title: Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: safety, pharmacokinetics and exploratory efficacy.
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.
authors: Dept of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands B.vandenBlink@erasmusmc.nl.
authors: Bernt
authors: B
authors: van den Blink
authors: Centre for Human Drug Research, Leiden, The Netherlands.
authors: Marlous R
authors: MR
authors: Dillingh
authors: Massachusetts General Hospital, Boston, MA, USA.
authors: Leo C
authors: LC
authors: Ginns
authors: Dept of Medicine, Duke University, Durham, NC, USA.
authors: Lake D
authors: LD
authors: Morrison
authors: Centre for Human Drug Research, Leiden, The Netherlands.
authors: Matthijs
authors: M
authors: Moerland
authors: Dept of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors: Marlies
authors: M
authors: Wijsenbeek
authors: Promedior, Inc., Lexington, MA, USA.
authors: Elizabeth G
authors: EG
authors: Trehu
authors: Division of Thoracic Radiology, Mayo Clinic, Rochester, MI, USA.
authors: Brian J
authors: BJ
authors: Bartholmai
authors: Centre for Human Drug Research, Leiden, The Netherlands.
authors: Jacobus
authors: J
authors: Burggraaf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D018398:Homeodomain Proteins / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy*; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics; D012129:Respiratory Function Tests; D000683:Serum Amyloid P-Component / Q000009:adverse effects / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014481:United States
chemical_list: D018398:Homeodomain Proteins; C552898:PRM-151; D011994:Recombinant Proteins; D000683:Serum Amyloid P-Component