PMID- 31122893
OWN - NLM
STAT- MEDLINE
DCOM- 20200702
LR  - 20200702
IS  - 2213-2619 (Electronic)
IS  - 2213-2600 (Linking)
VI  - 7
IP  - 8
DP  - 2019 Aug
TI  - Long-term treatment with recombinant human pentraxin 2 protein in patients with 
      idiopathic pulmonary fibrosis: an open-label extension study.
PG  - 657-664
LID - S2213-2600(19)30172-9 [pii]
LID - 10.1016/S2213-2600(19)30172-9 [doi]
AB  - BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) treated with 
      PRM-151, a recombinant human pentraxin 2 protein, in a phase 2 double-blind, 
      randomised controlled trial had significantly reduced decline in percentage of 
      predicted forced vital capacity (FVC) and stabilised 6-min walking distance 
      compared with placebo over a 28-week period. Here we report the 76-week results 
      of an open-label extension study. METHODS: Patients who completed the 28-week 
      double-blind period of the PRM-151-202 trial were eligible to participate in the 
      open-label extension study. Patients previously enrolled in the PRM-151 group 
      continued this treatment and those previously in the placebo group crossed over 
      to PRM-151. All patients received PRM-151 in 28-week cycles with loading doses of 
      10 mg/kg by 60 min intravenous infusions on days 1, 3, and 5 in the first week of 
      each cycle followed by one infusion of 10 mg/kg every 4 weeks. The primary 
      objective of the open-label extension study was to assess the long-term safety 
      and tolerability of PRM-151, which were assessed by analysing adverse events 
      (AEs) up to week 76 in all patients who received at least one dose of PRM-151 
      during the open-label extension study. Exploratory efficacy analyses were done by 
      assessing changes from baseline in percentage of predicted FVC and 6-min walking 
      distance, with descriptive statistics to week 76 and with random-intercept mixed 
      models to week 52. This study is registered with ClinicalTrials.gov, number 
      NCT02550873, and with EudraCT, number 2014-004782-24. FINDINGS: Of 116 patients 
      who completed the double-blind treatment period, 111 entered the open-label 
      extension study (74 from the PRM-151 group and 37 from the placebo group). 84 
      (76%) of 111 patients received concomitant IPF therapy (pirfenidone n=55 or 
      nintedanib n=29). AEs were consistent with long-term IPF sequelae. 31 (28%) 
      patients had serious AEs. Those occurring in two or more patients were pneumonia 
      (six [5%] of 111), IPF exacerbation (four [4%]), IPF progression (four [4%]), and 
      chest pain (two [2%]). 21 (19%) patients had severe AEs, of which IPF 
      exacerbation and IPF progression each occurred in two (2%) patients. Two (2%) 
      patients experienced life-threatening AEs (one had pneumonia and one had 
      small-cell lung cancer extensive stage). A persistent treatment effect was 
      observed for PRM-151 in patients who continued treatment, with a decline in 
      percentage of predicted FVC of -3.6% per year and in 6-min walking distance of 
      -10.5 m per year at week 52. In patients who started PRM-151 during the 
      open-label extension study, compared with the slopes for placebo, decline reduced 
      for percentage of predicted FVC (from -8.7% per year in weeks 0-28 to -0.9% per 
      year in weeks 28-52, p<0.0001) and 6-min walking distance (from -54.9 m per year 
      to -3.5 m per year, p=0.0224). INTERPRETATION: Long-term treatment with PRM-151 
      was well tolerated and the effects on percentage of predicted FVC and 6-min 
      walking distance were persistent on continuation and positive in patients who 
      crossed over from placebo. These findings support further study of PRM-151 in 
      larger populations of patients with IPF. FUNDING: Promedior.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Raghu, Ganesh
AU  - Raghu G
AD  - Center for Interstitial Lung Diseases, Department of Medicine and Laboratory 
      Medicine, University of Washington, Seattle, WA, USA. Electronic address: 
      graghu@uw.edu.
FAU - van den Blink, Bernt
AU  - van den Blink B
AD  - Promedior, Lexington, MA, USA.
FAU - Hamblin, Mark J
AU  - Hamblin MJ
AD  - Pulmonary and Critical Care Medicine, University of Kansas Medical Center, Kansas 
      City, KS, USA.
FAU - Brown, A Whitney
AU  - Brown AW
AD  - Inova Fairfax Hospital, Falls Church, VA, USA.
FAU - Golden, Jeffrey A
AU  - Golden JA
AD  - Department of Medicine, University of California, San Francisco, San Francisco, 
      CA, USA.
FAU - Ho, Lawrence A
AU  - Ho LA
AD  - Center for Interstitial Lung Diseases, Department of Medicine and Laboratory 
      Medicine, University of Washington, Seattle, WA, USA.
FAU - Wijsenbeek, Marlies S
AU  - Wijsenbeek MS
AD  - Department of Respiratory Medicine, Erasmus MC, University Medical Center, 
      Rotterdam, Netherlands.
FAU - Vasakova, Martina
AU  - Vasakova M
AD  - Department of Respiratory Medicine, First Faculty of Medicine of Charles 
      University and Thomayer Hospital, Prague, Czech Republic.
FAU - Pesci, Alberto
AU  - Pesci A
AD  - School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
FAU - Antin-Ozerkis, Danielle E
AU  - Antin-Ozerkis DE
AD  - Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, 
      CT, USA.
FAU - Meyer, Keith C
AU  - Meyer KC
AD  - Department of Medicine, Division of Pulmonary and Critical Care, University of 
      Wisconsin School of Medicine and Public Health, Madison, WI, USA.
FAU - Kreuter, Michael
AU  - Kreuter M
AD  - Center for Interstitial and Rare Lung Diseases, Thoraxklinik, University of 
      Heidelberg and German Center for Lung, Research, Heidelberg, Germany.
FAU - Moran, Donna
AU  - Moran D
AD  - Promedior, Lexington, MA, USA.
FAU - Santin-Janin, Hugues
AU  - Santin-Janin H
AD  - Venn Life Sciences, Paris, France.
FAU - Aubin, Francois
AU  - Aubin F
AD  - Venn Life Sciences, Paris, France.
FAU - Mulder, Geert-Jan
AU  - Mulder GJ
AD  - Promedior, Lexington, MA, USA.
FAU - Gupta, Renu
AU  - Gupta R
AD  - Promedior, Lexington, MA, USA.
FAU - Richeldi, Luca
AU  - Richeldi L
AD  - Fondazione Policlinico Universitario A Gemelli IRCCS, Universita Cattolica del 
      Sacro Cuore, Rome, Italy.
LA  - eng
SI  - ClinicalTrials.gov/NCT02550873
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190520
PL  - England
TA  - Lancet Respir Med
JT  - The Lancet. Respiratory medicine
JID - 101605555
RN  - 0 (Homeodomain Proteins)
RN  - 0 (PRM-151)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Serum Amyloid P-Component)
SB  - IM
CIN - Lancet Respir Med. 2019 Aug;7(8):640-641. PMID: 31122900
MH  - Aged
MH  - Cross-Over Studies
MH  - Double-Blind Method
MH  - Female
MH  - Homeodomain Proteins/*therapeutic use
MH  - Humans
MH  - Idiopathic Pulmonary Fibrosis/*drug therapy
MH  - Long-Term Care
MH  - Male
MH  - Recombinant Proteins/therapeutic use
MH  - Serum Amyloid P-Component/*therapeutic use
MH  - Treatment Outcome
MH  - Vital Capacity
EDAT- 2019/05/28 06:00
MHDA- 2020/07/03 06:00
CRDT- 2019/05/25 06:00
PHST- 2019/02/28 00:00 [received]
PHST- 2019/04/12 00:00 [revised]
PHST- 2019/04/13 00:00 [accepted]
PHST- 2019/05/28 06:00 [pubmed]
PHST- 2020/07/03 06:00 [medline]
PHST- 2019/05/25 06:00 [entrez]
AID - S2213-2600(19)30172-9 [pii]
AID - 10.1016/S2213-2600(19)30172-9 [doi]
PST - ppublish
SO  - Lancet Respir Med. 2019 Aug;7(8):657-664. doi: 10.1016/S2213-2600(19)30172-9. 
      Epub 2019 May 20.