grade 1	9.7 31.3%	0 0%
Post Dose: AP: Grade 1	0 0%	3.1 9.7%
Post Dose: AsA: Grade 1	6.5 21%	0 0%
Post Dose: AsA: Grade 2	0 0%	3.1 9.7%
Post Dose: Hyperkalemia: Grade 2	3.2 10.3%	0 0%
Post Dose: Hypernatremia: Grade 2	3.2 10.3%	0 0%
Post Dose: Hypoglycemia: Grade 2	0 0%	3.1 9.7%
Post Dose: Hypophosphatemia:Grade 1	3.2 10.3%	0 0%
Post Dose: Hypophosphatemia:Grade 2	9.7 31.3%	0 0%
Post Dose: Hemoglobin: Grade 1	3.2 10.3%	3.1 9.7%
Post Dose: Hemoglobin: Grade 2	3.2 10.3%	0 0%
Post Dose: Neutrophils: Grade 1	12.9 41.6%	6.3 19.7%
Post Dose: WBC increase: Grade 1	0 0%	3.1 9.7%
Post Dose: Urine Protein: Grade 1	3.2 10.3%	3.1 9.7%
Post Challenge: AA: Grade 1	25.9 83.5%	15.4 48.1%
Post Challenge: AA: Grade 2	7.4 23.9%	3.8 11.9%
Post Challenge: AP: Grade 1	0 0%	3.8 11.9%
Post Challenge: AsA: Grade 1	14.8 47.7%	15.4 48.1%
Post Challenge: AsA: Grade 2	3.7 11.9%	3.8 11.9%
Post Challenge: AsA: Grade 4	0 0%	3.8 11.9%
Post Challenge: Bilirubin: Grade 2	3.7 11.9%	0 0%
Post Challenge: Hyperglycemia: Grade 1	0 0%	3.8 11.9%
Post Challenge: Hyperkalemia: Grade 1	3.7 11.9%	3.8 11.9%
Post Challenge: Hypernatremia: Grade 2	3.7 11.9%	0 0%
Post Challenge: Hypophosphatemia:Grade 1	3.7 11.9%	0 0%
Post Challenge: Hypoproteinemia:Grade 1	11.1 35.8%	0 0%
Post Challenge: Eosinophils: Grade 1	0 0%	7.7 24.1%
Post Challenge: Hemoglobin: Grade 1	7.4 23.9%	0 0%
Post Challenge: Neutrophils: Grade 1	7.4 23.9%	0 0%
Post Challenge: Platelets: Grade 1	3.7 11.9%	3.8 11.9%
Post Challenge: Platelets: Grade 20	0 0%	3.8 11.9%
Post Challenge: WBC increase: Grade 1	3.7 11.9%	0 0%

Adverse Events

Time Frame	Up to 6 months post-vaccination and up to 6 months post-challenge
Adverse Event Reporting Description	The full analysis set (FAS) included all participants who were randomized and received at least one dose of study vaccine, regardless of the occurrence of protocol deviations.
Arm/Group Title	Post-dose: Ad26.RSV.preF (1x10^11 vp)		Post-dose: Placebo		Post-challenge: Challenge After Ad26.RSV.preF		Post-challenge: Challenge After Placebo
Arm/Group Description	Participants received a single intramuscular injection of 1*10^11 vp (viral particles) of Ad26.RSV.preF on Day -28.		Participants received a single intramuscular injection of matching placebo on Day -28.		Participants undergone intranasal challenge with RSV-A Memphis 37b virus on Day 0, after receiving single intramuscular doses of 1x1011 vp of Ad26.RSV.preF on Day -28.		Participants undergone intranasal challenge with RSV-A Memphis 37b virus on Day 0, after receiving single intramuscular doses of placebo on Day -28.
All Cause Mortality
	Post-dose: Ad26.RSV.preF (1x10^11 vp)		Post-dose: Placebo		Post-challenge: Challenge After Ad26.RSV.preF		Post-challenge: Challenge After Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/32 (0%)		0/27 (0%)		0/26 (0%)
Serious Adverse Events
	Post-dose: Ad26.RSV.preF (1x10^11 vp)		Post-dose: Placebo		Post-challenge: Challenge After Ad26.RSV.preF		Post-challenge: Challenge After Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/31 (0%)		0/32 (0%)		1/27 (3.7%)		0/26 (0%)
Reproductive system and breast disorders
Ovarian Cyst	0/31 (0%)		0/32 (0%)		1/27 (3.7%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Post-dose: Ad26.RSV.preF (1x10^11 vp)		Post-dose: Placebo		Post-challenge: Challenge After Ad26.RSV.preF		Post-challenge: Challenge After Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/31 (12.9%)		9/32 (28.1%)		16/27 (59.3%)		16/26 (61.5%)
Blood and lymphatic system disorders
Lymphadenopathy	0/31 (0%)		0/32 (0%)		6/27 (22.2%)		1/26 (3.8%)
Gastrointestinal disorders
Nausea	0/31 (0%)		0/32 (0%)		0/27 (0%)		2/26 (7.7%)
Infections and infestations
Pharyngitis	0/31 (0%)		0/32 (0%)		3/27 (11.1%)		4/26 (15.4%)
Injury, poisoning and procedural complications
Sunburn	0/31 (0%)		2/32 (6.3%)		0/27 (0%)		0/26 (0%)
Investigations
Alanine Aminotransferase Increased	2/31 (6.5%)		0/32 (0%)		7/27 (25.9%)		3/26 (11.5%)
Aspartate Aminotransferase Increased	2/31 (6.5%)		1/32 (3.1%)		2/27 (7.4%)		2/26 (7.7%)
Troponin T Increased	0/31 (0%)		0/32 (0%)		0/27 (0%)		2/26 (7.7%)
Nervous system disorders
Headache	1/31 (3.2%)		4/32 (12.5%)		2/27 (7.4%)		2/26 (7.7%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/31 (0%)		0/32 (0%)		0/27 (0%)		3/26 (11.5%)
Oropharyngeal Pain	1/31 (3.2%)		1/32 (3.1%)		0/27 (0%)		2/26 (7.7%)
Rhinorrhoea	0/31 (0%)		0/32 (0%)		1/27 (3.7%)		4/26 (15.4%)
Skin and subcutaneous tissue disorders
Dry Skin	1/31 (3.2%)		1/32 (3.1%)		3/27 (11.1%)		2/26 (7.7%)

Limitations/Caveats

As no respiratory syncytial virus (RSV) vaccine has been previously tested in a human challenge model, the relationship between the results from this human challenge model and vaccine efficacy against natural infection is unknown.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation.