Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis

Safety, pharmacokinetics and exploratory efficacy

Bernt Van Den Blink, Marlous R. Dillingh, Leo C. Ginns, Lake D. Morrison, Matthijs Moerland, Marlies Wijsenbeek, Elizabeth G. Trehu, Brian Jack Bartholmai, Jacobus Burggraaf

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)889-897
Number of pages9
JournalEuropean Respiratory Journal
Volume47
Issue number3
DOIs
StatePublished - Mar 1 2016

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Idiopathic Pulmonary Fibrosis
Pharmacokinetics
Safety
Placebos
Lung
Therapeutics
Fibrosis
Vital Capacity
PRM-151
Amyloid
Tomography
Wounds and Injuries
Serum
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Van Den Blink, B., Dillingh, M. R., Ginns, L. C., Morrison, L. D., Moerland, M., Wijsenbeek, M., ... Burggraaf, J. (2016). Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: Safety, pharmacokinetics and exploratory efficacy. European Respiratory Journal, 47(3), 889-897. https://doi.org/10.1183/13993003.00850-2015

Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis : Safety, pharmacokinetics and exploratory efficacy. / Van Den Blink, Bernt; Dillingh, Marlous R.; Ginns, Leo C.; Morrison, Lake D.; Moerland, Matthijs; Wijsenbeek, Marlies; Trehu, Elizabeth G.; Bartholmai, Brian Jack; Burggraaf, Jacobus.

In: European Respiratory Journal, Vol. 47, No. 3, 01.03.2016, p. 889-897.

Research output: Contribution to journalArticle

Van Den Blink, B, Dillingh, MR, Ginns, LC, Morrison, LD, Moerland, M, Wijsenbeek, M, Trehu, EG, Bartholmai, BJ & Burggraaf, J 2016, 'Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: Safety, pharmacokinetics and exploratory efficacy', European Respiratory Journal, vol. 47, no. 3, pp. 889-897. https://doi.org/10.1183/13993003.00850-2015
Van Den Blink, Bernt ; Dillingh, Marlous R. ; Ginns, Leo C. ; Morrison, Lake D. ; Moerland, Matthijs ; Wijsenbeek, Marlies ; Trehu, Elizabeth G. ; Bartholmai, Brian Jack ; Burggraaf, Jacobus. / Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis : Safety, pharmacokinetics and exploratory efficacy. In: European Respiratory Journal. 2016 ; Vol. 47, No. 3. pp. 889-897.
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