A Study to Evaluate a Range of Dose Levels of an Adenovirus Serotype 26 (Ad26.RSV.preF)-Based Vaccine in Older Adults

Study Overview
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Brief Summary
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The purpose of this study is to explore the dose-response relationship of immune responses induced by different dose levels of an Ad26.RSV.preF based vaccine (Cohort 1) and to assess the safety and reactogenicity of different dose levels of the Ad26.RSV.preF-based vaccine (Cohorts 2 and 3).

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 2a Study to Evaluate a Range of Dose Levels of an Ad26.RSV.preF-based Vaccine in Adults Aged 60 Years and Older

Conditions
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Healthy

Intervention / Treatment
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* Biological: RSV Vaccine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In the investigator's clinical judgment, participants must be either in good or stable health. Participants may have underlying illnesses such as hypertension, type 2 diabetes mellitus, hyperlipoproteinemia, or hypothyroidism, as long as their signs and symptoms are stable and medically controlled in the judgment of the investigator. Participants will be included on the basis of medical history and of physical examination and vital signs performed at screening (all cohorts), and of physical examination and/or vital signs performed prevaccination on Day 1 (Cohorts 2 and 3) A woman must be postmenopausal (defined as no menses for 12 months without an alternative medical cause) and not intending to conceive by any methods Agree to not donate blood from the time of vaccination until 3 months after vaccination Have a body mass index (BMI) less than (<) 40 kilogram per meter square (kg/m^2) Be willing to provide verifiable identification and have means to be contacted and to contact the investigator during the study Exclusion Criteria: Has a contraindication to intramuscular injection (IM) injections and blood draws (example, bleeding disorders) 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) History of chronic urticaria (recurrent hives), eczema, or atopic dermatitis Has hepatitis B or C infection, including history of treated hepatitis C infection Received an active RSV vaccine in a previous RSV vaccine study or an Ad26-vectored vaccine at any time prior to randomization

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Group 1: RSV Vaccine<br>Participants will receive a single intramuscular (IM) injection of an Ad26-based RSV vaccine on Day 1. | Biological: RSV Vaccine<br>* Participants will receive a single IM injection of an Ad26-based RSV vaccine on Day 1.<br>|
| Experimental: Cohort 1 Group 2: RSV Vaccine<br>Participants will receive a single IM injection of an Ad26-based RSV vaccine (low dose 1) on Day 1. | Biological: RSV Vaccine<br>* Participants will receive a single IM injection of an Ad26-based RSV vaccine on Day 1.<br>|
| Experimental: Cohort 1 Group 3: RSV Vaccine<br>Participants will receive a single IM injection of an Ad26-based RSV vaccine (low dose 2) on Day 1. | Biological: RSV Vaccine<br>* Participants will receive a single IM injection of an Ad26-based RSV vaccine on Day 1.<br>|
| Experimental: Cohort 1 Group 4: RSV Vaccine<br>Participants will receive a single IM injection of an Ad26-based RSV vaccine (low dose 3) on Day 1. | Biological: RSV Vaccine<br>* Participants will receive a single IM injection of an Ad26-based RSV vaccine on Day 1.<br>|
| Placebo Comparator: Cohort 1 Group 5: Placebo<br>Participants will receive IM injection of placebo on Day 1. | Other: Placebo<br>* Participants will receive a single IM injection of placebo on Day 1.<br>|
| Experimental: Cohort 2 Group 6: RSV Vaccine<br>Participants will receive a single IM injection of an Ad26-based RSV vaccine on Day 1. | Biological: RSV Vaccine<br>* Participants will receive a single IM injection of an Ad26-based RSV vaccine on Day 1.<br>|
| Experimental: Cohort 2 Group 7: RSV Vaccine<br>Participants will receive a single IM injection of an Ad26-based RSV vaccine (high dose 1) on Day 1. | Biological: RSV Vaccine<br>* Participants will receive a single IM injection of an Ad26-based RSV vaccine on Day 1.<br>|
| Placebo Comparator: Cohort 2 Group 8: Placebo<br>Participants will receive IM injection of placebo on Day 1. | Other: Placebo<br>* Participants will receive a single IM injection of placebo on Day 1.<br>|
| Experimental: Cohort 3 Group 9: RSV Vaccine<br>Participants will receive a single IM injection of an Ad26-based RSV vaccine on Day 1. | Biological: RSV Vaccine<br>* Participants will receive a single IM injection of an Ad26-based RSV vaccine on Day 1.<br>|
| Experimental: Cohort 3 Group 10: RSV Vaccine<br>Participants will receive a single IM injection of an Ad26-based RSV vaccine (high dose 2) on Day 1. | Biological: RSV Vaccine<br>* Participants will receive a single IM injection of an Ad26-based RSV vaccine on Day 1.<br>|
| Experimental: Cohort 3 Group 11: Placebo<br>Participants will receive IM injection of placebo on Day 1. | Other: Placebo<br>* Participants will receive a single IM injection of placebo on Day 1.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: Geometric Mean Antibody Titers to Respiratory Syncytial Virus (RSV) Prefusion Conformation-stabilized F (preF) Protein Using preF Enzyme-linked Immunosorbent Assay (ELISA) at 14 Days After Vaccination | Geometric mean antibody titers (ELISA units per liter [EU/L]) to RSV preF protein using preF ELISA at 14 days after vaccination were reported. | 14 days after vaccination on Day 1 (Day 15) | 
| Cohorts 2 and 3: Number of Participants With Solicited Local Adverse Events (AEs) Until 7 Days After Vaccination on Day 1 | Number of participants with solicited local AEs until 7 days after vaccination on Day 1 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. Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their e-diary until 7 days after vaccination on Day 1 (day of vaccination and the subsequent 7 days). Solicited local AEs included: injection site pain/tenderness, erythema and swelling at the vaccination site. | Until 7 days after Vaccination on Day 1 (Day 8) | 
| Cohorts 2 and 3: Number of Participants With Solicited Systemic Adverse Events (AEs) Until 7 Days After Vaccination on Day 1 | Number of participants with solicited systemic AEs until 7 days after vaccination on Day 1 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. Participants were instructed on how to note signs and symptoms in their diary on a daily basis until 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic AEs included fatigue, headache, myalgia, nausea and fever (body temperature greater than or equal to [>=] 38 degree celsius). | Until 7 days after Vaccination on Day 1 (Day 8) | 
| Cohorts 2 and 3: Number of Participants With Unsolicited AEs Until 28 Days After Vaccination on Day 1 | Unsolicited AEs were all AEs for which the participants were not specifically questioned in the participant diary. 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. Unsolicited AEs included chills, injection site erythema, injection site pruritus Et cetera (etc). | Until 28 days after Vaccination on Day 1 (Day 29) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: Geometric Mean Antibody Titers to RSV preF Protein Using preF ELISA at 3 and 6 Months After Vaccination on Day 1 | Geometric mean antibody titers (EU/L) to RSV preF protein using preF ELISA at 3 and 6 months after vaccination on Day 1 were reported. | At 3 and 6 months after vaccination on Day 1 | 
| Cohort 1: Respiratory Syncytial Virus (RSV) A2 Strain Neutralizing Antibody Titers at 14 Days and 3 and 6 Months After Vaccination on Day 1 | RSV A2 strain neutralizing antibody titers at 14 days and 3 and 6 months after vaccination on Day 1 were reported. RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay. Data were expressed as 50% inhibitory concentration (IC50) units. | At 14 days and 3 and 6 months after vaccination on Day 1 | 
| Cohort 1: T-cell Interferon (IFN) Gamma Responses to Respiratory Syncytial Virus (RSV) F Protein Peptides | T-cell IFN gamma responses to RSV F protein specific peptides at 14 days and 3 and 6 months after vaccination as measured by enzyme-linked immunospot (ELISpot) assay were reported. RSV F 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). | At 14 days and 3 and 6 months after vaccination on Day 1 | 
| Cohort 1: Number of Participants With Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product. | Baseline (Day1) up to 6 months | 
| Cohort 1: Number of Participants With Solicited Local Adverse Events (AEs) Until 7 Days After Vaccination on Day 1 | Number of participants with solicited local AEs until 7 days after vaccination on Day 1 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. Solicited local AEs were pre-defined local (at the injection site) AEs for which participants were specifically questioned and which were noted by participants in their e-diary until 7 days after vaccination on Day 1 (day of vaccination and the subsequent 7 days). Solicited local AEs included: injection site pain/tenderness, erythema and swelling at the vaccination site. | Until 7 days after vaccination on Day 1 (Day 8) | 
| Cohort 1: Number of Participants With Solicited Systemic Adverse Events (AEs) Until 7 Days After Vaccination on Day 1 | Number of participants with solicited systemic AEs until 7 days after vaccination on Day 1 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. Participants were instructed on how to note signs and symptoms in their diary on a daily basis until 7 days post-vaccination (Day of vaccination and the subsequent 7 days) for solicited systemic AEs. Solicited systemic AEs included fatigue, headache, myalgia, nausea and fever (body temperature >=38 degree celsius). | Until 7 days after vaccination on Day 1 (Day 8) | 
| Cohort 1: Number of Participants With Unsolicited AEs Until 28 Days After Vaccination on Day 1 | Unsolicited AEs were all AEs for which the participants were not specifically questioned in the participant diary. Unsolicited AEs included chills, injection site erythema, injection site pruritus Et cetera (etc). | Until 28 days after vaccination on Day 1 (Day 29) | 
| Cohort 2 and 3: Geometric Mean Antibody Titers to RSV preF Protein Using preF ELISA at 14 Days and 3 and 6 Months After Vaccination on Day 1 | Geometric mean antibody titers (EU/L) to RSV preF protein using preF ELISA at 14 days and 3 and 6 months after vaccination on Day 1 were reported. | At 14 days and 3 and 6 months after vaccination on Day 1 | 
| Cohort 2 and 3: Respiratory Syncytial Virus (RSV) A2 Strain Neutralizing Antibody Titers at 14 Days and 3 Months After Vaccination on Day 1 | RSV A2 neutralizing antibody titers at 14 days and 3 months after vaccination on Day 1 were reported. RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay. Data were expressed as 50% IC50 units. | At 14 days and 3 months after vaccination on Day 1 | 
| Cohort 2 and 3: T-cell Interferon (IFN) Gamma Responses to Respiratory Syncytial Virus (RSV) F Protein Peptides at 14 Days and 3 and 6 Months After Vaccination on Day 1 | T-cell IFN gamma responses to RSV F protein specific peptides at 14 days and 3 and 6 months after vaccination as measured by ELISpot assay were reported. RSV F 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). | At 14 days and 3 and 6 months after vaccination on Day 1 | 
| Cohort 2 and 3: Number of Participants With Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product. | Baseline (Day1 ) up to 6 months |