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JAMA. 2018 Jun 12;319(22):2299-2307. doi: 10.1001/jama.2018.6129.

Effect of Recombinant Human Pentraxin 2 vs Placebo on Change in Forced Vital Capacity in Patients With Idiopathic Pulmonary Fibrosis: A Randomized Clinical Trial.

Author information

1
University of Washington, Seattle.
2
Promedior Inc, Lexington, Massachusetts.
3
University of Kansas, Kansas City.
4
Inova Fairfax Hospital, Falls Church, Virginia.
5
University of California, San Francisco.
6
Department of Respiratory Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
7
First Medical Faculty Charles University and Thomayer Hospital, Prague, Czech Republic.
8
University of Milano-Bicocca, Monza, Italy.
9
Yale School of Medicine, New Haven, Connecticut.
10
University of Wisconsin, Madison.
11
Center for Rare and Interstitial Lung Diseases, Thoraxklinik, University of Heidelberg, Heidelberg, Germany.
12
Venn Life Sciences, Paris, France.
13
Mayo Clinic, Rochester, Minnesota.
14
Unità Operativa Complessa di Pneumologia, IRCCS Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy.

Abstract

Importance:

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Approved therapies do not halt disease progression.

Objective:

To determine the effect of recombinant human pentraxin 2 vs placebo on change from baseline to week 28 in mean forced vital capacity (FVC) percentage of predicted value.

Design, Setting, and Participants:

Phase 2, randomized, double-blind, placebo-controlled trial conducted at 18 sites in 7 countries of eligible patients with IPF (N = 117; aged 40-80 years; FVC ≥50% and ≤90% predicted; ratio of forced expiratory volume in the first second/FVC >0.70; diffusing capacity for carbon monoxide [Dlco] ≥25% and ≤90% predicted; and distance of ≥150 m on the 6-minute walk test). Study period was August 2015-May 2017.

Interventions:

Patients were randomized to receive either recombinant human pentraxin 2 (10 mg/kg intravenous every 4 weeks, n = 77) or placebo (n = 39) for 24 weeks, and stratified by concurrent IPF treatment status.

Main Outcomes and Measures:

The primary end point was the least-squares mean change in FVC percentage of predicted value from baseline to week 28 (minimal clinically important difference, decline of 2%-6%). Secondary end points included mean change in lung volumes (total, normal, and interstitial lung abnormalities) on high-resolution computed tomography (HRCT) and 6-minute walk distance (minimal clinically important difference, 24-45 m).

Results:

Of 117 randomized patients, 116 received at least 1 dose of study drug (mean age, 68.6 years; 81.0% men; mean time since IPF diagnosis, 3.8 years), and 111 (95.7%) completed the study. The least-squares mean change in FVC percentage of predicted value from baseline to week 28 in patients treated with recombinant human pentraxin 2 was -2.5 vs -4.8 for those in the placebo group (difference, +2.3 [90% CI, 1.1 to 3.5]; P = .001). No significant treatment differences were observed in total lung volume (difference, 93.5 mL [90% CI, -27.7 to 214.7]), quantitative parenchymal features on HRCT (normal lung volume difference, -1.2% [90% CI, -4.4 to 1.9]; interstitial lung abnormalities difference, 1.1% [90% CI, -2.2 to 4.3]), or measurement of Dlco (difference, -0.4 [90% CI, -2.6 to 1.7]). The change in 6-minute walk distance was -0.5 m for patients treated with recombinant human pentraxin 2 vs -31.8 m for those in the placebo group (difference, +31.3 m [90% CI, 17.4 to 45.1]; P < .001). The most common adverse events in the recombinant human pentraxin 2 vs placebo group were cough (18% vs 5%), fatigue (17% vs 10%), and nasopharyngitis (16% vs 23%).

Conclusions and Relevance:

In this preliminary study, recombinant human pentraxin 2 vs placebo resulted in a slower decline in lung function over 28 weeks for patients with idiopathic pulmonary fibrosis. Further research should more fully assess efficacy and safety.

Trial Registration:

clinicaltrials.gov Identifier: NCT02550873.

PMID:
29800034
PMCID:
PMC6134440
DOI:
10.1001/jama.2018.6129
[Indexed for MEDLINE]
Free PMC Article

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