RiiQ™ application in Janssen CYPRESS trial supports understanding of vaccine effectiveness
In November 2020, the European Medicines Agency's Committee for Medicinal Products for Human Use designated Janssen's RSV adult vaccine candidate as eligible for the priority medicines (PRIME) scheme based on promising clinical data and an unmet need for a prophylactic option to prevent RSV in older adults.
Presented at the 8th ESWI Influenza conference
An Ad26.RSV.preF-based Vaccine is Effective for Prevention of RSV-mediated Lower Respiratory Tract Disease and Reduces Symptom Severity in Vaccine Recipients With RSV Infection: A Phase 2b Study in Older Adults
BACKGROUND
Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease (LRTD) in older adults. Currently, no licensed vaccine for the prevention of RSV is available. Ad26.RSV.preF is a recombinant, replication-incompetent, human adenovirus serotype 26 (Ad26) vectored RSV vaccine, encoding a conformation-stabilized prefusion RSV F (preF) protein. In this Phase 2b proof-of-concept trial, we report the vaccine efficacy of Ad26.RSV-preF in combination with recombinant RSV preF protein for the prevention of RSV-mediated LRTD in adults aged ≥65 years.
METHODS
CYPRESS (NCT03982199) is a randomized, double-blind, placebo-controlled, Phase 2b trial. Adults aged ≥65 years were randomized 1:1 prior to the RSV season to receive an Ad26.RSV.preF-based regimen or placebo. The primary endpoint was the first occurrence of RT-PCR-confirmed RSV-mediated LRTD during the first RSV season according to any of 3 case definitions: (1) ≥3 symptoms of lower respiratory tract infection (LRTI), (2) ≥2 symptoms of LRTI, or (3) ≥2 symptoms of LRTI or ≥1 symptom of LRTI with ≥1 systemic symptom. The secondary endpoint was the first occurrence of any RT-PCR-confirmed RSV-mediated acute respiratory infection (ARI). ARI symptoms were collected using an RSV-specific patient-reported Respiratory Infection Intensity and Impact Questionnaire (RiiQ; daily during the ARI episode) and/or by clinician assessment (ARI Day 3, 4, or 5). An independent clinical evaluation committee (CEC) assessed participant- and clinician-reported data for participants with RSV-positive ARIs to determine the location (upper or lower respiratory tract) and severity of the ARI. RiiQ scores and time to return to usual health (Patient Global Impression Return to Usual Health question) were compared between participants with RSV ARIs in the vaccine versus placebo groups.
RESULTS
A total of 5782 participants (2891 in each study group) received study treatment (92.5% white, 57.7% female, median age 71 years). Vaccine efficacy for LRTD case definitions 1, 2, and 3 was 80% (94.2% CI, 52.2-92.9%), 75% (50.1-88.5%), and 69.8% (43.7-84.7%), respectively (all P values <0.001). Efficacy was 69.8% (95% CI: 42.7-85.1%) for the first occurrence of any RSV-mediated ARI and 67.9% (26.6-87.5%) for CEC-assessed RSV-positive moderate/severe LRTD. Median area under the curve (AUC) for total RiiQ scores was lower (indicating less severe symptoms) in participants in the vaccine group with RSV ARI (n=13; median AUC [Q1; Q3], 39 [11; 74]) than in the placebo group (n=41; 128 [58; 242]). Time to return to usual health after RSV ARI was faster in the vaccine group than in the placebo group (median, 19 vs 30 days; HR [95% CI], 2.812 [1.006-7.86]).
CONCLUSIONS
Ad26.RSV.preF-based vaccine was highly effective for the prevention of RSV-mediated LRTD during the first RSV season in adults aged ≥65 years. Vaccinated participants who experienced RSV-mediated ARIs had milder symptoms and faster return to usual health than the placebo group.