Phosphodiesterase 4 (PDE4) inhibition is associated with anti-inflammatory and antifibrotic effects that may be beneficial in patients with idiopathic pulmonary fibrosis.
In this phase 2, double-blind, placebo-controlled trial, we investigated the efficacy and safety of BI 1015550, an oral preferential inhibitor of the PDE4B subtype, in patients with idiopathic pulmonary fibrosis. Patients were randomized in a 2:1 ratio to receive BI 1015550 at a dose of 18 mg twice daily or placebo. The primary endpoint was the change from baseline in forced vital capacity (FVC) at 12 weeks, which we analyzed separately with a Bayesian approach as a function of agent use or non-use. antifibrotic.
A total of 147 patients were randomized to receive BI 1015550 or placebo. Among patients without background antifibrotic therapy, the median change in FVC was 5.7 ml (95% credibility interval, –39.1 to 50.5) in the BI 1015550 group and –81.7 ml (95% credibility interval, –133.5 to –44.8) in the BI 1015550 group. placebo group (median difference, 88.4 ml; 95% credibility interval, 29.5 to 154.2; probability that BI 1015550 is superior to placebo, 0.998). Among patients with background antifibrotic use, the median change in FVC was 2.7 ml (95% credibility interval, -32.8 to 38.2) in the BI 1015550 group and -59.2 ml (95% credibility interval, -111.8 to -17.9) in the placebo group (median difference, 62.4 ml; 95% credibility interval, 6.3 to 125.5; probability that BI 1015550 is superior to placebo, 0.986). A mixed model with repeated measures analysis provided results consistent with those of the Bayesian analysis. The most common adverse event was diarrhea. A total of 13 patients discontinued treatment with BI 1015550 due to adverse events. The percentages of patients with serious adverse events or serious adverse events were similar in the two trial groups.
In this placebo-controlled trial, treatment with BI 1015550, alone or with background use of an antifibrotic agent, prevented a decrease in lung function in patients with idiopathic pulmonary fibrosis. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number 1305-0013, NCT04419506.)