FIBRONEER-IPF (nerandomilast low-dose)
Trial question
What is the role of nerandomilast, a preferential PDE4B inhibitor, in patients with idiopathic pulmonary fibrosis?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
17.0% female
83.0% male
N = 785
785 patients (131 female, 654 male).
Inclusion criteria: patients with idiopathic pulmonary fibrosis.
Key exclusion criteria: prebronchodilator FEV1/FVC < 0.7 at visit 1; other clinically significant pulmonary abnormalities; acute idiopathic pulmonary fibrosis exacerbation within 3 months prior to visit 1 and/or during the screening period; relevant chronic or acute infections, including HIV and viral hepatitis; major surgery performed within 6 weeks prior to visit 2 or planned during the trial period.
Interventions
N=392 nerandomilast (at a dose of 9 mg BID).
N=393 placebo (matching placebo BID).
Primary outcome
Mean decline in forced vital capacity at week 52
138.6 mL
183.5 mL
183.5 mL
137.6 mL
91.8 mL
45.9 mL
0.0 mL
Nerandomilast
Placebo
Significant
decrease ▼
Significant decrease in mean decline in FVC at week 52 (138.6 mL vs. 183.5 mL; MD -44.9, 95% CI -83.3 to -6.4).
Secondary outcomes
No significant difference in first acute exacerbation, hospitalization for a respiratory cause, or death (20.2% vs. 20.4%; HR 1.03, 95% CI 0.75 to 1.41).
No significant difference in acute exacerbation or death (13% vs. 12.5%; HR 1.12, 95% CI 0.76 to 1.67).
No significant difference in hospitalization for a respiratory cause or death (17.3% vs. 18.6%; HR 0.98, 95% CI 0.7 to 1.36).
Safety outcomes
No significant difference in adverse and serious adverse events.
Conclusion
In patients with idiopathic pulmonary fibrosis, nerandomilast was superior to placebo with respect to mean decline in FVC at week 52.
Reference
Luca Richeldi, Arata Azuma, Vincent Cottin et al. Nerandomilast in Patients with Idiopathic Pulmonary Fibrosis. N Engl J Med. 2025 May 18. Online ahead of print.
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