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

Phase 2TerminatedNCT03982199

Janssen Vaccines & Prevention B.V.5,815 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

5,815

Conditions

Respiratory Syncytial Viruses Respiratory Tract Diseases

Interventions

RSV Vaccine

Eligibility

Sex: ALLMin age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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)

Locations (40)

Optimal Research

Huntsville, Alabama, United States

Synexus Clinical Research US Inc

Chandler, Arizona, United States

Synexus Clinical Research US Inc

Phoenix, Arizona, United States

Central Phoenix Medical Clinic

Phoenix, Arizona, United States

Anaheim Clinical Trials, LLC

Anaheim, California, United States

Outcomes

Primary Outcomes

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)

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.

Time frame: From screening (Day 1) up to 9 months

Secondary Outcomes

Main Cohorts: Number of Participants With Any RT-PCR-confirmed RSV Disease

Number of participants with any RT-PCR-confirmed RSV disease were reported. The analysis was based on poisson regression model.

Time frame: From screening (Day 1) up to 9 months

Main Cohorts: Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers

RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay.

Time frame: Days 15, 85, 169, 365

Revaccination Subcohorts: Respiratory Syncytial Virus (RSV) A2 Strain Neutralization Antibody Titers

RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay.

Time frame: Days 15, 365, 379, 393, 449, 730, 737, 744, 758

Revaccination Subcohorts: Geometric Mean Titers (GMTs) of Prefusion F-protein (Pre-F) A Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)

GMTs of preF-A antibodies after the administration of Ad26.RSV.preF-based vaccine as assessed by ELISA were reported.

Time frame: 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

Revaccination Subcohort 2A: T-cell Interferon (IFN) Gamma Responses to RSV F Protein Peptides Analyzed by Enzyme-linked Immunospot Assay (ELISpot)

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).

Time frame: Days 730, 744, 758

Main Cohorts: T-cell Interferon (IFN) Gamma Responses to RSV F Protein Peptides Analyzed by Enzyme-linked Immunospot Assay (ELISpot)

Time frame: Days 15, 85, 169, 365, 533

Main Cohorts: Number of Participants With Solicited Local Adverse Events (AEs) up to 7 Days After First Vaccination

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.

Time frame: Up to Day 8 (7 days after first vaccination on Day 1)

Main Cohorts: Number of Participants With Solicited Systemic AEs up to 7 Days After First Vaccination

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).

Time frame: Up to Day 8 (7 days after first vaccination on Day 1)

Main Cohorts: Number of Participants With Unsolicited AEs up to 28 Days After First Vaccination

Time frame: Up to Day 29 (28 days after first vaccination on Day 1)

Revaccination Subcohorts: Number of Participants With Solicited Local AEs 7 Days After Re-vaccination up to 1, 2 and 3 Years

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.

Time frame: 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)

Revaccination Subcohorts: Number of Participants With Solicited Systemic AEs 7 Days After Re-vaccination up to 1, 2 and 3 Years

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).

Time frame: 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)

Revaccination Subcohorts: Number of Participants With Unsolicited AEs 28 Days After Re-vaccination up to 1, 2 and 3 Years

Time frame: 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)

Revaccination Subcohorts: Number of Participants With Adverse Events of Special Interests (AESI)

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.

Time frame: 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)

Main Cohorts:Number of Participants With Serious Adverse Events (SAEs)

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.

Time frame: From Day 1 up to Day 1095

Revaccination Subcohorts: Number of Participants With Serious Adverse Events (SAEs)

Main Cohorts: Geometric Mean Titers (GMTs) of Prefusion F-protein (Pre-F) A Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)

GMTs of preF-A antibodies after the administration of Ad26.RSV.preF-based vaccine as assessed by ELISA were reported.

Time frame: Days 15, 85, 169, 365, 533