Study on Biomarkers to Predict the Efficacy of IL-4R Monoclonal Antibody for Chronic Rhino-sinusitis With Polyps

Study Overview
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Brief Summary
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The prevalence of chronic rhinosinusitis in China is about 8%, and some patients still suffer from recurrences after surgery and drug treatment. Monoclonal antibody is considered to be a new drug strategy that can significantly improve the control rate of such patients, but there is a lack of markers to guide the selection of monoclonal antibodies. The price of monoclonal antibody is expensive, which calls for screening markers for predicting the efficacy of monoclonal antibody and precisely implementing this treatment strategy. In addition, it can also improve the quality of life of patients and reduce the social and economic burden. Beijing Tongren Hospital, Capital Medical University recently completed a randomized, double-blind, placebo-controlled, phase II clinical study which included multiple subcutaneous administration of CM310 recombinant humanized monoclonal antibody injection in patients with chronic sinusitis and nasal polyps to evaluate the efficacy and safety as well as the pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy(NCT04805398). The therapeutic target of CM310 recombinant humanized monoclonal antibody injection is IL-4R. The unblinded data showed significant differences in the efficacy of the subjects and we started the investigator-initiate trial (IIT) study aiming at investigating the remaining samples of the project and carrying out a biomarker study to screen and predict the efficacy of IL-4R monoclonal antibody.

Detailed Description
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The prevalence of chronic rhinosinusitis in China is about 8%, and some patients still suffer from recurrences after surgery and drug treatment. Monoclonal antibody is considered to be a new drug strategy that can significantly improve the control rate of such patients, but there is a lack of markers to guide the selection of monoclonal antibodies. The price of monoclonal antibody is expensive, which calls for screening markers for predicting the efficacy of monoclonal antibody and precisely implementing this treatment strategy. In addition, it can also improve the quality of life of patients and reduce the social and economic burden. Beijing Tongren Hospital, Capital Medical University recently completed a randomized, double-blind, placebo-controlled, phase II clinical study which included multiple subcutaneous administration of CM310 recombinant humanized monoclonal antibody injection in patients with chronic sinusitis and nasal polyps to evaluate the efficacy and safety as well as the pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy(NCT04805398, detailed in https://clinicaltrials.gov/ct2/show/NCT04805398). The therapeutic target of CM310 recombinant humanized monoclonal antibody injection is IL-4R. The unblinded data showed significant differences in the efficacy of the subjects and we started the IIT study aiming at investigating the remaining samples of the project and carrying out a biomarker study to screen and predict the efficacy of IL-4R monoclonal antibody. The biomarker levels between IL-4R responders(Defined as Nasal Polyps Score (NPS)>1 at 16 months after subcutaneously CM310) and IL-4R nonresponders (Defined as Nasal NPS≤1 at 16 months after subcutaneously CM310)were compared. The biomarker levels between IL-4R and control groups were also compared.

Official Title
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Study on Biomarkers to Predict the Efficacy of IL-4R Monoclonal Antibody（CM310） for Chronic Rhino-sinusitis With Polyps

Conditions
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Chronic Rhino-sinusitis, IL-4R, Monoclonal Antibody, Biomarker

Intervention / Treatment
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* Other: IL-4R
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients enrolled in NCT04805398. Exclusion Criteria: Patients not enrolled in NCT04805398.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| IL-4R responders<br>IL-4R was injected subcutaneously. Base line and treatment end point nasal polyp score were compared and NPS >1. | Other: IL-4R<br>* IL-4R was injected subcutaneously.<br>|
| IL-4R nonresponders<br>IL-4R was injected subcutaneously. Base line and treatment end point nasal polyp score were compared and NPS ≤1. | Other: IL-4R<br>* IL-4R was injected subcutaneously.<br>|
| Controls<br>Placebo was injected subcutaneously. | Other: Placebo<br>* Placebo was injected subcutaneously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Base line sirius red staining and immunopathological staining | Base line sirius red staining and immunopathological staining | Base line | 
| End point sirius red staining and immunopathological staining | End point sirius red staining and immunopathological staining | at Week 16 |