Back to resultsAn 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
Primary Purpose
Healthy
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Ad26.RSV.preF
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Healthy
Eligibility Criteria
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
Sites / Locations
- hVIVO Services Limited
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Group 1: Ad26.RSV.preF
Group 2: Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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).
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).
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).
Full Information
NCT ID
NCT03334695
First Posted
October 16, 2017
Last Updated
July 1, 2021
Sponsor
Janssen Vaccines & Prevention B.V.
1. Study Identification
Unique Protocol Identification Number
NCT03334695
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
October 16, 2017 (Actual)
Primary Completion Date
July 10, 2018 (Actual)
Study Completion Date
November 27, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Vaccines & Prevention B.V.
4. Oversight
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
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
64 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1: Ad26.RSV.preF
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 2: Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Ad26.RSV.preF
Other Intervention Name(s)
JNJ-64400141
Intervention Description
Ad26.RSV.preF will be administered as intramuscular injection at a dose of 1*10^11 vp in single-use vials.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be administered as sterile 0.9% saline for injection.
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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)
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)
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
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
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
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
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
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
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)
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Vaccines & Prevention B.V. Clinical Trial
Organizational Affiliation
Janssen Vaccines & Prevention B.V.
Official's Role
Study Director
Facility Information:
Facility Name
hVIVO Services Limited
City
London
ZIP/Postal Code
E1 2AX
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
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
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