Study Description

RSV is an important cause of serious respiratory infections in adults aged 60 years and older, immunocompromised individuals, and those with underlying chronic cardiopulmonary conditions. The current study assess the safety and immunogenicity of the RSV vaccine in adults 18 to 59 years of age, including those who are at risk for severe RSV disease. The study comprises screening (pre-vaccination) and vaccination for each participant on Day 1, and a 6- month safety and immunogenicity follow-up period. The study duration will be up to 6 months per participant. Assessments like immunogenicity (such as humoral and cellular immune responses), safety (such as monitoring of AEs, physical examinations, and vital signs) and reactogenicity will be performed in this study.

Condition or Disease	Intervention/Treatment
Respiratory Syncytial Virus Infection Prevention	Biological: Ad26.RSV.preF-based Vaccine Other: Placebo

Study Design

Study Type	Interventional
Actual Enrollment	1124 participants
Design Allocation	Randomized
Interventional Model	Parallel Assignment
Masking	Double
Primary Purpose	Prevention
Official Title	A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Evaluate the Safety and Immunogenicity of an Ad26.RSV.preF-based Vaccine in Adults Aged 18 to 59 Years, Including Those at High-risk for Severe RSV
Study Start Date	September 29, 2021
Actual Primary Completion Date	August 12, 2022
Actual Study Completion Date	August 12, 2022

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
Cohort (C)1 Group (G)1: Healthy Adults, 18-59 Years (Respiratory Syncytial Virus [RSV] vaccine) Participants will receive a single intramuscular (IM) injection of study vaccine on Day 1.	Biological: Ad26.RSV.preF-based Vaccine Participants will receive a single IM injection of an RSV vaccine.
C1 G2: Healthy Adults, 18-59 Years (Placebo) Participants will receive a single IM injection of matching placebo on Day 1.	Other: Placebo
C2 G3: High Risk Adult, 18-59 Years (RSV Vaccine) Participants will receive a single IM injection of study vaccine on Day 1.	Biological: Ad26.RSV.preF-based Vaccine Participants will receive a single IM injection of an RSV vaccine.
C2 G4: High Risk Adult, 18-59 Years (Placebo) Participants will receive a single IM injection of matching placebo on Day 1.	Other: Placebo
C3 G5: Adults, 65 Years and Older (RSV Vaccine) Participants will receive a single IM injection of study vaccine on Day 1.	Biological: Ad26.RSV.preF-based Vaccine Participants will receive a single IM injection of an RSV vaccine.
C3 G6: Adults, 65 Years and Older (Placebo) Participants will receive a single IM injection of matching placebo on Day 1.	Other: Placebo

Outcome Measures

Primary Outcome Measures

1. Cohorts 1 and 2: Number of Participants With Solicited Local Adverse Events (AEs) [7 days after vaccination on Day 1 (Day 8)]
   Number of participants with solicited local AEs at 7 days post-vaccination in Cohorts 1 and 2 were reported. 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. Solicited local AEs were predefined local events (at the injection site: erythema, pain/tenderness and swelling) that were by definition considered as related to the study vaccine and collected within 7 days after vaccination.
2. Cohorts 1 and 2: Number of Participants With Solicited Systemic AEs [7 days after vaccination on Day 1 (Day 8)]
   Number of participants with solicited systemic AEs at 7 days post-vaccination in Cohorts 1 and 2 were reported. 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. Solicited systemic AEs including pyrexia, headache, fatigue, myalgia and nausea were collected within 7 days after vaccination.
3. Cohorts 1 and 2: Number of Participants With Unsolicited AEs [28 days after vaccination on Day 1 (Day 29)]
   Number of participants with unsolicited AEs post-vaccination in Cohorts 1 and 2 were reported. An AE was defined as any untoward medical occurrence in a participant participating in a clinical study that did not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs were defined as all AEs for which the participant was not specifically questioned in the participant diary.
4. Cohorts 1, 2, and 3: Number of Participants With Serious Adverse Events (SAEs) [6 months after vaccination on Day 1 (Day 183)]
   Number of participants with SAEs post-vaccination were reported. An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. SAE was defined as any AE that resulted in: death, persistent or significant disability/incapacity, required inpatient hospitalization or prolongation of existing hospitalization, was life-threatening experience, was a congenital anomaly/birth defect and would jeopardize participant and/or required medical or surgical intervention to prevent one of the outcomes listed above.
5. Cohorts 1, 2, and 3: Number of Participants With Adverse Events of Special Interest (AESI) [6 months after vaccination on Day 1 (Day 183)]
   Number of participants with AESI post-vaccination were reported. AESIs were significant AEs that were judged to be of special interest because of clinical importance, known or suspected class effects, or based on nonclinical signals. Thrombosis with thrombocytopenia syndrome (TTS) was considered as an AESI.
6. Cohorts 1 (Group 1), 2 (Group 3), and 3 (Group 5): Respiratory Syncytial Virus (RSV) A2 Strain Neutralizing Antibody Titers [14 days after vaccination on Day 1 (Day 15)]
   RSV A2 strain neutralizing antibody titers of the vaccine-induced immune response was assessed through virus neutralization assay and were expressed as 50% inhibitory concentration (IC50) units.
7. Cohorts 1 (Group 1), 2 (Group 3), and 3 (Group 5): Percentage of Participants With Seroresponse as Assessed by Virus Neutralizing Assay (VNA-A2) [14 days after vaccination on Day 1 (Day 15)]
   Percentage of participants with seroresponse as assessed by VNA-A2 strain were reported. Seroresponse was defined as a 4-fold increase from baseline in Day 15 VNA A2 antibody titers.

Secondary Outcome Measures

1. Cohorts 1, 2, and 3: Geomteric Mean Titers (GMTs) of RSV Fusion Protein (F-protein) Antibodies as Assessed by Enzyme-linked Immunosorbent Assay (ELISA)- Pre-Fusion [14 days after vaccination on Day 1 (Day 15)]
   GMTs of RSV Fusion Protein (PreF) antibodies as assessed by ELISA-Pre-Fusion at Day 15 were reported.

Eligibility Criteria

Ages Eligible for Study	18 Years and Older (Adult, Older Adult)
Sexes Eligible for Study	All
Accepts Healthy Volunteers	Yes
Inclusion Criteria	Participants must be of a) non child bearing potential or b) of child bearing potential and practicing an acceptable and effective of contraception All participants of childbearing potential must: have a negative highly sensitive urine beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening; and have a negative highly sensitive urine beta-hCG pregnancy test immediately prior to each study vaccination (if screening and vaccination are not performed on the same day) Cohorts 1 and 2 Participant is aged 18 to 59 years (inclusive) on the day of signing the informed consent form (ICF) and expected to be available for the duration of the study Cohort 2 Has an existing chronic heart or lung condition, without hospitalizations or major medication class change (that is, new or stopped medications) within 30 days prior to screening, meeting the following criteria; a) cardiac disease: at least Class II symptoms per New York Heart Association classification or similar guidelines according to local practice, b) pulmonary disease: activity-restricting symptoms or use of long-term medications Cohort 3 Participant is aged 65 years or older on the day of signing the ICF and expected to be available for the duration of the study Participant may have underlying illnesses such as hypertension, congestive heart failure, chronic obstructive pulmonary disease (COPD), type 2 diabetes, hyperlipoproteinemia, or hypothyroidism, as long as their symptoms and signs are stable at the time of vaccination, and these conditions receive routine follow-up by the participant's healthcare provider
Exclusion Criteria	Known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients (including specifically the excipients of the study vaccine) Abnormal function of immune system due to a clinical condition or treatment History of thrombosis with thrombocytopenia syndrome (TTS) or heparin-induced thrombocytopenia and thrombosis (HITT). Participant received or plans to receive: (a) licensed live attenuated vaccines - within 28 days before or after planned administration of study vaccine; and (b) other licensed (not live) vaccines - within 14 days before or after planned administration of study vaccine Received an respiratory syncytial virus (RSV) vaccine in a previous RSV vaccine study History of acute polyneuropathy (example, Guillain-Barre syndrome) or chronic idiopathic demyelinating polyneuropathy

Contacts and Locations

Sponsors and Collaborators	Janssen Vaccines & Prevention B.V.
Locations	Alliance for Multispeciality Research | Coral Gables, Florida, United States, 33134 Research Institute of South Florida Inc | Miami, Florida, United States, 33173 Heartland Research Associates, an AMR Company | El Dorado, Kansas, United States, 67042 AMR New Orleans, Formerly New Orleans Center for Clinical Research - New Orleans, an AMR company | New Orleans, Louisiana, United States, 70119 Meridian Clinical Research, LLC | Rockville, Maryland, United States, 20854 Tekton Research Inc. | Yukon, Oklahoma, United States, 73099 Alliance for Multispeciality Research | Knoxville, Tennessee, United States, 37909 Anima | Alken, Belgium, 3570 C.H.U. St Pierre / Maladies Infectieuses | Bruxelles, Belgium, Private Practice RESPISOM Namur | Namur, Belgium, 5101 Emovis GmbH | Berlin, Germany, 10629 Klinische Forschung Berlin GbR | Berlin, Germany, 10787 Klinische Forschung Dresden GmbH | Dresden, Germany, 01069 Clinical Research HamburggmbH | Hamburg, Germany, 22143 Zentrum fuer klinische Forschung | Koeln, Germany, 51069 SIBAmed GmbH & Co. KG | Leipzig, Germany, 04103 Klinische Forschung Schwerin GmbH | Schwerin, Germany, 19055 Hosp. Reina Sofia | Córdoba, Spain, 14004 Hosp. Virgen de La Victoria | Málaga, Spain, 29010 ProbarE i Lund AB | Lund, Sweden, 22222 ClinSmart Sweden AB | Solna, Sweden, 171 64 ProbarE i Stockholm AB | Stockholm, Sweden, 113 29 Studieenheten Akademiskt Specialistcentrum Stockholm | Stockholm, Sweden, 11361
Investigators

Study Documents (Full Text)

• Documents Provided by Janssen Vaccines & Prevention B.V.: Study Protocol November 30, 2021
• Documents Provided by Janssen Vaccines & Prevention B.V.: Statistical Analysis Plan July 11, 2022

More Information

Additional Relevant MeSH Terms

• Infections
• Respiratory Syncytial Virus Infections
• Virus Diseases
• Pneumovirus Infections
• Paramyxoviridae Infections
• Mononegavirales Infections
• RNA Virus Infections