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Eur Respir J. 2016 Mar;47(3):889-97. doi: 10.1183/13993003.00850-2015. Epub 2016 Feb 11.

Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: safety, pharmacokinetics and exploratory efficacy.

Author information

1
Dept of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands B.vandenBlink@erasmusmc.nl.
2
Centre for Human Drug Research, Leiden, The Netherlands.
3
Massachusetts General Hospital, Boston, MA, USA.
4
Dept of Medicine, Duke University, Durham, NC, USA.
5
Dept of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
6
Promedior, Inc., Lexington, MA, USA.
7
Division of Thoracic Radiology, Mayo Clinic, Rochester, MI, USA.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01254409.

PMID:
26869678
DOI:
10.1183/13993003.00850-2015
[Indexed for MEDLINE]
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