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 | Bernt van den Blink, Marlous R Dillingh, Leo C Ginns, Lake D Morrison, Matthijs Moerland, Marlies Wijsenbeek, Elizabeth G Trehu, Brian J Bartholmai, Jacobus Burggraaf |
Journal | The European respiratory journal
(Eur Respir J)
Vol. 47
Issue 3
Pg. 889-97
(Mar 2016)
ISSN: 1399-3003 [Electronic] England |
PMID | 26869678
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright ©ERS 2016. |
Chemical References |
- Homeodomain Proteins
- PRM-151
- Recombinant Proteins
- Serum Amyloid P-Component
|
Topics |
- Adult
- Aged
- Aged, 80 and over
- Dose-Response Relationship, Drug
- Double-Blind Method
- Exercise Test
- Female
- Homeodomain Proteins
(adverse effects, pharmacokinetics)
- Humans
- Idiopathic Pulmonary Fibrosis
(drug therapy)
- Lung
(physiopathology)
- Male
- Middle Aged
- Netherlands
- Recombinant Proteins
(adverse effects, pharmacokinetics)
- Respiratory Function Tests
- Serum Amyloid P-Component
(adverse effects, pharmacokinetics)
- Treatment Outcome
- United States
|