A Study of an Ad26.RSV.preF-based Regimen in the Prevention of Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-Confirmed Respiratory Syncytial Virus (RSV)-Mediated Lower Respiratory Tract Disease in Adults Aged 65 Years and Older
- Conditions
- Respiratory Syncytial VirusesRespiratory Tract Diseases
- Interventions
- Biological: Placebo
- Registration Number
- NCT03982199
- Lead Sponsor
- Janssen Vaccines & Prevention B.V.
- Brief Summary
The purpose of this study is to demonstrate the efficacy of active study vaccine in the prevention of reverse transcriptase polymerase chain reaction (RT-PCR) confirmed respiratory syncytial virus (RSV)-mediated lower respiratory tract disease (LRTD), when compared to placebo.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 5815
- Participant must have a body mass index (BMI) less than (<)40 kilogram per meter square (kg/m^2)
- Before randomization, a woman must be: postmenopausal (postmenopausal state is defined as no menses for 12 months without an alternative medical cause); and not intending to conceive by any methods
- Participant must be either in good or stable health. Participants may have mild to moderate underlying illnesses such as chronic cardiac diseases and chronic lung disease (asthma and chronic obstructive pulmonary disease [COPD]), congestive heart failure (CHF), hypertension, type 2 diabetes mellitus, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms and signs are stable and medically controlled in the judgment of the investigator. Participants will be included on the basis of physical examination, medical history, and vital signs performed between informed consent form (ICF) signature and vaccination on Day 1
- From the time of vaccination through 3 months after vaccination, participant agrees not to donate blood
- Participant must be able to read, understand, and complete questionnaires in the eDiary (or a paper safety diary, if designated by the sponsor)
- Participant must be willing to provide verifiable identification, have means to be contacted and to contact the investigator during the study
- Participant has an acute illness (including acute respiratory illnesses) or body temperature greater than or equal to (>=)38.0 degree Celsius (ºC) within 24 hours prior to administration of study vaccine. In such a situation, enrollment at a later date is permitted
- Participant has a severe or potentially life-threatening chronic disorder such as severe chronic cardiac diseases and severe chronic lung disease (asthma and COPD), advanced CHF, end-stage renal disease with or without dialysis, clinically unstable cardiac disease, Alzheimer's disease, or has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example: compromise well-being) or that could prevent, limit, or confound the protocol-specified assessments
- Participant has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
- Per medical history, participant has chronic active hepatitis B or hepatitis C infection
- Per medical history, participant has human immunodeficiency virus (HIV) type 1 or type 2 infection
- Participant has a known allergy, or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine components (including any of the constituents of the study vaccine)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 2: Placebo RSV Vaccine Participants will receive a single IM injection of placebo control on Day 1. Participants will then be divided into revaccination subcohorts 2A, 2B, and 2C, and will first receive Ad26.RSV.preF based vaccine at years 1, 2, and 3. In subcohorts 2A and 2B, participants will receive a revaccination one year later with either Ad26.RSV.preF based vaccine, study vaccine A or study vaccine B. Group 2: Placebo Placebo Participants will receive a single IM injection of placebo control on Day 1. Participants will then be divided into revaccination subcohorts 2A, 2B, and 2C, and will first receive Ad26.RSV.preF based vaccine at years 1, 2, and 3. In subcohorts 2A and 2B, participants will receive a revaccination one year later with either Ad26.RSV.preF based vaccine, study vaccine A or study vaccine B. Group 1: RSV Vaccine RSV Vaccine Participants will receive a single intramuscular (IM) injection of an adenovirus serotype 26 (Ad26)-based respiratory syncytial virus (RSV) vaccine at a single dose level on Day 1. Participants will then be divided into revaccination subcohorts: 1A, 1B, and 1C to receive revaccination with Ad26.RSV.preF based vaccine at 1 year, 2 years, and 3 years respectively after the first vaccination.
- Primary Outcome Measures
Name Time Method Number of Participants With First Occurrence of Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)-Confirmed Respiratory Syncytial Virus (RSV) Mediated Lower Respiratory Tract Disease (LRTD) From screening (Day 1) up to 9 months Number of participants with first occurrence of RT-PCR-confirmed RSV mediated LRTD according to case definition-1, 2 and 3 were reported. Case definition 1 was defined as having a new onset or worsening in 3 or more symptoms of lower respiratory tract infection (LRTI) ; Case definition 2 was defined as having a new onset or worsening in greater than or equal to (\>=) 2 symptoms of LRTI; and Case definition 3 was defined as having a new onset or worsening in \>=2 OR \>=1 symptoms of LRTI with \>=1 systemic symptoms. Systemic symptoms (fatigue/malaise and fever/feverishness) and symptoms of LRTI (cough, shortness of breath, sputum production, wheezing and tachypnea) were collected via the RiiQ. RiiQ symptom scale was a 13-items questionnaire rated on a 4-point scale. Each symptom was rated on a scale of 0 to 3 where 0=None, 1=Mild, 2=Moderate, and 3=Severe. Higher scores indicated greater severity. The total LRTD symptom score was calculated as the mean of the LRTD symptom scores.
- Secondary Outcome Measures
Name Time Method Main Cohorts: Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers Days 15, 85, 169, 365 RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay.
Main Cohorts: Number of Participants With Unsolicited AEs up to 28 Days After First Vaccination Up to Day 29 (28 days after first vaccination on Day 1) An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Unsolicited adverse events included all adverse events for which the participant is not specifically questioned in the participant diary.
Revaccination Subcohorts: Number of Participants With Solicited Local AEs 7 Days After Re-vaccination up to 1, 2 and 3 Years Arms 3,4: 7 days after revacc at 1 year (up to Day 372); Arm 5,6,7,8,9: 7 days after revacc at 2 years (up to Day 737); Arms 10,11,12,13,14: 7 days after revacc at 3 year (up to Day 1102) Number of participants with solicited local AEs 7 days after re-vaccination at 1, 2 and 3 years were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited local AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included erythema, swelling/induration, and pain/tenderness. Per protocol, all solicited local AEs were considered as related to intervention.
Main Cohorts: Number of Participants With Any RT-PCR-confirmed RSV Disease From screening (Day 1) up to 9 months Number of participants with any RT-PCR-confirmed RSV disease were reported. The analysis was based on poisson regression model.
Revaccination Subcohorts: Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers Days 15, 365, 379, 393, 449, 730, 737, 744, 758 RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay.
Revaccination Subcohort 2A: T-cell Interferon (IFN) Gamma Responses to RSV F Protein Peptides Analyzed by Enzyme-linked Immunospot Assay (ELISpot) Days 730, 744, 758 T-cell IFN gamma responses to RSV F protein specific peptides as measured by ELISpot assay were reported. RSV F protein specific T-cell IFN gamma ELISpot responses were measured as counts of spot forming cells per million peripheral blood mononuclear cells (SFC/10\^6 PBMCs).
Main Cohorts: T-cell Interferon (IFN) Gamma Responses to RSV F Protein Peptides Analyzed by Enzyme-linked Immunospot Assay (ELISpot) Days 15, 85, 169, 365, 533 T-cell IFN gamma responses to RSV F protein specific peptides as measured by ELISpot assay were reported. RSV F protein specific T-cell IFN gamma ELISpot responses were measured as counts of spot forming cells per million peripheral blood mononuclear cells (SFC/10\^6 PBMCs).
Main Cohorts: Number of Participants With Solicited Local Adverse Events (AEs) up to 7 Days After First Vaccination Up to Day 8 (7 days after first vaccination on Day 1) An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited local AEs were precisely defined events that participants were specifically asked about and which were noted by participants in the diary. Solicited local AEs included erythema, swelling/induration, and pain/tenderness. Per protocol, all solicited local AEs were considered as related to intervention.
Main Cohorts: Number of Participants With Solicited Systemic AEs up to 7 Days After First Vaccination Up to Day 8 (7 days after first vaccination on Day 1) An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited systemic AEs included fatigue, headache, myalgia, arthralgia, and fever (defined as an endogenous elevation of body temperature \>=38.0°C, as recorded in at least one measurement).
Revaccination Subcohorts: Geometric Mean Titers (GMTs) of Prefusion F-protein (Pre-F) A Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) Day 15: Arms 3 to 7,13 and 14; Days 365, 379, 393, 449, 533: Arms 3 to 7; Day 730: Arms 4 to 7; Days 737, 744, 758: Arms 5 to 7; Day 1095, 1109: Arms 13 and 14 GMTs of preF-A antibodies after the administration of Ad26.RSV.preF-based vaccine as assessed by ELISA were reported.
Revaccination Subcohorts: Number of Participants With Solicited Systemic AEs 7 Days After Re-vaccination up to 1, 2 and 3 Years Arms 3,4: 7 days after revacc at 1 year (up to Day 372); Arm 5,6,7,8,9: 7 days after revacc at 2 years (up to Day 737); Arms 10,11,12,13,14: 7 days after revacc at 3 year (up to Day 1102) Number of participants with solicited systemic AEs 7 days after re-vaccination up to 1, 2 and 3 years were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Solicited systemic AEs included fatigue, headache, myalgia, arthralgia, and fever (defined as an endogenous elevation of body temperature \>=38.0°C, as recorded in at least one measurement).
Revaccination Subcohorts: Number of Participants With Unsolicited AEs 28 Days After Re-vaccination up to 1, 2 and 3 Years Arms 3,4: 28 days after revacc at 1 year (up to Day 393); Arms 5,6,7,8,9: 28 days after revacc at 2 years (up to Day 758); Arms 10,11,12,13,14: 28 days after revaccination at 3 year (up to Day 1123) An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. Unsolicited adverse events included all adverse events for which the participant is not specifically questioned in the participant diary.
Revaccination Subcohorts: Number of Participants With Adverse Events of Special Interests (AESI) Arms 3,4: 6 months after revacc at 1 year (up to Day 547); Arm 5,6,7,8,9: 6 months after revacc at 2 years (up to Day 912); Arms 10,11,12,13,14: 6 months after revacc at 3 year (up to Day 1277) Number of participants with AESIs were reported. An AE was any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Thrombosis with thrombocytopenia syndrome (TTS) was considered as an AESI.
Main Cohorts: Geometric Mean Titers (GMTs) of Prefusion F-protein (Pre-F) A Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA) Days 15, 85, 169, 365, 533 GMTs of preF-A antibodies after the administration of Ad26.RSV.preF-based vaccine as assessed by ELISA were reported.
Main Cohorts:Number of Participants With Serious Adverse Events (SAEs) From Day 1 up to Day 1095 An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An 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/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. For participants who were not revaccinated only SAEs associated with ARIs and complications related to ARIs that classify as SAEs, SAEs classified as related, SAEs resulting in death, and (S)AEs resulting in study discontinuation or from procedures and non-investigational (concomitant) Janssen products were collected.
Revaccination Subcohorts: Number of Participants With Serious Adverse Events (SAEs) Arms 3,4: 6 months after revacc at 1 year (up to Day 547); Arm 5,6,7,8,9: 6 months after revacc at 2 years (up to Day 912); Arms 10,11,12,13,14: 6 months after revacc at 3 year (up to Day 1277) An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An 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/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.
Trial Locations
- Locations (22)
Rapid Medical Research
🇺🇸Cleveland, Ohio, United States
Johnson County Clin-Trials
🇺🇸Lenexa, Kansas, United States
Lynn Institute
🇺🇸Colorado Springs, Colorado, United States
Anaheim Clinical Trials, LLC
🇺🇸Anaheim, California, United States
Heartland Research Associates, LLC
🇺🇸Wichita, Kansas, United States
Hutchinson Clinic
🇺🇸Hutchinson, Kansas, United States
Paradigm Clinical Research Centers, Inc.
🇺🇸Redding, California, United States
University of Rochester / Rochester General Hospital
🇺🇸Rochester, New York, United States
The Iowa Clinic
🇺🇸West Des Moines, Iowa, United States
United Medical Associates
🇺🇸Binghamton, New York, United States
Sundance Clinical Research
🇺🇸Saint Louis, Missouri, United States
Regional Clinical Research, Inc.
🇺🇸Endwell, New York, United States
Omega Medical Research
🇺🇸Warwick, Rhode Island, United States
Ventavia Research Group, LLC
🇺🇸Fort Worth, Texas, United States
Coastal Carolina Research Center
🇺🇸Mount Pleasant, South Carolina, United States
Advanced Clinical Research
🇺🇸West Jordan, Utah, United States
Synexus Clinical Research US Inc
🇺🇸Murray, Utah, United States
Optimal Research
🇺🇸Austin, Texas, United States
Central Phoenix Medical Clinic
🇺🇸Phoenix, Arizona, United States
Benchmark Research
🇺🇸Sacramento, California, United States
The Center For Pharmaceutical Research
🇺🇸Kansas City, Missouri, United States
Lynn Health Science Institute
🇺🇸Oklahoma City, Oklahoma, United States