STARSCAPE: Zinpentraxin alfa does not ameliorate health status in IPF

Treatment with zinpentraxin alfa did not result in a clinical benefit for patients with idiopathic pulmonary fibrosis (IPF) in the phase 3 STARSCAPE trial. Since the prognosis of patients with IPF is poor and current antifibrotic agents are associated with (severe) side effects,
lessons need to be learned from this trial to maximise the value of future trials.

Zinpentraxin alfa, which is a recombinant form of human pentraxin-2, was associated with clinical improvements in patients with IPF in a phase 2 study [1]. To confirm these findings, Prof. Luca Richeldi (University of Southampton, UK) and co-investigators designed the phase 3 STARSCAPE trial, to further assess the efficacy and safety of this agent in a population of patients with IPF [2,3]. Included participants (n=660) were randomised 1:1 to treatment with zinpentraxin or a placebo. Also, concomitant therapy with standard-of-care antifibrotic therapy was permitted. The primary endpoint was the absolute change from baseline to week 52 in FVC.

“The STARSCAPE trial was terminated early following a pre-specified futility analysis showing no treatment benefit of zinpentraxin over placebo (ΔFVC of -235.7 mL vs -214.9 mL; P=0.54),” said Dr Richeldi. Secondary endpoints did not suggest that patients treated with zinpentraxin could benefit from this agent in terms of health outcomes either. Following these disappointing results, the authors performed a post-hoc analysis of the previously published phase 2 study that had encouraging results for zinpentraxin in the IPF population. “The data of the post-hoc analysis revealed that 2 outliers in the FVC decline outcomes of placebo-treated patients accounted for a large part of the effect that was observed in this smaller study,” explained Dr Richeldi. “The lesson we should take from this is that we need to be cautious when it comes to analysing and interpreting FVC data that contains outliers.”

1. Raghu G, et al. Lancet Respir Med. 2019;7(8):657-664
2. Richeldi L, et al. Am J Respir Crit Care Med. 2024 May 1;209(9):1132-1140.
3. Richeldi L, et al. Zinpentraxin alfa in patients with idiopathic pulmonary fibrosis: results and learnings from the phase III STARSCAPE trial. C95: New clinical trial results in chronic lung disease. ATS 2024, 17–22 May, San Diego, USA.

Medical writing support was provided by Robert van den Heuvel.

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Posted on 11 June 202411 June 2024