Preclinical Studies of Omalizumab in Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP)

Johns Hopkins University

Status and phase

Completed

Early Phase 1

Conditions

Nasal Polyps

Chronic Rhinosinusitis With Nasal Polyps

Treatments

Biological: Omalizumab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT04583501

IRB00255799

Details and patient eligibility

About

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.

Full 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.

Enrollment

21 patients

Sex

All

Ages

18 to 100 years old

Volunteers

No 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.