Abstract
Background: Recombinant human pentraxin-2 (rhPTX-2) significantly decreased decline in percent predicted forced vital capacity (FVC) and stabilized 6-min walk distance (6MWD) in patients with idiopathic pulmonary fibrosis (IPF) during the 28-week, placebo-controlled, randomized period of the Phase II PRM-151–202 study. Interim (76-week) data from the open-label extension (OLE) demonstrated sustained safety and efficacy with rhPTX-2 treatment. Here, we present the entire long-term OLE safety and efficacy data to 128 weeks. Methods: Patients who completed the randomized PRM-151–202 study period were eligible for the OLE, during which all patients received rhPTX-2, having started rhPTX-2 (i.e., crossed from placebo) or continued rhPTX-2 after Week 28. rhPTX-2 was administered in 28-week cycles, with 10 mg/kg intravenous infusions (60 min) on Days 1, 3, and 5 in the first week of each cycle, then one infusion every 4 weeks up to Week 128. The OLE primary objective was to assess the long-term safety and tolerability of rhPTX-2. Other outcomes included FVC, 6MWD, and patient-reported outcomes (descriptive analysis). Results: All 111 patients who completed the randomized period entered the OLE (n = 37 started rhPTX-2; n = 74 continued rhPTX-2); 57 (51.4%) completed to Week 128. The treatment-emergent adverse event (TEAE) profile was consistent with the randomized period, with the majority of TEAEs graded mild or moderate. Serious TEAEs occurred in 47 patients (42.3%), most frequently IPF (n = 11; 9.9%), pneumonia (n = 7; 6.3%), and acute respiratory failure (n = 3; 2.7%). Three patients underwent lung transplantation. Most serious TEAEs (and all 14 fatal events) were considered unrelated to rhPTX-2 treatment. For patients starting vs continuing rhPTX-2, mean (95% confidence interval) changes from baseline to Week 128 were, respectively, − 6.2% (− 7.7; − 4.6) and − 5.7% (− 8.0; − 3.3) for percent predicted FVC and − 36.3 m (− 65.8; − 6.9) and − 28.9 m (− 54.3; − 3.6) for 6MWD; however, conclusions were limited by patient numbers at Week 128. Conclusions: Long-term treatment (up to 128 weeks) with rhPTX-2 was well tolerated in patients with IPF, with no new safety signals emerging in the OLE. The limited efficacy data over 128 weeks may suggest a trend towards a treatment effect. Trial registration NCT02550873; EudraCT 2014-004782-24.
| Original language | English |
|---|---|
| Article number | 129 |
| Journal | Respiratory Research |
| Volume | 23 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 21 May 2022 |
Bibliographical note
Funding Information:JAG has received a research support grant from Promedior (now a fully owned subsidiary of F. Hoffmann-La Roche, Ltd.).
Funding Information:
MJH has received research grant support from Promedior (now a fully owned subsidiary of F. Hoffmann-La Roche, Ltd.) during the conduct of the study; and outside the submitted work: a clinical trial research grant and a medical education grant from Boehringer Ingelheim, and clinical trial research grants from Roche-Genentech, Biogen, Fibrogen, and Global Blood Therapeutics; and personal fees from Boehringer Ingelheim and Roche-Genentech for serving as a contracted speaker.
Funding Information:
We thank the patients for their time and participation in the trial and the study coordinators at each site. We also thank Renu Gupta and Bernt Van Den Blink, previously employed by Promedior, Inc. (now a fully owned subsidiary of F. Hoffmann-La Roche, Ltd.) for supporting this study, and Francois Aubin from Venn Life Sciences, Paris, France, for preparing and performing the data analyses. Medical writing support was provided by Rebecca Newbould and Zaavan Baildon of CMC AFFINITY, McCann Health Medical Communications, funded by F. Hoffmann-La Roche, Ltd.
Funding Information:
We thank the patients for their time and participation in the trial and the study coordinators at each site. We also thank Renu Gupta and Bernt Van Den Blink, previously employed by Promedior, Inc. (now a fully owned subsidiary of F. Hoffmann-La Roche, Ltd.) for supporting this study, and Francois Aubin from Venn Life Sciences, Paris, France, for preparing and performing the data analyses. Medical writing support was provided by Rebecca Newbould and Zaavan Baildon of CMC AFFINITY, McCann Health Medical Communications, funded by F. Hoffmann-La Roche, Ltd.
Publisher Copyright:
© 2022, The Author(s).