Original Investigation
May 19, 2024
Pamrevlumab for Idiopathic Pulmonary Fibrosis: The ZEPHYRUS-1 Randomized Clinical Trial
Ganesh Raghu, Luca Richeldi, Evans R. Fernández Pérez, et al
JAMA. Published online May 19, 2024. doi:10.1001/jama.2024.8693
Question Does the connective tissue growth factor inhibitor pamrevlumab decrease the rate of decline in lung function for patients with idiopathic pulmonary fibrosis compared with placebo?
Findings In this phase 3 randomized clinical trial including 356 adults with idiopathic pulmonary fibrosis, the decline in forced vital capacity at 48 weeks did not differ significantly between patients treated with pamrevlumab (–260 mL) vs placebo (–330 mL).
Meaning Use of pamrevlumab among patients with idiopathic pulmonary fibrosis did not result in a difference in decline in forced vital capacity from baseline to 48 weeks compared with placebo.
Abstract
Importance Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events.
Objective To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis.
Design, Setting, and Participants Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023.
Interventions Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks.
Main Outcomes and Measures The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported.
Results Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, −260 mL [95% CI, −350 to −170 mL] in the pamrevlumab group vs −330 mL [95% CI, −430 to −230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, −60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group).
Conclusions and Relevance Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48.
Trial Registration ClinicalTrials.gov Identifier: NCT03955146
