C3671023 Substudy A (NCT05842967)(MONeT Study) is a phase 3, randomized, double-blind, placebo-controlled trial assessing the safety and immunogenicity of Pfizer’s RSVpreF vaccine in high-risk adults aged 18-59 with chronic medical conditions, such as pulmonary, cardiovascular, hepatic, renal, and metabolic disorders, including diabetes mellitus.

The study aims to show that the immune response in this younger high-risk group is non-inferior to that of adults aged 60 and older, as established in the pivotal phase 3 C3671013 study that demonstrated the vaccine’s efficacy against RSV Lower Respiratory Tract Illness (LRTI).

At IDWeek 2024, Elliot DeHaan, MD, director in vaccines clinical research and development at Pfizer, Inc, and lead clinician on this study, highlighted the significant findings, “What we found in this trial was that in adults 18 to 59 years of age with comorbid conditions such as chronic pulmonary conditions such as asthma, COPD, cardiovascular disease, and diabetes, these individuals had similar immune responses to adults 60 and older who were enrolled in the Renoir trial in which we demonstrated efficacy of that vaccine. This technique is called immuno-bridging, and what we can confer from that immuno-bridging result is that we expect the immune response to be the same in these individuals.”

Participants were randomized in a 2:1 ratio to receive either one dose of RSVpreF (453 participants) or a placebo (225 participants). Serum samples were collected before and one month after vaccination and tested alongside samples from approximately 400 RSVpreF recipients in the C3671013 study. Reactogenicity events were monitored for seven days post-vaccination, while adverse events (AEs) were tracked for one month. Adverse events of special interest (AESIs), newly diagnosed chronic medical conditions (NDCMCs), and serious AEs were recorded throughout the study. Non-inferiority would be confirmed if the lower bounds of the 95% confidence interval (CI) for the adjusted Geometric Mean Ratio (GMR) of neutralizing titers (NTs) exceeded 0.667, and the lower bounds of the 95% CI for seroresponse rate differences exceeded -10% for RSV A and B.

DeHaan discussed the safety profile of the vaccine observed in the trial, particularly for the high-risk population, “the most common solicited local reaction in our sub-study A was pain at the injection site, reported by around 35% of vaccine recipients. The two most common systemic solicited events were fatigue and headache. These results were very similar to those in other trials, indicating consistent tolerability and safety.”

Proportions of participants experiencing local reactions were higher in the RSVpreF group, while systemic events were similar across both groups. Rates of participants reporting any AEs were comparable between the RSVpreF and placebo groups during the month following vaccination and throughout the study.

One month after vaccination, neutralizing titers (NTs) for RSV A and B in high-risk adults aged 18-59 were non-inferior to those in adults aged 60 and older, meeting the criteria for non-inferiority in seroresponse rates. RSVpreF was well-tolerated with no significant safety concerns and demonstrated immunobridging to efficacy in the younger high-risk group compared to older adults. These findings support the use of RSVpreF for preventing RSV lower respiratory tract illness (LRTI) in adults aged 18-59 with high-risk conditions.

DeHaan discussed the implications of these results for future RSV vaccination efforts, especially considering the rising burden of RSV in adults, “we are aiming for approval in adults aged 18 to 59 with comorbid conditions. If granted, this would be the broadest indication for an RSV vaccine in this population. We’re hopeful for this and expect a decision in the fourth quarter of this year.”

Reference

DeHaan, Davis M, Towner W, et, al. Immunobridging Demonstrating Effectiveness of the Bivalent Respiratory Syncytial Virus (RSV) Prefusion F Subunit Vaccine in Adults 18-59 Years of Age at High Risk of Severe RSV Disease in a Phase 3 Trial: The C3671023 MONeT Study Results. Poster #596 was presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.