Clinical trial NCT04583501: Preclinical Studies of Omalizumab in Chronic Rhinosinusitis With Nasal Polyposis
Official title: Preclinical Studies of Omalizumab in Chronic Rhinosinusitis With Nasal Polyposis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Chronic Rhinosinusitis With Nasal Polyps
Nasal Polyps
Keywords: Chronic Rhinosinusitis with Nasal Polyps
eosinophilic nasal polyposis
nasal polyps
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2020-10-12
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: IgE tissue compartment distribution in nasal polyps as assessed by quantitative IgE expression
timeFrame: 1 year
measure: Messenger ribonucleic acid (mRNA) expression
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Jean Kim, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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