Zinpentraxin Alfa for Idiopathic Pulmonary Fibrosis: The Randomized Phase III STARSCAPE Trial.

RATIONALE: A phase II trial reported clinical benefit over 28 weeks in patients with idiopathic pulmonary fibrosis who received zinpentraxin alfa.

OBJECTIVES: To investigate the efficacy and safety of zinpentraxin alfa in patients with idiopathic pulmonary fibrosis in a phase III trial.

METHODS: This 52-week phase III, double-blind, placebo-controlled, pivotal trial was conducted at 275 sites in 29 countries. Patients with idiopathic pulmonary fibrosis were randomized 1:1 to intravenous placebo or zinpentraxin alfa 10 mg/kg every four weeks. The primary endpoint was absolute change from baseline to Week 52 in forced vital capacity. Secondary endpoints included absolute change from baseline to Week 52 in percent predicted forced vital capacity and six-minute walking distance. Safety was monitored via adverse events. Post-hoc analysis of the phase II and phase III data explored changes in forced vital capacity and their impact on the efficacy results.

MEASUREMENTS AND MAIN RESULTS: Of 664 randomized patients, 333 were assigned to placebo and 331 to zinpentraxin alfa. Four of the 664 randomized patients were never administered study drug. The trial was terminated early following a pre-specified futility analysis that demonstrated no treatment benefit of zinpentraxin alfa over placebo. In the final analysis, absolute change from baseline to Week 52 in forced vital capacity was similar between placebo and zinpentraxin alfa (‒214.89 mL and ‒235.72 mL; P = 0.5420); there were no apparent treatment effects on secondary endpoints. Overall, 72.3% and 74.6% of patients receiving placebo and zinpentraxin alfa, respectively, experienced ≥1 adverse event. Post-hoc analysis revealed that extreme forced vital capacity decline in two placebo-treated patients resulted in the clinical benefit of zinpentraxin alfa reported by phase II.

CONCLUSIONS: Zinpentraxin alfa treatment did not benefit patients with idiopathic pulmonary fibrosis over placebo. Learnings from this program may help improve decision-making around trials in idiopathic pulmonary fibrosis. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/). Clinical trial registration available at www.

CLINICALTRIALS: gov, ID: NCT04552899.