Cargando…
Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial
BACKGROUND: Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. Th...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359732/ https://www.ncbi.nlm.nih.gov/pubmed/37483544 http://dx.doi.org/10.1016/j.eclinm.2023.102076 |
_version_ | 1785075952076718080 |
---|---|
author | Zhang, Yuan Yan, Bing Shen, Shen Song, Xicheng Jiang, Yan Shi, Li Zhao, Changqing Yang, Yi Jiang, Luyun Li, Jiping Ye, Jing Liu, Jinfeng Wan, Lijia Yang, Yucheng Chen, Jianjun Liu, Feng Su, Lizhong Xu, Yu Tan, Guolin Yu, Shaoqing Zhang, Yu Wang, Lin Liu, Shengyang Yan, Hongyue Liu, Wei Chen, Bo Wang, Chengshuo Zhang, Luo |
author_facet | Zhang, Yuan Yan, Bing Shen, Shen Song, Xicheng Jiang, Yan Shi, Li Zhao, Changqing Yang, Yi Jiang, Luyun Li, Jiping Ye, Jing Liu, Jinfeng Wan, Lijia Yang, Yucheng Chen, Jianjun Liu, Feng Su, Lizhong Xu, Yu Tan, Guolin Yu, Shaoqing Zhang, Yu Wang, Lin Liu, Shengyang Yan, Hongyue Liu, Wei Chen, Bo Wang, Chengshuo Zhang, Luo |
author_sort | Zhang, Yuan |
collection | PubMed |
description | BACKGROUND: Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP. METHODS: A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398. FINDINGS: Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were −2.1 (95% CI −2.9, −1.4; p < 0.0001) and −0.9 (95% CI −1.4, −0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] −7.6, [−9.4, −5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] −37%, [−47%, −28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (−2.6 [95% CI −3.5, −1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (−19.1 [95% CI −29.8, −8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related. INTERPRETATION: These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP. FUNDING: KeyMed Biosciences (Chengdu) Limited. |
format | Online Article Text |
id | pubmed-10359732 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-103597322023-07-22 Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial Zhang, Yuan Yan, Bing Shen, Shen Song, Xicheng Jiang, Yan Shi, Li Zhao, Changqing Yang, Yi Jiang, Luyun Li, Jiping Ye, Jing Liu, Jinfeng Wan, Lijia Yang, Yucheng Chen, Jianjun Liu, Feng Su, Lizhong Xu, Yu Tan, Guolin Yu, Shaoqing Zhang, Yu Wang, Lin Liu, Shengyang Yan, Hongyue Liu, Wei Chen, Bo Wang, Chengshuo Zhang, Luo eClinicalMedicine Articles BACKGROUND: Severe eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) remains the most relapsed subtype of uncontrolled CRSwNP. CM310, a humanised anti-interleukin (IL)-4 receptor alpha monoclonal antibody, inhibits IL-4 and IL-13 signaling which underlying eosinophilic inflammation. This study aims to evaluate the efficacy and safety of CM310 in patients with severe ECRSwNP. METHODS: A multicentre, randomised, double-blind, and placebo-controlled phase 2 clinical trial was conducted. 56 eligible adult patients with severe ECRSwNP were randomised 1:1 to receive subcutaneously either CM310 (300 mg) or placebo every 2 weeks under the background therapy of mometasone furoate nasal spray (MFNS) for 16 weeks, with 8 weeks of follow-up. Coprimary endpoints included the changes from baseline in nasal polyp score (NPS) and nasal congestion score (NCS) at week 16. Key secondary endpoints included sinus Lund-Mackay CT score, change in sinus volume occupied by disease, University of Pennsylvania Smell Identification Test score, 22-item Sino-nasal Outcome Test score, and total symptom score. Safety, pharmacodynamics, and changes in type 2 inflammation biomarkers were assessed. This study is registered with ClinicalTrials.gov, NCT04805398. FINDINGS: Between April 6, 2021, and March 18, 2022, 27 patients respectively in both the CM310 and placebo groups completed the study. Findings suggested that CM310 improved the coprimary efficacy endpoints of decreasing nasal polyp size and alleviating nasal congestion compared with the placebo. Least squares (LS) mean differences (CM310 vs placebo) of change from baseline in NPS and NCS at week 16 were −2.1 (95% CI −2.9, −1.4; p < 0.0001) and −0.9 (95% CI −1.4, −0.5; p < 0.0001), respectively. Sinus CT scan revealed that Lund-Mackay CT score (LS mean difference [95% CI] −7.6, [−9.4, −5.8]; p < 0.0001) and sinus volume occupied by disease (LS mean difference [95% CI] −37%, [−47%, −28%]; p < 0.0001) were significantly improved with CM310 compared with placebo. In addition, CM310 significantly relieved the daily symptoms of patients with CRSwNP and improved their quality of life reflected by the improvements in the TSS (−2.6 [95% CI −3.5, −1.6]), UPSIT (10.4 [95% CI 6.8, 14.0]) and SNOT-22 score (−19.1 [95% CI −29.8, −8.5]). Compared with placebo, CM310 administration significantly reduced type 2-related biomarkers including the serum TARC and total IgE, and tissue eosinophils. The most common adverse events were upper respiratory tract infection, blood cholesterol increased, and tinnitus, but none were considered drug-related. INTERPRETATION: These findings support CM310 as an effective additional treatment option to the standard of care in patients with severe ECRSwNP. FUNDING: KeyMed Biosciences (Chengdu) Limited. Elsevier 2023-07-05 /pmc/articles/PMC10359732/ /pubmed/37483544 http://dx.doi.org/10.1016/j.eclinm.2023.102076 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Articles Zhang, Yuan Yan, Bing Shen, Shen Song, Xicheng Jiang, Yan Shi, Li Zhao, Changqing Yang, Yi Jiang, Luyun Li, Jiping Ye, Jing Liu, Jinfeng Wan, Lijia Yang, Yucheng Chen, Jianjun Liu, Feng Su, Lizhong Xu, Yu Tan, Guolin Yu, Shaoqing Zhang, Yu Wang, Lin Liu, Shengyang Yan, Hongyue Liu, Wei Chen, Bo Wang, Chengshuo Zhang, Luo Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial |
title | Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial |
title_full | Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial |
title_fullStr | Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial |
title_full_unstemmed | Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial |
title_short | Efficacy and safety of CM310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (CROWNS-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial |
title_sort | efficacy and safety of cm310 in severe eosinophilic chronic rhinosinusitis with nasal polyps (crowns-1): a multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359732/ https://www.ncbi.nlm.nih.gov/pubmed/37483544 http://dx.doi.org/10.1016/j.eclinm.2023.102076 |
work_keys_str_mv | AT zhangyuan efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT yanbing efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT shenshen efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT songxicheng efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT jiangyan efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT shili efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT zhaochangqing efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT yangyi efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT jiangluyun efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT lijiping efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT yejing efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT liujinfeng efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT wanlijia efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT yangyucheng efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT chenjianjun efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT liufeng efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT sulizhong efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT xuyu efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT tanguolin efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT yushaoqing efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT zhangyu efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT wanglin efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT liushengyang efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT yanhongyue efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT liuwei efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT chenbo efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT wangchengshuo efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial AT zhangluo efficacyandsafetyofcm310insevereeosinophilicchronicrhinosinusitiswithnasalpolypscrowns1amulticentrerandomiseddoubleblindplacebocontrolledphase2clinicaltrial |