CRSwNP: Preclinical Studies of Omalizumab in Chronic Rhinosinusitis With Nasal Polyposis

Sponsor

Johns Hopkins University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04583501

Collaborator

Genentech, Inc. (Industry)

Enrollment

Locations

Arm

24.5

Anticipated Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this study is to examine the mechanism of action of omalizumab in ex vivo tissue culture of whole human nasal polyps from patients with chronic rhino sinusitis with nasal polyposis (CRSwNP), such that specific molecular markers of inflammation can be identified.

Condition or Disease	Intervention/Treatment	Phase
Chronic Rhinosinusitis With Nasal Polyps Nasal Polyps	Biological: Omalizumab	Early Phase 1

Detailed Description

Objectives:

Aim 1. The investigation will identify the specific tissue compartment distribution of immunoglobulin E (IgE) expression within human nasal polyps. Colocalization studies will examine functional interaction of IgE with effector cells.

Aim 2. The investigation will examine the direct effect of omalizumab on expression of Type 2, 1, and 3 inflammatory pathways in human nasal polyp tissue from phenotypically characterized chronic rhinosinusitis with nasal polyposis (CRSwNP) patients.

Study Rationale: Human nasal polyps express high local tissue IgE. However, the tissue distribution, cellular location and functional consequence of IgE accumulation within the polyp tissue is not known. Phase 3 studies of omalizumab demonstrated efficacy, with responders. However, the reason for non-responder outcomes in a subset of CRSwNP patients was not understood. Therefore, the goal of this study is to examine the mechanism of action of omalizumab in CRSwNP, such that specific responders for this treatment can be identified and therapy can be optimally directed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

8 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

Preclinical Studies of Omalizumab in Chronic Rhinosinusitis With Nasal Polyposis

Actual Study Start Date :

Dec 15, 2020

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Omalizumab Ex vivo exposure of excised human surgical polyp tissue to omalizumab.	Biological: Omalizumab Omalizumab will used as dose comparable to to 0.016 mg/kg/IU in serum.

Arm

Intervention/Treatment

Experimental: Omalizumab

Ex vivo exposure of excised human surgical polyp tissue to omalizumab.

Biological: Omalizumab

Omalizumab will used as dose comparable to to 0.016 mg/kg/IU in serum.

Outcome Measures

Primary Outcome Measures

IgE tissue compartment distribution in nasal polyps as assessed by quantitative IgE expression [1 year]
Quantitative IgE Expression within these cellular compartments will be measured by immunohistochemistry.
Messenger ribonucleic acid (mRNA) expression [1 year]
mRNA expression will be analyzed using high throughput RNA sequencing to determine the pattern of inflammatory gene expression.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Sinonasal inflammation for greater than 12 weeks which include at least 2 of the following symptoms: nasal obstruction/congestion, nasal discharge (anterior or posterior), facial pressure/pain, reduction of sense of smell
Confirmation of the clinical symptoms by (2a) CT scan evidence of paranasal sinus mucosal inflammation, and/or (2b) endoscopic exam evidence of purulence from the sinuses or ostiomeatal complex
Presence of nasal polyps seen on endoscopic exam or sinus CT scan
Adults from age of 18-100 will be eligible
All potential participants will be required to sign an Institutional Review Board (IRB) approved research consent form.

Exclusion Criteria:

Children under the age of 18 will be excluded
No pregnant or lactating females, prisoners, mentally disabled, or persons unable to give informed consent will be contemplated for inclusion.
The subject groups will also exclude those with disease secondary to a clearly defined anatomic process, such as facial trauma, and obstruction due to sinonasal neoplasm.
To eliminate confounding variables in our ex vivo experimental studies, any subject with a history of exposure to oral or systemic IV glucocorticoids within 2 weeks of surgery or any immunomodulatory biologics will be excluded. These include, but are not limited to systemic treatment with biologics omalizumab, dupilumab, mepolizumab, benralizumab, reslizumab, or rituximab.