scholarly journals SAR156597 in idiopathic pulmonary fibrosis: a phase 2 placebo-controlled study (DRI11772)

2018 ◽  
Vol 52 (6) ◽  
pp. 1801130 ◽  
Author(s):  
Ganesh Raghu ◽  
Luca Richeldi ◽  
Bruno Crestani ◽  
Peter Wung ◽  
Raphael Bejuit ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Vital Capacity ◽  
Interleukin 4 ◽  
Controlled Study ◽  
Serious Adverse Events ◽  
Double Blind ◽  
The Mean ◽  
Dose Levels ◽  
Igg4 Antibody

A phase 2b trial (NCT02345070) was conducted to evaluate the efficacy and safety of two dose levels/regimens of SAR156597 (a bispecific IgG4 antibody that binds and neutralises both circulating interleukin-4 and interleukin-13), in comparison with placebo, administered to patients with idiopathic pulmonary fibrosis (IPF) over 52 weeks.DRI11772 was a multinational randomised double-blind placebo-controlled phase 2b trial. Patients aged >40 years with a documented diagnosis of IPF received SAR156597 200 mg once every week (QW), SAR156597 200 mg once every 2 weeks (Q2W) or placebo, over 52 weeks. The primary efficacy end-point was absolute change from baseline in forced vital capacity (FVC) % predicted at 52 weeks.Of 327 randomised patients, 325 received treatment with placebo (n=109), SAR156597 Q2W (n=108) or SAR156597 QW (n=108). The mean change from baseline in FVC % pred at 52 weeks was –5.8%, –5.2% and –6.3% for the placebo, Q2W and QW arms, respectively (Q2W versus placebo, p=0.59; QW versus placebo, p=0.63). The safety profile observed in the three treatment arms was generally similar, although serious adverse events were more common in the QW arm than in the other arms.The DRI11772 study failed to demonstrate benefit of SAR156597 in the treatment of IPF.

scholarly journals Recombinant human pentraxin-2 therapy in patients with idiopathic pulmonary fibrosis: safety, pharmacokinetics and exploratory efficacy

2016 ◽  
Vol 47 (3) ◽  
pp. 889-897 ◽  
Author(s):  
Bernt van den Blink ◽  
Marlous R. Dillingh ◽  
Leo C. Ginns ◽  
Lake D. Morrison ◽  
Matthijs Moerland ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Study Drug ◽  
Pharmacokinetic Profile ◽  
High Resolution Computed Tomography ◽  
Double Blind ◽  
Dose Trial ◽  
Dose Levels ◽  
Amyloid P ◽  
Dose Dependent

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−1versus 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.

scholarly journals Importance of serial changes in biomarkers in idiopathic pulmonary fibrosis

2017 ◽  
Vol 3 (3) ◽  
pp. 00019-2016 ◽  
Author(s):  
Akihiko Sokai ◽  
Kiminobu Tanizawa ◽  
Tomohiro Handa ◽  
Kumiko Kanatani ◽  
Takeshi Kubo ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Vital Capacity ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Prognostic Information ◽  
The Mean ◽  
Serial Measurements ◽  
Overall Mortality

The clinical significance of serial changes in serum biomarkers in patients with idiopathic pulmonary fibrosis (IPF) remains to be established. This retrospective study was conducted to clarify the associations of serial changes in serum Krebs von den Lungen-6 (KL-6) and surfactant protein-D (SP-D) with changes in physiological indices and overall mortality in IPF.The study subjects were 75 patients with IPF. The 6 month change in serum KL-6 was significantly correlated with changes in the percentage of the predicted forced vital capacity (FVC % pred) and the percentage of the predicted diffusing capacity of the lung for carbon monoxide (% DLCO), while the 6 month change in serum SP-D was correlated only with % DLCO. During the mean follow-up period of 647 days, 22 (29.3%) patients died. An increase in serum KL-6 over a 6 month period was a significant predictor of mortality even after adjustment for %FVC, % DLCO and serum KL-6 at the baseline (hazard ratio 1.10 per 100 U·mL−1, 95% CI 1.01–1.18, p=0.03), whereas the 6 month increase in serum SP-D was not significant.Serial measurements of serum KL-6 may provide additional prognostic information compared to that provided by physiological parameters in patients with IPF.

scholarly journals A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis

2019 ◽  
Vol 53 (3) ◽  
pp. 1801992 ◽  
Author(s):  
Pauline T. Lukey ◽  
Stephen A. Harrison ◽  
Shuying Yang ◽  
Yim Man ◽  
Beverley F. Holman ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Mammalian Target Of Rapamycin ◽  
Common Adverse Event ◽  
Controlled Study ◽  
Pharmacokinetic Analysis ◽  
Experimental Medicine ◽  
Repeat Dose ◽  
Target Engagement ◽  
Double Blind

Phosphatidylinositol 3-kinases (PI3Ks) and mammalian target of rapamycin (mTOR) play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Omipalisib (GSK2126458) is a potent inhibitor of PI3K/mTOR.A randomised, placebo-controlled, double-blind, repeat dose escalation, experimental medicine study of omipalisib in subjects with IPF was conducted (NCT01725139) to test safety, tolerability, pharmacokinetics and pharmacodynamics. Omipalisib was dosed at 0.25 mg, 1 mg and 2 mg twice daily for 8 days in four cohorts of four subjects randomised 3:1 to receive omipalisib or placebo (two cohorts received 2 mg twice daily).17 subjects with IPF were enrolled. The most common adverse event was diarrhoea, which was reported by four participants. Dose-related increases in insulin and glucose were observed. Pharmacokinetic analysis demonstrated that exposure in the blood predicts lung exposure. Exposure-dependent inhibition of phosphatidylinositol 3,4,5 trisphosphate and pAKT confirmed target engagement in blood and lungs. 18F-2-fluoro-2-deoxy-d-glucose(FDG)-positron emission tomography/computed tomography scans revealed an exposure-dependent reduction in 18F-FDG uptake in fibrotic areas of the lung, as measured by target-to-background, ratio thus confirming pharmacodynamic activity.This experimental medicine study demonstrates acceptable tolerability of omipalisib in subjects with IPF at exposures for which target engagement was confirmed both systemically and in the lungs.

scholarly journals Effect of antifibrotic agents on survival in idiopathic pulmonary fibrosis patients according to forced vital capacity: a real-world retrospective cohort study in Japan

2020 ◽  
Author(s):  
Sho Saeki ◽  
Osamu Nishiyama ◽  
Ryo Yamazaki ◽  
Kazuya Yoshikawa ◽  
Ken Shirahase ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Forced Vital Capacity ◽  
Retrospective Cohort ◽  
Vital Capacity ◽  
Survival Prognosis ◽  
Antifibrotic Therapy ◽  
Severe Group ◽  
The Mean ◽  
Antifibrotic Agents

Abstract Background Antifibrotic agents suppress the decline in forced vital capacity (FVC) and disease progression in idiopathic pulmonary fibrosis (IPF) patients. However, their effect on survival prognosis and differences in this effect according to baseline lung function have been unexplored. Therefore, this study aimed to examine the effect of antifibrotics on survival prognosis and whether this effect differed according to baseline FVC. Methods Consecutive IPF patients from January 2008 to May 2019 were examined retrospectively. FVC and effect of pirfenidone or nintedanib therapy were assessed. FVC at registration was used to categorize the patients into mild: FVC % predicted ≥ 80%, moderate: FVC % predicted 50–80%, and severe: FVC % predicted < 50% IPF groups. Results In total, 172 IPF patients were included. The mean FVC % predicted was 77.4 ± 22.2%. The median survival periods of patients in the mild, moderate, and severe IPF groups were 1,452, 1,305, and 481 days, respectively. Significant differences were observed in survival between the mild and severe groups and the moderate and severe groups (p < 0.0001), but not between the mild and moderate groups (p = 0.20). The survival was longer in patients on antifibrotic therapy in the mild (p = 0.18) and moderate groups (p = 0.04), but not in the severe group (p = 0.93). Conclusions Antifibrotics extended the survival of IPF patients. The effect was obvious in patients with FVC % predicted of 50–80%, a tendency was observed in patients with FVC % predicted ≥ 80%, while no effect was observed in patients with FVC % predicted < 50%.

scholarly journals Effectiveness of pirfenidone in idiopathic pulmonary fibrosis according to the autoantibody status: a retrospective cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Myung Jin Song ◽  
Sang Hoon Lee ◽  
Ji Ye Jung ◽  
Young Ae Kang ◽  
Moo Suk Park ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Vital Capacity ◽  
Tertiary Care ◽  
Care Hospital ◽  
Diffusion Capacity ◽  
Autoantibody Status ◽  
The Mean ◽  
One Year ◽  
Positive Groups

Abstract Background Pirfenidone is an anti-fibrotic agent shown to slow the progression of idiopathic pulmonary fibrosis (IPF). However, its effectiveness in association with serological autoimmune features in IPF remains unclear. Methods We retrospectively reviewed the medical records of patients with IPF treated at a tertiary care hospital in South Korea. The autoantibody status was defined as positive if we detected autoantibodies meeting the serological domain criteria for interstitial pneumonia with autoimmune features or anti-neutrophil cytoplasmic antibodies. Results We included 142 patients with IPF treated with pirfenidone for over six months (93 were autoantibody-positive and 49 were autoantibody-negative). The mean age was 69.5 ± 7.3 years, and 77.5% of the patients were male. The adjusted mean changes over one year were − 34.4 and − 112.2 mL (p = 0.168) in forced vital capacity (FVC), and − 0.53 and − 0.72 mL/mmHg/min (p = 0.356) in the lungs diffusion capacity for carbon monoxide (DLCO) in the autoantibody-negative and autoantibody-positive groups, respectively. Conclusions Reductions in FVC and DLCO were similar in autoantibody-positive and autoantibody-negative patients with IPF treated with pirfenidone. Pirfenidone is effective in attenuating the progression of IPF, irrespective of the autoantibody status.

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