Zinpentraxin alfa comparable to placebo in idiopathic pulmonary fibrosis

Key takeaways:

• Patients with idiopathic pulmonary fibrosis taking zinpentraxin alfa had similar reductions in lung function to placebo over 52 weeks.
• Safety results of zinpentraxin alfa were comparable to placebo.

Among patients with idiopathic pulmonary fibrosis, lung function decline was comparable between 52-week zinpentraxin alfa treatment and placebo, according to results published in American Journal of Respiratory and Critical Care Medicine.

“Although well tolerated, no clinical benefit of zinpentraxin alfa over placebo was observed in the STARSCAPE trial in patients with IPF,” Luca Richeldi, MD, PhD, head of the division of respiratory disease at Agostino Gemelli University Hospital and professor of respiratory medicine at Catholic University of the Sacred Heart in Rome, and colleagues wrote.

In a 52-week, double-blind, placebo-controlled, multicenter, pivotal phase 3 trial (STARSCAPE), Richeldi and colleagues assessed 660 adults (mean age, 70.7 years; 80.5% men) with IPF to evaluate the impact of 10 mg/kg of zinpentraxin alfa every 4 weeks for 52 weeks on FVC vs. placebo.

Researchers also compared percent-predicted FVC, 6-minute walking distance and adverse events at week 52 between the two groups.

According to researchers, patients with IPF receiving this treatment for 28 weeks previously demonstrated clinical benefit in a phase 2 trial.

In the phase 3 study population, 330 patients (mean age, 70.8 years; 81.8% men) received zinpentraxin alfa, and the remaining 330 patients (mean age, 70.5%; 79.1% men) received placebo.

The drug had no treatment benefit vs. placebo in a pre-specified futility analysis, leading to early termination of the trial and only 106 patients completing the study (mean treatment exposure, 26.7 weeks), researchers wrote.

When comparing absolute change in FVC from baseline to week 52, the two groups did not significantly differ from each other (zinpentraxin alfa, –235.72 mL; placebo, –214.89 mL).

Researchers further observed comparable absolute changes in percent-predicted FVC and 6-minute walking distance at week 52 in the zinpentraxin alfa group (–6.22 percent predicted FVC; –33.64 m) and the placebo group (–5.75 percent predicted FVC; –24.19 m).

In terms of safety, the proportion of patients reporting at least one adverse event was similar between groups (zinpentraxin alfa, 74.6% vs. placebo, 72.3%). COVID-19 occurred the most frequently in both groups (zinpentraxin alfa, 18.1% vs. placebo, 17.6%), followed by cough (13% vs. 11.6%), diarrhea (10.6% vs. 10.3%) and an infusion-related reaction (9.7% vs. 8.8%).

Of the patients who experienced an adverse event, 15 discontinued treatment, including nine patients receiving zinpentraxin alfa and six patients receiving placebo.

The proportion of patients reporting a serious adverse event in the zinpentraxin alfa group was comparable to the placebo group (13.9% vs. 12.2%). Death was reported for five patients in the treatment group and four patients in the placebo group, according to researchers.

Lastly, researchers reevaluated phase 2 trial data in a post-hoc analysis and found that the clinical benefit of zinpentraxin alfa observed in the study was due to extreme reductions in FVC in two patients from the placebo group.

“The main learnings from this program are that it is important to examine and visualize the data at the patient level, look for outliers that may impact the estimated treatment effect and establish appropriate methods of analyses where such data may be present,” Richeldi and colleagues wrote. “These learnings should be carefully considered and applied to the design of new trials in patients with IPF to maximize their value.”