VAC18193 / J&J - LARVOL DELTA

Phase 3 study of an Ad26.RSV.preF/RSV preF protein vaccine to evaluate the prevention efficacy of RSV-mediated lower tract disease, immunogenicity and safety in Japanese adults. (PubMed, Respir Investig) - P3 | "Although vaccine efficacy could not be concluded, it was immunogenic with acceptable safety profile in both Japanese younger and older adult population."

Clinical • Journal • P3 data • Respiratory Diseases • Respiratory Syncytial Virus Infections

A Study to Evaluate the Safety and Immunogenicity of Seasonal Influenza Vaccine and an Adenovirus Serotype 26- Based Vaccine Encoding for the Respiratory Syncytial Virus Pre-fusion F Protein (Ad26.RSV.preF), With and Without Co-administration, in Adults Aged 60 Years and Older in Stable Health (clinicaltrials.gov) - P2 | N=180 | Completed | Sponsor: Janssen Vaccines & Prevention B.V. | Phase classification: P2a ➔ P2

Phase classification • Infectious Disease • Influenza • Respiratory Diseases • Respiratory Syncytial Virus Infections

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 (clinicaltrials.gov) - P2 | N=64 | Completed | Sponsor: Janssen Vaccines & Prevention B.V. | Phase classification: P2a ➔ P2

Phase classification • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

A Study Evaluating the Immunogenicity of Different Clinical Trial Materials of Ad26.RSV.preF- Based Vaccine in Adults Aged 60 - 75 Years Old (clinicaltrials.gov) - P3 | N=250 | Completed | Sponsor: Janssen Vaccines & Prevention B.V. | Phase classification: P2b ➔ P3

Phase classification • Respiratory Diseases • Respiratory Syncytial Virus Infections

Ad26.RSV.preF completely protects calves from severe respiratory disease induced by bovine RSV challenge. (PubMed, NPJ Vaccines) - "In contrast, all Ad26.RSV.preF immunized calves completed the study with only mild clinical symptoms, strongly and significantly diminished viral loads in nasopharynx and lungs, and only minimal lung pathology. Thus, Ad26.RSV.preF is immunogenic in young calves and efficacious in a stringent heterologous bRSV challenge model, demonstrating induction of broadly protective immunity against severe disease."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Immunogenicity and safety of different dose levels of Ad26.RSV.preF/RSV preF protein vaccine in adults aged 60 years and older: A randomized, double-blind, placebo-controlled, phase 2a study. (PubMed, Vaccine) - P2 | "Results of this dose-ranging study may be used to inform the refinement of Ad26.RSV.preF drug product release and stability specifications."

Clinical • Journal • P2a data • Geriatric Disorders • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNG

A Phase 1/2a Study Evaluating Safety and Immunogenicity of Ad26.RSV.preF in RSV-seronegative Toddlers Aged 12-24 Months. (PubMed, Open Forum Infect Dis) - P1/2 | "In this randomized, observer-blinded, placebo-controlled, phase 1/2a study (NCT03606512; https://www.clinicaltrials.gov/ct2/show/NCT03606512), RSV-seronegative toddlers aged 12-24 months received Ad26.RSV.preF (2.5 × 1010 viral particles) or placebo on days 1, 29, and 57 (a meningococcal vaccine [Nimenrix] could substitute for day 57 placebo). At the final season 1 study visit, most Ad26.RSV.preF recipients had ≥2-fold increases from baseline in RSV-A2 neutralizing, RSV A and B preF binding, and RSV postF antibodies. Ad26.RSV.preF was well tolerated and immunogenic in RSV-seronegative toddlers."

Journal • P1/2 data • Infectious Disease • Meningococcal Infections • Otorhinolaryngology • Pediatrics • Respiratory Diseases • Respiratory Syncytial Virus Infections

Immunogenicity, safety and reactogenicity of Ad26.RSV.preF/RSV preF protein vaccine in adults aged 60 to 75 years: A comparison of phase 2b and phase 3 clinical trial material. (PubMed, Hum Vaccin Immunother) - "The safety profile in terms of solicited AEs, unsolicited AEs, or SAEs was in general similar between the phase 3 CTM and phase 2b CTM groups, and solicited AEs were mostly mild to moderate in intensity. No related SAEs were reported, and no safety concerns were identified."

Clinical • Journal • P2b data • P3 data • Respiratory Diseases • Respiratory Syncytial Virus Infections

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Single Vaccination of Ad26.RSV.preF-Based Regimen in Japanese Adults Aged 60 Years and Older. (PubMed, Influenza Other Respir Viruses) - P1 | "A single dose of Ad26.RSV.preF/RSV preF protein vaccine had an acceptable safety and tolerability profile and induced RSV-specific humoral immunity in Japanese healthy adults."

Clinical • Journal • P1 data • P1 data • Respiratory Diseases • Respiratory Syncytial Virus Infections

Efficacy of Respiratory Syncytial Virus Vaccination to Prevent Lower Respiratory Tract Illness in Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. (PubMed, Vaccines (Basel)) - "Our analysis included five RCTs on five RSV vaccines (RSVpreF, RSVPreF3, Ad26.RSV.preF, MEDI7510, and mRNA-1345). In conclusion, adult RSV vaccination was quite effective in preventing LRTD in older adults, but the overall efficacy rapidly decreased in the second season after the delivery of the vaccine. Because of the heterogenous design of the parent studies, further analyses are required before tailoring specific public health interventions."

Journal • Retrospective data • Review • Geriatric Disorders • Infectious Disease • Pneumonia • Respiratory Diseases • Respiratory Syncytial Virus Infections

Long-term efficacy and immunogenicity of Ad26.RSV.preF-RSV preF protein vaccine (CYPRESS): a randomised, double-blind, placebo-controlled, phase 2b study. (PubMed, Lancet Infect Dis) - P2 | "Ad26.RSV.preF-RSV preF protein maintained high efficacy against RSV LRTD in older adults across three RSV seasons."

Journal • P2b data • Respiratory Diseases • Respiratory Syncytial Virus Infections

Immunogenicity and safety of Ad26.RSV.preF/RSV preF protein vaccine at predicted intermediate- and end-of-shelf-life as an evaluation of potency throughout shelf life. (PubMed, Hum Vaccin Immunother) - "The study provided evidence of sustained immunogenicity and safety over the intended shelf-life of the Ad26.RSV.pref/RSV preF protein vaccine. The three vaccine lots had acceptable safety profiles."

Clinical • Journal • P1 data • Respiratory Diseases • Respiratory Syncytial Virus Infections

CYPRESS: 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 (clinicaltrials.gov) - P2 | N=5815 | Terminated | Sponsor: Janssen Vaccines & Prevention B.V. | Phase classification: P2b ➔ P2 | Completed ➔ Terminated; The study was terminated early by the sponsor due to strategic reprioritization reasons.

Phase classification • Trial termination • Respiratory Diseases • Respiratory Syncytial Virus Infections

A Study to Evaluate a Range of Dose Levels of an Adenovirus Serotype 26 (Ad26.RSV.preF)-Based Vaccine in Older Adults (clinicaltrials.gov) - P2 | N=459 | Completed | Sponsor: Janssen Vaccines & Prevention B.V. | Phase classification: P2a ➔ P2

Phase classification • Respiratory Syncytial Virus Infections

Concomitant Administration of Ad26.RSV.preF/RSV preF Protein Vaccine and High-dose Influenza Vaccine in Adults 65 Years and Older: a Noninferiority Trial. (PubMed, J Infect Dis) - "Coadministration of Ad26.RSV.preF/RSV preF protein and Fluzone-HD® showed an acceptable safety profile and did not hamper the immunogenicity of either vaccine, thus supporting that both vaccines can be concomitantly administered in adults ≥65 years old."

Head-to-Head • Journal • Infectious Disease • Influenza • Respiratory Diseases • Respiratory Syncytial Virus Infections

Vaccine-induced antibody Fc-effector functions in humans immunized with a combination Ad26.RSV.preF/RSV preF protein vaccine. (PubMed, J Virol) - "In this work, we show that the investigational Ad26.RSV.preF/RSV preF protein vaccine induced Fc-effector functional immune responses in adults aged ≥60 years who were enrolled in a phase 1/2a regimen selection study of Ad26.RSV.preF/RSV preF protein. These results demonstrate the breadth of the immune responses induced by the Ad26.RSV.preF/RSV preF protein vaccine."

Journal • Geriatric Disorders • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

EVERGREEN: A Study of an Adenovirus Serotype 26 Pre-fusion Conformation-stabilized F Protein (Ad26. RSV. preF) Based Respiratory Syncytial Virus (RSV) Vaccine in the Prevention of Lower Respiratory Tract Disease in Adults Aged 60 Years and Older (clinicaltrials.gov) - P3 | N=25236 | Completed | Sponsor: Janssen Vaccines & Prevention B.V. | Active, not recruiting ➔ Completed

Trial completion • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNG

EVERGREEN: A Study of an Adenovirus Serotype 26 Pre-fusion Conformation-stabilized F Protein (Ad26. RSV. preF) Based Respiratory Syncytial Virus (RSV) Vaccine in the Prevention of Lower Respiratory Tract Disease in Adults Aged 60 Years and Older (clinicaltrials.gov) - P3 | N=25236 | Active, not recruiting | Sponsor: Janssen Vaccines & Prevention B.V. | Trial completion date: Nov 2024 ➔ Oct 2023 | Trial primary completion date: Oct 2024 ➔ Jul 2023

Trial completion date • Trial primary completion date • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNG

CYPRESS: 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 (clinicaltrials.gov) - P2b | N=5815 | Completed | Sponsor: Janssen Vaccines & Prevention B.V. | Active, not recruiting ➔ Completed | Trial completion date: May 2024 ➔ May 2023

Trial completion • Trial completion date • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNG

Safety, Immunogenicity, and Regimen Selection of Ad26.RSV.preF-based Vaccine Combinations: A Randomized, Double-blind, Placebo-Controlled, Phase 1/2a Study. (PubMed, J Infect Dis) - P1/2 | "All Ad26.RSV.preF-based regimens were well tolerated. A combination regimen comprising both Ad26.RSV.preF, which elicits strong humoral and cellular responses, and RSV preF protein, which increases humoral responses, was selected for further development."

Clinical • Journal • P1/2 data • Respiratory Diseases • Respiratory Syncytial Virus Infections

EVERGREEN: A Study of an Adenovirus Serotype 26 Pre-fusion Conformation-stabilized F Protein (Ad26. RSV. preF) Based Respiratory Syncytial Virus (RSV) Vaccine in the Prevention of Lower Respiratory Tract Disease in Adults Aged 60 Years and Older (clinicaltrials.gov) - P3 | N=25253 | Active, not recruiting | Sponsor: Janssen Vaccines & Prevention B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNG

In older adults, an Ad26.RSV.preF-RSV preF protein vaccine reduced RSV-related lower respiratory tract disease. (PubMed, Ann Intern Med) - "2023;388:609-620. 36791161."

Journal • Respiratory Diseases • Respiratory Syncytial Virus Infections

A Study of Adenovirus Serotype 26.Respiratory Syncytial Virus.Pre-Fusion F (Ad26.RSV.preF)-Based Vaccine for Prevention of Respiratory Syncytial Virus (RSV) Mediated- Lower Respiratory Tract Disease (LRTD) in Japanese Participants (clinicaltrials.gov) - P3 | N=2192 | Terminated | Sponsor: Janssen Pharmaceutical K.K. | Recruiting ➔ Terminated; Terminated (Janssen made the strategic decision to discontinue the RSV3007 study. This decision is not based on any safety concerns.)

Trial termination • Respiratory Diseases • Respiratory Syncytial Virus Infections

Immunogenicity and safety of Ad26.RSV.preF/RSV preF protein vaccine co-administered with a seasonal influenza vaccine in older adults (ECCMID 2023) - No abstract available

Clinical • Infectious Disease • Influenza • Respiratory Diseases • Respiratory Syncytial Virus Infections

Combination Ad26.RSV.preF/preF protein vaccine induces superior protective immunity compared with individual vaccine components in preclinical models. (PubMed, NPJ Vaccines) - "Immunization with the combination elicited superior protection against RSV A2 challenge in cotton rats. These results demonstrate the advantage of a combination vaccine and support further clinical development."

Journal • Preclinical • Respiratory Diseases • Respiratory Syncytial Virus Infections