Effects of the DPP-1 inhibitor HSK31858 in adults with bronchiectasis in China (SAVE-BE): a phase 2, multicentre, double-blind, randomised, placebo-controlled trial.
Summary
In a multicenter phase 2 RCT (n=224), HSK31858 (20 mg or 40 mg daily for 24 weeks) significantly reduced annualized exacerbation frequency versus placebo (IRR 0.52 and 0.41, respectively) in adults with bronchiectasis. Safety profiles were similar across groups without increases in adverse events of special interest.
Key Findings
- Annualized exacerbation frequency reduced versus placebo (IRR 0.52 at 20 mg; IRR 0.41 at 40 mg; both statistically significant).
- Consistent safety with no increase in adverse events of special interest (e.g., hyperkeratosis, gingivitis, life-threatening infections).
- Effect observed over 24 weeks across a multicenter Chinese cohort with stratification by prior exacerbation frequency.
Clinical Implications
If confirmed in phase 3, HSK31858 or similar DPP-1 inhibitors could be added to standard care to reduce exacerbations in bronchiectasis, especially in frequent exacerbators, without apparent new safety concerns.
Why It Matters
This trial provides the first robust randomized evidence that DPP-1 inhibition can reduce exacerbations in bronchiectasis, a condition with few disease-modifying therapies. It validates neutrophil protease activation as a tractable therapeutic axis.
Limitations
- Phase 2 duration (24 weeks) limits long-term efficacy and safety assessment.
- Single-country (China) study may limit generalizability to other populations and etiologies of bronchiectasis.
Future Directions
Conduct phase 3 multinational trials with longer follow-up, explore biomarkers of neutrophil activity to enrich responders, and assess effects on quality of life, lung function, and microbiology.
Study Information
- Study Type
- RCT
- Research Domain
- Treatment
- Evidence Level
- II - Well-designed randomized, double-blind, placebo-controlled phase 2 trial.
- Study Design
- OTHER