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Transform-UK: A Phase 2 Trial of Tocilizumab in Pulmonary Arterial Hypertension
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A7804 - Transform-UK: A Phase 2 Trial of Tocilizumab in Pulmonary Arterial Hypertension
Author Block: M. Toshner1, A. Church2, L. Harlow3, G. Coghlan4, S. Gibbs5, D. Gor6, J. Hernandez-Sanchez3, D. Kiely7, E. Knightbridge3, J. Suntharalingam8, M. Wilkins5, J. Wort9, S. P. Gaine10, N. W. Morrell11, P. Corris12; 1University of Cambridge, Cambridge, United Kingdom, 2Golden Jubilee Hospital, Glasgow, United Kingdom, 3Papworth Hospital, Cambridge, United Kingdom, 4Royal Free Hosp, London NW3 2QG, United Kingdom, 5Hammersmith Hospital, London, United Kingdom, 6Roche, Welwyn Garden City, United Kingdom, 7Royal Hallamshire Hopsital, Sheffield, United Kingdom, 8Royal United Hospital, Bath, United Kingdom, 9Imperial College, London, United Kingdom, 10Mater Misericordiae Hosp, Dublin 7, Ireland, 11Addenbrookes Hosp, Cambridge CB2 2QQ, United Kingdom, 12Respiratory, Freeman Hospital, Newcastle, United Kingdom.
Introduction An association of inflammation with altered immunity in pulmonary arterial hypertension (PAH) is well established. Preclinical models suggest a central role of the inflammatory cytokine interleukin-6 (IL-6) in disease pathobiology. In addition, patients with idiopathic and heritable PAH have increased levels of circulating IL-6 that predict survival. Transform-UK was designed to test whether the IL-6 receptor antagonist, tocilizumab, is safe and efficacious in patients with group 1 PAH. Methods Transform-UK is an open-label multicentre study of 8mg/kg monthly intravenous (IV) tocilizumab over 6 months in group 1 PAH1. The co-primary endpoints are safety, as defined by the incidence and severity of adverse events, and pulmonary vascular resistance measured during right heart catheterization (RHC). Results Twenty-nine patients (M/F 10/19; mean age 54.9 (SD11.4)) were recruited in total between January 2016 to April 2017. The final end of study visit completed in October 2017 and the last safety visit is due to complete in February 2018. Sixteen patients had idiopathic PAH, 10 connective tissue disease associated PAH (CTD-PAH), and 3 heritable PAH. Six patients were withdrawn prior to drug administration; one chest infection, one exacerbation of co-morbid disease, 4 at baseline RHC. Twenty-three patients received study drug. Drug was discontinued in 4 patients due to serious adverse events (urosepsis, clinical worsening, chest pain and peripheral arterial embolus). Vomiting occurred in one patient and was classified as a suspected unexpected serious adverse reaction. There were no deaths. Hard data lock is scheduled for March 2018 and preliminary results of the study will be available for presentation. Conclusions Transform-UK has successfully completed recruitment of PAH patients to a proof-of-concept trial of tocilizumab in PAH. Preliminary safety data included known and expected complications of tocilizumab and initial efficacy data will be presented. 1 Hernández-Sánchez et al. Clinical trial protocol for TRANSFORM-UK: A therapeutic open-label study of tocilizumab in the treatment of pulmonary arterial hypertension. Pulm Circ. 2018 Jan-Mar;8(1):2045893217735820.
Author Block: M. Toshner1, A. Church2, L. Harlow3, G. Coghlan4, S. Gibbs5, D. Gor6, J. Hernandez-Sanchez3, D. Kiely7, E. Knightbridge3, J. Suntharalingam8, M. Wilkins5, J. Wort9, S. P. Gaine10, N. W. Morrell11, P. Corris12; 1University of Cambridge, Cambridge, United Kingdom, 2Golden Jubilee Hospital, Glasgow, United Kingdom, 3Papworth Hospital, Cambridge, United Kingdom, 4Royal Free Hosp, London NW3 2QG, United Kingdom, 5Hammersmith Hospital, London, United Kingdom, 6Roche, Welwyn Garden City, United Kingdom, 7Royal Hallamshire Hopsital, Sheffield, United Kingdom, 8Royal United Hospital, Bath, United Kingdom, 9Imperial College, London, United Kingdom, 10Mater Misericordiae Hosp, Dublin 7, Ireland, 11Addenbrookes Hosp, Cambridge CB2 2QQ, United Kingdom, 12Respiratory, Freeman Hospital, Newcastle, United Kingdom.
Introduction An association of inflammation with altered immunity in pulmonary arterial hypertension (PAH) is well established. Preclinical models suggest a central role of the inflammatory cytokine interleukin-6 (IL-6) in disease pathobiology. In addition, patients with idiopathic and heritable PAH have increased levels of circulating IL-6 that predict survival. Transform-UK was designed to test whether the IL-6 receptor antagonist, tocilizumab, is safe and efficacious in patients with group 1 PAH. Methods Transform-UK is an open-label multicentre study of 8mg/kg monthly intravenous (IV) tocilizumab over 6 months in group 1 PAH1. The co-primary endpoints are safety, as defined by the incidence and severity of adverse events, and pulmonary vascular resistance measured during right heart catheterization (RHC). Results Twenty-nine patients (M/F 10/19; mean age 54.9 (SD11.4)) were recruited in total between January 2016 to April 2017. The final end of study visit completed in October 2017 and the last safety visit is due to complete in February 2018. Sixteen patients had idiopathic PAH, 10 connective tissue disease associated PAH (CTD-PAH), and 3 heritable PAH. Six patients were withdrawn prior to drug administration; one chest infection, one exacerbation of co-morbid disease, 4 at baseline RHC. Twenty-three patients received study drug. Drug was discontinued in 4 patients due to serious adverse events (urosepsis, clinical worsening, chest pain and peripheral arterial embolus). Vomiting occurred in one patient and was classified as a suspected unexpected serious adverse reaction. There were no deaths. Hard data lock is scheduled for March 2018 and preliminary results of the study will be available for presentation. Conclusions Transform-UK has successfully completed recruitment of PAH patients to a proof-of-concept trial of tocilizumab in PAH. Preliminary safety data included known and expected complications of tocilizumab and initial efficacy data will be presented. 1 Hernández-Sánchez et al. Clinical trial protocol for TRANSFORM-UK: A therapeutic open-label study of tocilizumab in the treatment of pulmonary arterial hypertension. Pulm Circ. 2018 Jan-Mar;8(1):2045893217735820.
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