Abnormal fibrogenic repair response upon alveolar injury is believed to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). PRM-151 (recombinant human pentraxin-2, also known as serum amyloid P), has been shown to reduce fibrosis in preclinical lung fibrosis models, and was well tolerated with a favourable pharmacokinetic profile in an earlier single-dose phase I study.
A randomised, double-blind, placebo-controlled, multiple ascending dose trial was performed to assess the tolerability and pharmacokinetic and pharmacodynamic characteristics of multiple doses of PRM-151 in IPF patients. Subjects in three successive cohorts (1, 5, or 10 mg·kg−1 versus placebo) received intravenous study drug on days 1, 3, 5, 8 and 15, and were followed-up to day 57.
PRM-151 was well tolerated at all dose levels, with no serious adverse reactions. Administration of PRM-151 resulted in two- to eight-fold dose-dependent increases in circulating pentraxin-2 levels. Forced vital capacity and 6-min walk test showed trends towards improvement in the combined PRM-151 dose groups. On high-resolution computed tomography scans, stable or improved lung volume unoccupied by interstitial lung abnormality was noted in some PRM-151 subjects compared to placebo subjects on day 57.
The efficacy of PRM-151 in IPF remains to be investigated in dedicated future trials.
Recombinant human pentraxin-2 increased serum levels safely in IPF patients and may improve lung function http://ow.ly/WaqDQ
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Support statement: This study was funded by Promedior, Inc. All authors received clinical trial support from Promedior, Inc. E.G. Trehu is an employee of Promedior, Inc. Funding information for this article has been deposited with FundRef.
Conflict of interest: Disclosures can be found alongside the online version of this article at erj.ersjournals.com
- Received May 29, 2015.
- Accepted December 7, 2015.
- Copyright ©ERS 2016