What are the randomized double-blind studies on the efficacy of Respiratory Syncytial Virus (RSV) vaccines?

Randomized Double-Blind Studies on RSV Vaccine Efficacy

The key randomized, double-blind, placebo-controlled trials demonstrating RSV vaccine efficacy include the AReSVi-006 study and a phase I/II trial for RSVPreF3 (Arexvy), and the RENOIR trial with a phase I/II trial for RSVpreF (Abrysvo), plus the ConquerRSV study and a phase I trial for the mRNA RSV vaccine (mRNA-1345). 1

RSVPreF3 (Arexvy) Trials

AReSVi-006 Study

• Phase 3, randomized, double-blind, placebo-controlled trial enrolling 24,966 participants aged ≥60 years 2
• Participants received either RSVPreF3 OA vaccine (n=12,467) or placebo (n=12,499) in a 1:1 ratio 2
• Primary efficacy results: 82.6% efficacy (96.95% CI: 57.9-94.1) against RT-PCR-confirmed RSV-associated lower respiratory tract disease over median 6.7 months follow-up 2
• Severe disease efficacy: 94.1% (95% CI: 62.4-99.9) against severe RSV-related lower respiratory tract disease 2
• Acute respiratory infection efficacy: 71.7% (95% CI: 56.2-82.3) against RSV-related acute respiratory infection 2
• Efficacy maintained across RSV subtypes: 84.6% for RSV-A and 80.9% for RSV-B 2
• Duration of protection: Efficacy maintained for at least three seasons, with cumulative efficacy of 62.9% (97.5% CI: 46.7-74.8%) over three seasons 1, 3

Phase I/II Trial for RSVPreF3

• Randomized, double-blind, placebo-controlled trial in participants ≥60 years old 1
• Participants received either the vaccine formulation used in the phase III trial or placebo 1

RSV OA-ADJ-18 Study

• Phase III, randomized, placebo-controlled trial evaluating immunogenicity in adults aged 50-59 years 1
• Demonstrated immunological noninferiority in adults aged 50-59 years compared with those aged ≥60 years 1
• Included participants both with and without chronic conditions (COPD, asthma, chronic cardiovascular disease, diabetes, CKD, chronic liver disease) 1

RSVpreF (Abrysvo) Trials

RENOIR Trial

• Phase 3, randomized, double-blind, placebo-controlled trial enrolling 34,284 participants aged ≥60 years 4
• Participants randomized 1:1 to receive RSVpreF vaccine 120 μg (n=17,215) or placebo (n=17,069) 4
• Primary efficacy results at interim analysis:
  • 66.7% efficacy (96.66% CI: 28.8-85.8) against RSV-associated lower respiratory tract illness with ≥2 symptoms 4
  • 85.7% efficacy (96.66% CI: 32.0-98.7) against RSV-associated lower respiratory tract illness with ≥3 symptoms 4
• Secondary endpoint: 62.1% efficacy (95% CI: 37.1-77.9) against RSV-associated acute respiratory illness 4
• Duration of protection: Efficacy maintained for at least two seasons, with 77.8% efficacy against RSV-LRTI with ≥3 symptoms at end of season 2 5
• Age-stratified efficacy over two seasons:
  • Ages 60-69: 57.5% (95% CI: 35.8-72.4) for ≥2 symptoms; 81.6% (95% CI: 58.2-93.1) for ≥3 symptoms 1
  • Ages 70-79: 62.5% (95% CI: 30.6-80.8) for ≥2 symptoms; 72.7% (95% CI: -3.2-95.1) for ≥3 symptoms 1
  • Ages ≥80: 54.5% (95% CI: -41.9-87.6) for ≥2 symptoms; 100% (95% CI: -9.1-100) for ≥3 symptoms 1

Phase I/II Trial for RSVpreF

• Randomized, double-blind, placebo-controlled trial in individuals ≥65 years old 1
• Participants received either the vaccine formulation used in the phase III trial or placebo 1

High-Risk Adults Trial (Ages 18-59)

• Phase 3, randomized trial (NCT05842967) in adults 18-59 years with high-risk conditions 6
• Participants randomized 2:1 to RSVpreF 120 μg (n=453) or placebo (n=225) 6
• Demonstrated immunobridging to efficacy versus ≥60-year-olds through noninferiority criteria for RSV-A and RSV-B neutralizing titers 6

mRNA RSV Vaccine (mRNA-1345/mRESVIA) Trials

ConquerRSV Study

• Randomized, placebo-controlled trial contributing safety and efficacy data 1
• Efficacy: 78.7% (95% CI: 62.8-87.9) in first 4 months against RSV-LRTD with ≥2 symptoms 3

Phase I Trial for mRNA Vaccine

• Randomized trial in participants aged 65-79 years 1
• Participants received either the phase II/III trial vaccine formulation or placebo 1

Safety Profile Across Trials

RSVPreF3 Safety

• Serious adverse events similar between vaccine (4.4%) and placebo (4.3%) groups (pooled RR=1.02; 95% CI: 0.91-1.15) 1
• Severe reactogenicity events: 3.8% vaccine vs. 0.9% placebo (pooled RR=4.10; 95% CI: 1.99-8.45) 1
• Inflammatory neurologic events in 3 of 17,922 participants within 42 days: 1 Guillain-Barré syndrome, 2 acute disseminated encephalomyelitis 1

RSVpreF Safety

• Serious adverse events similar between vaccine (4.3%) and placebo (4.1%) groups (pooled RR=1.04; 95% CI: 0.94-1.15) 1
• Severe reactogenicity events: 1.0% vaccine vs. 0.7% placebo (pooled RR=1.43; 95% CI: 0.85-2.39) 1
• Inflammatory neurologic events in 3 of 20,255 participants within 42 days: 1 GBS, 1 Miller Fisher syndrome, 1 undifferentiated motor-sensory axonal polyneuropathy 1

mRNA Vaccine Safety

• Severe reactogenicity events more common with mRNA vaccine (pooled RR=1.54; 95% CI: 1.40-1.68) 1
• Serious adverse events similar between groups (pooled RR=1.00; 95% CI: 0.95-1.05) 1
• No cases of GBS, other inflammatory neurologic events, myocarditis, or pericarditis within 42 days 1

Post-Marketing Surveillance

• CDC reviewed V-safe (N=16,220) and VAERS (N=3,200) data from May 2023 to April 2024 1
• GBS reports: 1.8 per million doses for RSVPreF3 and 4.4 per million doses for RSVpreF, both exceeding expected background rates 1