Imperial College London
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ProfessorPhilipMolyneaux

Faculty of Medicine, National Heart & Lung Institute

Professor of Interstitial Lung Disease
 
 
 
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p.molyneaux

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Maher:2020:10.1186/s12931-020-01339-7,
author = {Maher, TM and Simpson, JK and Porter, JC and Wilson, FJ and Chan, R and Eames, R and Cui, Y and Siederer, S and Parry, S and Kenny, J and Slack, RJ and Sahota, J and Paul, L and Saunders, P and Molyneaux, PL and Lukey, PT and Rizzo, G and Searle, GE and Marshall, RP and Saleem, A and Kang'ombe, AR and Fairman, D and Fahy, WA and Vahdati-Bolouri, M},
doi = {10.1186/s12931-020-01339-7},
journal = {Respiratory Research},
title = {A positron emission tomography imaging study to confirm target engagement in the lungs of patients with idiopathic pulmonary fibrosis following a single dose of a novel inhaled αvβ6 integrin inhibitor},
url = {http://dx.doi.org/10.1186/s12931-020-01339-7},
volume = {21},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with poor prognosis and a significant unmet medical need. This study evaluated the safety, pharmacokinetics (PK) and target engagement in the lungs, of GSK3008348, a novel inhaled alpha-v beta-6 (αvβ6) integrin inhibitor, in participants with IPF.MethodsThis was a phase 1b, randomised, double-blind (sponsor unblind) study, conducted in the UK (two clinical sites, one imaging unit) between June 2017 and July 2018 (NCT03069989). Participants with a definite or probable diagnosis of IPF received a single nebulised dose of 1000 mcg GSK3008348 or placebo (ratio 5:2) in two dosing periods. In period 1, safety and PK assessments were performed up to 24 h post-dose; in period 2, after a 7-day to 28-day washout, participants underwent a total of three positron emission tomography (PET) scans: baseline, Day 1 (~ 30 min post-dosing) and Day 2 (~ 24 h post-dosing), using a radiolabelled αvβ6-specific ligand, [18F]FB-A20FMDV2. The primary endpoint was whole lung volume of distribution (VT), not corrected for air volume, at ~ 30 min post-dose compared with pre-dose. The study success criterion, determined using Bayesian analysis, was a posterior probability (true % reduction in VT > 0%) of ≥80%.ResultsEight participants with IPF were enrolled and seven completed the study. Adjusted posterior median reduction in uncorrected VT at ~ 30 min after GSK3008348 inhalation was 20% (95% CrI: − 9 to 42%). The posterior probability that the true % reduction in VT > 0% was 93%. GSK3008348 was well tolerated with no reports of serious adverse events or clinically significant abnormalities that were attributable to study treatment. PK was successfully characterised showing rapid absorption followed by a multiphasic elimination.ConclusionsThis study demonstrated engagement of th
AU  - Maher,TM
AU  - Simpson,JK
AU  - Porter,JC
AU  - Wilson,FJ
AU  - Chan,R
AU  - Eames,R
AU  - Cui,Y
AU  - Siederer,S
AU  - Parry,S
AU  - Kenny,J
AU  - Slack,RJ
AU  - Sahota,J
AU  - Paul,L
AU  - Saunders,P
AU  - Molyneaux,PL
AU  - Lukey,PT
AU  - Rizzo,G
AU  - Searle,GE
AU  - Marshall,RP
AU  - Saleem,A
AU  - Kang'ombe,AR
AU  - Fairman,D
AU  - Fahy,WA
AU  - Vahdati-Bolouri,M
DO  - 10.1186/s12931-020-01339-7
PY  - 2020///
SN  - 1465-9921
TI  - A positron emission tomography imaging study to confirm target engagement in the lungs of patients with idiopathic pulmonary fibrosis following a single dose of a novel inhaled αvβ6 integrin inhibitor
T2  - Respiratory Research
UR  - http://dx.doi.org/10.1186/s12931-020-01339-7
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000522256100003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/78953
VL  - 21
ER  -
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