TY - JOUR
T1 - Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis
T2 - Safety, pharmacokinetics and exploratory efficacy
AU - Van Den Blink, Bernt
AU - Dillingh, Marlous R.
AU - Ginns, Leo C.
AU - Morrison, Lake D.
AU - Moerland, Matthijs
AU - Wijsenbeek, Marlies
AU - Trehu, Elizabeth G.
AU - Bartholmai, Brian J.
AU - Burggraaf, Jacobus
N1 - Publisher Copyright:
© ERS 2016.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
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U2 - 10.1183/13993003.00850-2015
DO - 10.1183/13993003.00850-2015
M3 - Article
C2 - 26869678
AN - SCOPUS:84959906529
SN - 0903-1936
VL - 47
SP - 889
EP - 897
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 3
ER -