Subcutaneous Omalizumab for Treatment of Chronic Rhinosinusitis With Nasal Polyposis

Phase 2

Completed

Conditions: Chronic Rhinosinusitis
Nasal Polyps

Interventions: Drug: Xolair (omalizumab)
Drug: Xolair placebo

Registration Number: NCT01066104

Lead Sponsor: Massachusetts General Hospital

Brief Summary: The investigators are doing this research study to learn more about a drug called Xolair (omalizumab). The investigators want to see if it is an effective treatment for chronic rhinosinusitis (CRS). Specifically, the investigators want to see whether Xolair will make nasal polyps smaller and less thick, and relieve symptoms in people with CRS. Polyps are abnormal growths of tissue that can grow in the lining of your sinuses (the inside of your nose). The investigators also want to find out if it is safe to use (whether it causes side effects).

Detailed Description: Title of study: Subcutaneous Xolair (omalizumab) for treatment of chronic rhinosinusitis with nasal polyposis (CRS/NP)

Objectives: To compare the efficacy of subcutaneous Xolair (omalizumab) to placebo in treatment of CRS/NP in terms of: (a) the effect on polypoid mucosal thickening in the anterior ethmoid and maxillary sinuses as measured on sinus CT scan, (b) the effect on volume of polypoid mucosal tissue in the nose and sinuses on rhinoscopic examination, and (c) the effect on CRS symptoms as measured by total symptom score.

Study Rationale: Chronic rhinosinusitis (CRS) is a persistent inflammatory condition with periodic flares, affecting 14% of the United States population with an estimated annual health care expenditure of $3.4 billion. CRS patients with nasal polyposis (NP) are the most difficult to treat and the most likely to undergo sinus surgery. Tissue eosinophilia is the hallmark feature and is associated with specific IgE to inhalants, elevated total serum immunoglobulin E (IgE), and peripheral eosinophilia. Omalizumab is a humanized monoclonal antibody that binds to the Fc portion of IgE. Omalizumab treatment reduces peripheral eosinophilia and prevents nasal tissue eosinophilia. Endoscopic NP severity directly correlates with total serum IgE levels, and anti-IgE therapy in the postpolypectomy management of atopic asthmatic patients may reduce the severity of NP recurrence. In a patient with CRS/NP with asthma treated with omalizumab, symptoms were relieved, and MRI showed resolution of nasal mucosa swelling and reduction of polypoid swelling and inflammation of the paranasal sinuses. We hypothesize that subcutaneous Xolair (omalizumab) treatment will reduce the size of nasal polyps and/or sinus polypoid thickening and relieve CRS symptoms in patients with CRS/NP.

Methodology:

Xolair (omalizumab) or placebo injections every 2-4 weeks for 5 months. Procedures will include:

1. Quantification of polypoid mucosal thickening in the anterior ethmoid and maxillary sinuses on sinus CT scan (primary outcome variable) on Day 0 and on Day 140.

2. Total symptom score (TSS) recorded daily. CRS Facial Pain/Headache questionnaire at each visit.

3. Rhinoscopic evaluation during screening and on Days 28, 84 and 140. Number of centers \& patients: Single center. 30 patients (15 per treatment group).

Population: Outpatient male or female, 18 years of age or older, with CRS/NP, without uncontrolled moderate to severe asthma.

Investigational drug: Xolair (omalizumab), dosage and frequency to be determined based on patient's weight and total IgE level, administered by subcutaneous injection.

Reference therapy: Placebo of similar volume and frequency, administered by subcutaneous injection

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Xolair (omalizumab)	Xolair (omalizumab)	Xolair (omalizumab) 150-375 mg is administered subcutaneously (SC) every 2 or 4 weeks depending on the patient's baseline serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg). Doses of more than 150 mg are divided among more than one injection site to limit injections to not more than 150 mg per site.
Xolair placebo	Xolair placebo	Xolair placebo 150-375 mg is administered subcutaneously (SC) every 2 or 4 weeks depending on the patient's baseline serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg) ). Doses of more than 150 mg are divided among more than one injection site to limit injections to not more than 150 mg per site.

Primary Outcome Measures

Name	Time	Method
Objective (a) the Effect on Polypoid Mucosal Thickening in the Anterior Ethmoid and Maxillary Sinuses as Measured on Sinus CT Scan.	4 months	Improvement is defined as any decrease in sinus CT scores at end of study. Quantification of polypoid mucosal thickening in the anterior ethmoid and maxillary sinuses on sinus CT scan (primary outcome variable): A sinus CT scan will be performed on Day 0 and repeated on Day 112. The CT scans will be performed with consistent orientation of the patient's head and landmarks to assure that both the pretreatment and posttreatment scans are done with identical orientation and sections. The CT scans will be scored using the established scoring system known as the Zinreich modification of the Lund Mackay scoring system.. As an exploratory measure, a 3-dimensional scoring system developed with the radiology department of Massachusetts General Hospital may also be used.

Secondary Outcome Measures

Name	Time	Method
Objective (b) the Effect on Volume of Polypoid Mucosal Tissue in the Nose and Sinuses on Rhinoscopic Examination.	4 months	Improvement is defined as any reduction in the total nasal polyp score. Using rhinoscopic evaluation, Nasal Polyp Score will be assessed on the right and on the left, and added together. Scoring system: Score Definition 0 No polyps 1. Polyp in middle meatus, not reaching below the inferior border of the middle turbinate 2. Polyp reaching below the inferior border of the middle turbinate but not touching the inferior turbinate 3. Polyp reaching below the inferior border of the middle turbinate and touching the inferior turbinate 4. Polyp reaching to or below the lower border of the inferior turbinate Range: minimum 0 (better outcome), maximum 8 (worse outcome)