Phase 2a Randomized Placebo-Controlled Human Challenge Trial of the RSV L-Protein Inhibitor S-337395 for Respiratory Syncytial Virus Infection.

Summary

In a randomized, double-blind human challenge study, oral S-337395 reduced RSV viral load and symptoms with a clear dose-response, particularly at 30 mg and 300 mg, and was well tolerated. These findings support RSV L-protein inhibition as a promising antiviral strategy.

Key Findings

• S-337395 30 mg and 300 mg reduced qRT-PCR viral load AUC by 64.87% and 88.94%, respectively (both p<0.05).
• Viral culture AUC decreased by 72.32% (30 mg) and 86.17% (300 mg) versus placebo (both p<0.05).
• Total symptom score AUC was 78.15% lower with 300 mg (p<0.05); safety profile showed no concerns.

Clinical Implications

Provides clinical rationale to advance S-337395 to larger patient trials and informs dose selection; supports development of oral RSV antivirals to complement or substitute monoclonal/prefusion F strategies.

Limitations

• Single-center human challenge in healthy adults limits generalizability to high-risk patient populations.
• Short follow-up and surrogate endpoints; clinical outcomes in natural infection not assessed.

Future Directions

Proceed to multi-center patient trials (infants, older adults, comorbidities), evaluate time-to-recovery and hospitalization endpoints, and explore resistance and combination strategies.