Cargando…

SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma

BACKGROUND: Many patients with severe asthma continue to experience asthma symptoms and exacerbations despite standard-of-care treatment. A substantial proportion of these patients require long-term treatment with oral corticosteroids (OCS), often at high doses, which are associated with considerabl...

Descripción completa

Detalles Bibliográficos
Autores principales: Wechsler, Michael E., Colice, Gene, Griffiths, Janet M., Almqvist, Gun, Skärby, Tor, Piechowiak, Teresa, Kaur, Primal, Bowen, Karin, Hellqvist, Åsa, Mo, May, Garcia Gil, Esther
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550846/
https://www.ncbi.nlm.nih.gov/pubmed/33050928
http://dx.doi.org/10.1186/s12931-020-01503-z
_version_ 1783593053456433152
author Wechsler, Michael E.
Colice, Gene
Griffiths, Janet M.
Almqvist, Gun
Skärby, Tor
Piechowiak, Teresa
Kaur, Primal
Bowen, Karin
Hellqvist, Åsa
Mo, May
Garcia Gil, Esther
author_facet Wechsler, Michael E.
Colice, Gene
Griffiths, Janet M.
Almqvist, Gun
Skärby, Tor
Piechowiak, Teresa
Kaur, Primal
Bowen, Karin
Hellqvist, Åsa
Mo, May
Garcia Gil, Esther
author_sort Wechsler, Michael E.
collection PubMed
description BACKGROUND: Many patients with severe asthma continue to experience asthma symptoms and exacerbations despite standard-of-care treatment. A substantial proportion of these patients require long-term treatment with oral corticosteroids (OCS), often at high doses, which are associated with considerable multiorgan adverse effects, including metabolic disorders, osteoporosis and adrenal insufficiency. Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. In the PATHWAY phase 2b study (NCT02054130), tezepelumab significantly reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma. Several ongoing phase 3 trials (SOURCE, NCT03406078; NAVIGATOR, NCT03347279; DESTINATION, NCT03706079) are assessing the efficacy and safety of tezepelumab in patients with severe, uncontrolled asthma. Here, we describe the design and objectives of SOURCE, a phase 3 OCS-sparing study. METHODS: SOURCE is an ongoing phase 3, multicentre, randomized, double-blind, placebo-controlled study to evaluate the effect of tezepelumab 210 mg administered subcutaneously every 4 weeks on OCS dose reduction in adults with OCS-dependent asthma. The study comprises a 2-week screening and enrolment period, followed by an OCS optimization phase of up to 8 weeks and a 48-week treatment period, which consists of a 4-week induction phase, followed by a 36-week OCS reduction phase and an 8-week maintenance phase. The primary objective is to assess the effect of tezepelumab compared with placebo in reducing the prescribed OCS maintenance dose. The key secondary objective is to assess the effect of tezepelumab on asthma exacerbation rates. Other secondary objectives include the proportion of patients with a reduction in OCS dose (100% or 50% reduction or those receiving < 5 mg) and the effect of tezepelumab on lung function and patient-reported outcomes. CONCLUSIONS: SOURCE is evaluating the OCS-sparing potential of tezepelumab in patients with OCS-dependent asthma. SOURCE also aims to demonstrate that treatment with tezepelumab in patients with severe asthma is associated with reductions in exacerbation rates and improvements in lung function, asthma control and health-related quality of life, while reducing OCS dose. TRIAL REGISTRATION: NCT03406078 (ClinicalTrials.gov). Registered 23 January 2018. https://clinicaltrials.gov/ct2/show/NCT03406078
format Online
Article
Text
id pubmed-7550846
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-75508462020-10-13 SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma Wechsler, Michael E. Colice, Gene Griffiths, Janet M. Almqvist, Gun Skärby, Tor Piechowiak, Teresa Kaur, Primal Bowen, Karin Hellqvist, Åsa Mo, May Garcia Gil, Esther Respir Res Study Protocol BACKGROUND: Many patients with severe asthma continue to experience asthma symptoms and exacerbations despite standard-of-care treatment. A substantial proportion of these patients require long-term treatment with oral corticosteroids (OCS), often at high doses, which are associated with considerable multiorgan adverse effects, including metabolic disorders, osteoporosis and adrenal insufficiency. Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. In the PATHWAY phase 2b study (NCT02054130), tezepelumab significantly reduced exacerbations by up to 71% in adults with severe, uncontrolled asthma. Several ongoing phase 3 trials (SOURCE, NCT03406078; NAVIGATOR, NCT03347279; DESTINATION, NCT03706079) are assessing the efficacy and safety of tezepelumab in patients with severe, uncontrolled asthma. Here, we describe the design and objectives of SOURCE, a phase 3 OCS-sparing study. METHODS: SOURCE is an ongoing phase 3, multicentre, randomized, double-blind, placebo-controlled study to evaluate the effect of tezepelumab 210 mg administered subcutaneously every 4 weeks on OCS dose reduction in adults with OCS-dependent asthma. The study comprises a 2-week screening and enrolment period, followed by an OCS optimization phase of up to 8 weeks and a 48-week treatment period, which consists of a 4-week induction phase, followed by a 36-week OCS reduction phase and an 8-week maintenance phase. The primary objective is to assess the effect of tezepelumab compared with placebo in reducing the prescribed OCS maintenance dose. The key secondary objective is to assess the effect of tezepelumab on asthma exacerbation rates. Other secondary objectives include the proportion of patients with a reduction in OCS dose (100% or 50% reduction or those receiving < 5 mg) and the effect of tezepelumab on lung function and patient-reported outcomes. CONCLUSIONS: SOURCE is evaluating the OCS-sparing potential of tezepelumab in patients with OCS-dependent asthma. SOURCE also aims to demonstrate that treatment with tezepelumab in patients with severe asthma is associated with reductions in exacerbation rates and improvements in lung function, asthma control and health-related quality of life, while reducing OCS dose. TRIAL REGISTRATION: NCT03406078 (ClinicalTrials.gov). Registered 23 January 2018. https://clinicaltrials.gov/ct2/show/NCT03406078 BioMed Central 2020-10-13 2020 /pmc/articles/PMC7550846/ /pubmed/33050928 http://dx.doi.org/10.1186/s12931-020-01503-z Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Study Protocol
Wechsler, Michael E.
Colice, Gene
Griffiths, Janet M.
Almqvist, Gun
Skärby, Tor
Piechowiak, Teresa
Kaur, Primal
Bowen, Karin
Hellqvist, Åsa
Mo, May
Garcia Gil, Esther
SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma
title SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma
title_full SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma
title_fullStr SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma
title_full_unstemmed SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma
title_short SOURCE: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma
title_sort source: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550846/
https://www.ncbi.nlm.nih.gov/pubmed/33050928
http://dx.doi.org/10.1186/s12931-020-01503-z
work_keys_str_mv AT wechslermichaele sourceaphase3multicentrerandomizeddoubleblindplacebocontrolledparallelgrouptrialtoevaluatetheefficacyandsafetyoftezepelumabinreducingoralcorticosteroiduseinadultswithoralcorticosteroiddependentasthma
AT colicegene sourceaphase3multicentrerandomizeddoubleblindplacebocontrolledparallelgrouptrialtoevaluatetheefficacyandsafetyoftezepelumabinreducingoralcorticosteroiduseinadultswithoralcorticosteroiddependentasthma
AT griffithsjanetm sourceaphase3multicentrerandomizeddoubleblindplacebocontrolledparallelgrouptrialtoevaluatetheefficacyandsafetyoftezepelumabinreducingoralcorticosteroiduseinadultswithoralcorticosteroiddependentasthma
AT almqvistgun sourceaphase3multicentrerandomizeddoubleblindplacebocontrolledparallelgrouptrialtoevaluatetheefficacyandsafetyoftezepelumabinreducingoralcorticosteroiduseinadultswithoralcorticosteroiddependentasthma
AT skarbytor sourceaphase3multicentrerandomizeddoubleblindplacebocontrolledparallelgrouptrialtoevaluatetheefficacyandsafetyoftezepelumabinreducingoralcorticosteroiduseinadultswithoralcorticosteroiddependentasthma
AT piechowiakteresa sourceaphase3multicentrerandomizeddoubleblindplacebocontrolledparallelgrouptrialtoevaluatetheefficacyandsafetyoftezepelumabinreducingoralcorticosteroiduseinadultswithoralcorticosteroiddependentasthma
AT kaurprimal sourceaphase3multicentrerandomizeddoubleblindplacebocontrolledparallelgrouptrialtoevaluatetheefficacyandsafetyoftezepelumabinreducingoralcorticosteroiduseinadultswithoralcorticosteroiddependentasthma
AT bowenkarin sourceaphase3multicentrerandomizeddoubleblindplacebocontrolledparallelgrouptrialtoevaluatetheefficacyandsafetyoftezepelumabinreducingoralcorticosteroiduseinadultswithoralcorticosteroiddependentasthma
AT hellqvistasa sourceaphase3multicentrerandomizeddoubleblindplacebocontrolledparallelgrouptrialtoevaluatetheefficacyandsafetyoftezepelumabinreducingoralcorticosteroiduseinadultswithoralcorticosteroiddependentasthma
AT momay sourceaphase3multicentrerandomizeddoubleblindplacebocontrolledparallelgrouptrialtoevaluatetheefficacyandsafetyoftezepelumabinreducingoralcorticosteroiduseinadultswithoralcorticosteroiddependentasthma
AT garciagilesther sourceaphase3multicentrerandomizeddoubleblindplacebocontrolledparallelgrouptrialtoevaluatetheefficacyandsafetyoftezepelumabinreducingoralcorticosteroiduseinadultswithoralcorticosteroiddependentasthma