A Proof of Mechanism Study With GSK2126458 in Patients With Idiopathic Pulmonary Fibrosis (IPF)

Summary

This is a dose escalation/dose finding, double-blind, placebo-controlled, parallel study of GSK2126458 in subjects with IPF. The study is designed to explore a number of doses of GSK2126458 for engagement of pharmacology after short term dosing. It is anticipated that approximately 24 subjects will be enrolled in this study. Actual number of cohorts in this study could vary up to a maximum of 6 cohorts (n=4/cohort; 3 on active and 1 on placebo). Each cohort will consist of four subjects who will be randomised to receive GSK2126458 (three subjects) or placebo (one subject) for approximately 8 days (7 to 10 days). On Day 1 they will receive their first dose of GSK2126458 (or placebo) and safety, tolerability and PK/PD in the blood will be measured for up to 8 hours post-dose. Subjects will then be discharged from the site with study drug until the last day of dosing. They will also receive hand held spirometers and instructions on action to be taken in case of deterioration in pulmonary function or any other adverse events (AEs). On the last day of dosing they will return to the site for a repeat of the Day 1 procedures. A bronchoalveolar lavage (BAL) and \[18F\]-fluoro-deoxyglucose (FDG)- positron emission tomography / computed tomography (PET/CT) scan will be conducted twice during the study; once, at least 2 days before dosing commences and again during the course of the dosing period. After the final subject in each cohort has completed dosing, a dose escalation meeting will take place. Safety and tolerability and PK data will be reviewed during this meeting and decisions made may include but are not limited to: escalate the dose, decrease the dose or repeat the same dose in the next cohort; stop the study.

Timeline

Start

2013-03-08

Primary completion

2016-07-12

Completion

2016-07-12

Publications

• Background Lukey PT, Harrison SA, Yang S, Man Y, Holman BF, Rashidnasab A, Azzopardi G, Grayer M, Simpson JK, Bareille P, Paul L, Woodcock HV, Toshner R, Saunders P, Molyneaux PL, Thielemans K, Wilson FJ, Mercer PF, Chambers RC, Groves AM, Fahy WA, Marshall RP, Maher TM. A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis. Eur Respir J. 2019 Mar 18;53(3):1801992. doi: 10.1183/13993003.01992-2018. Print 2019 Mar.
• Mercer PF, Woodcock HV, Eley JD, Plate M, Sulikowski MG, Durrenberger PF, Franklin L, Nanthakumar CB, Man Y, Genovese F, McAnulty RJ, Yang S, Maher TM, Nicholson AG, Blanchard AD, Marshall RP, Lukey PT, Chambers RC. Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF. Thorax. 2016 Aug;71(8):701-11. doi: 10.1136/thoraxjnl-2015-207429. Epub 2016 Apr 21.

Drugs

Indications