Chronic RhinosinusitisPhase 2NCT01066104
Subcutaneous Omalizumab for Treatment of Chronic Rhinosinusitis With Nasal Polyposis
A Phase 2 study testing Xolair (omalizumab) in people with Chronic Rhinosinusitis and Nasal Polyps, run by Massachusetts General Hospital at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Rhinosinusitis, Nasal Polyps
- What is being tested?
- Xolair (omalizumab)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2009to Jul 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects will be male or female and 18 years of age or older.
- Females of childbearing potential will use approved contraception, defined as the use of hormonal (oral, injectable, or implantable) or barrier-method contraceptives, intrauterine device, or history of bilateral tubal ligation. Women who have undergone a total hysterectomy or are two years post-menopausal will also be eligible.
- Subjects must meet the criteria for CRS, namely they must have (1) at least two major criteria (facial pain/pressure or headache, nasal congestion, anterior or posterior nasal drainage, hyposmia/anosmia) for at least 3 consecutive months; (2) an abnormal sinus CT scan in at least two sinus areas documented within 3 months of entry or endoscopic evidence of disease.
- Subjects must have bilateral polypoid disease demonstrated either by CT or endoscopy with evidence of nasal polyps or polypoid mucosa on examination in at least two of the following areas: right maxillary sinus, left maxillary sinus, right anterior ethmoid sinus, left anterior ethmoid sinus plus a minimal polyp/polypoid score of 4 on the baseline rhinoscopic examination. (Nasal polyps are defined as discreet polyps visible in the middle meatus area.)
- Evidence or history of positive skin test or in vitro reactivity to a perennial aeroallergen.
- Subjects must meet the study drug-dosing table eligibility criteria (serum IgE level ≥ 30 to ≤ 1500 IU/mL and body weight ≥ 30 to ≤ 150 kg).
- Subjects must have a minimum total symptom score of 5 (range of scores 0-15) at baseline.
Who cannot join
- Females who are pregnant or nursing, or females of childbearing potential not using approved contraception, defined as the use of hormonal (oral, injectable, or implantable) or barrier-method contraceptives, intrauterine device, or history of bilateral tubal ligation.
- Subjects who do not meet the clinical criteria for Xolair (omalizumab)
- Subjects who are taking a beta blocker.
- Known sensitivity to Xolair (omalizumab).
- Subjects who have evidence of acute bacterial exacerbation of rhinosinusitis requiring antibiotic therapy manifesting as gross purulent drainage on physical examination or untreated air/fluid level on sinus CT scan.
- Subjects who have received antibiotics within 3 weeks of the screening visit.
Show all 16Show fewer
- Subjects with uncontrolled moderate to severe asthma who have experienced a recent exacerbation requiring use of systemic steroids burst within 6 weeks of study enrollment. Subjects who are receiving a maintenance dose of Prednisone of 5 mg/day or less will be allowed provided the dose of Prednisone is not changed during the study.
- Subjects with a history of uncontrolled recurrent epistaxis within the past 6 weeks.
- Subjects with a history of hypogammaglobulinemia, cystic fibrosis, bronchiectasis, immotile cilia syndrome, systemic granulomatous disease, malignancy (or strong family history of malignancy), or history of recent cocaine use.
- Cigarette smoking in the past 3 years.
- Subjects with other serious medical problems, such as Grade III/IV cardiac problems as defined by the New York Heart Association Criteria within 6 months of study, severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal or liver disease, infection with HIV or other active uncontrolled infection). Subjects who have had a major surgery within 3 months of the screening visit.
- Subjects with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
- Subjects with alcohol or drug abuse/dependence within the past 3 months.
- Subjects with persistent abnormalities of hepatic, renal or hematologic function, defined as the following: total bilirubin, SGOT and SGPT > 1.5 x upper limit of normal, creatinine > 2.0 x upper limit of normal, absolute neutrophil count < 1.5 x 109/L, platelets < 100 x 109/L.
- Subjects who have used oral or systemic steroid burst within 6 weeks of study enrollment.
- Use of any other investigational agent in the 30 days prior to enrollment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
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).
Read the 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:
- 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.
- Total symptom score (TSS) recorded daily. CRS Facial Pain/Headache questionnaire at each visit.
- 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
- Conditions
- Chronic Rhinosinusitis, Nasal Polyps
- Being tested
- Xolair placebo, Xolair (omalizumab)
- Medical subject headings
- Nasal Polyps
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Xolair placeboDrug
Also called omalizumab placebo
two to four weeks (dosage and frequency will be determined based on patient weight and IgE level)
Xolair (omalizumab)Drug
Also called omalizumab
two to four weeks (dosage and frequency will be determined based on patient weight and IgE level)
| Study group | Role | What they receive |
|---|---|---|
| Xolair placebo | Placebo comparator | 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. Receives: Drug: Xolair placebo |
| Xolair (omalizumab) | Active comparator | 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. Receives: Drug: Xolair (omalizumab) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective (a) the Effect on Polypoid Mucosal Thickening in the Anterior Ethmoid and Maxillary Sinuses as Measured on Sinus CT Scan.
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.
Measured: 4 months
Secondary outcomes (1)
Objective (b) the Effect on Volume of Polypoid Mucosal Tissue in the Nose and Sinuses on Rhinoscopic Examination.
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
- Polyp in middle meatus, not reaching below the inferior border of the middle turbinate
- Polyp reaching below the inferior border of the middle turbinate but not touching the inferior turbinate
- Polyp reaching below the inferior border of the middle turbinate and touching the inferior turbinate
- Polyp reaching to or below the lower border of the inferior turbinate
Range: minimum 0 (better outcome), maximum 8 (worse outcome)
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2010 (estimated)
- Study startDec 2009
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic RhinosinusitisStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Ellen Dutta, MD, Massachusetts General Hospital
- Investigators
- Ellen J Dutta, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01066104
- Sponsor's protocol ID
- 2009P001325
- Status last verified
- May 2017
- First submitted
- 8 Feb 2010
- Last updated
- 14 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Subcutaneous Omalizumab for Treatment of Chronic Rhinosinusitis With Nasal Polyposis
- ClinicalTrials.gov ID
- NCT01066104
- Acronym / sponsor ID
- 2009P001325
- Conditions
- Chronic Rhinosinusitis, Nasal Polyps
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Dec 2009
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 10 Feb 2010 (estimated)
- Results
- Posted 19 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- Total symptom score (TSS) recorded daily. CRS Facial Pain/Headache questionnaire at each visit.
- 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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Xolair placebo | Placebo comparator | Drug: Xolair placeboXolair 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. |
| Xolair (omalizumab) | Active comparator | Drug: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects will be male or female and 18 years of age or older.
- Females of childbearing potential will use approved contraception, defined as the use of hormonal (oral, injectable, or implantable) or barrier-method contraceptives, intrauterine device, or history of bilateral tubal ligation. Women who have undergone a total hysterectomy or are two years post-menopausal will also be eligible.
- Subjects must meet the criteria for CRS, namely they must have (1) at least two major criteria (facial pain/pressure or headache, nasal congestion, anterior or posterior nasal drainage, hyposmia/anosmia) for at least 3 consecutive months; (2) an abnormal sinus CT scan in at least two sinus areas documented within 3 months of entry or endoscopic evidence of disease.
- Subjects must have bilateral polypoid disease demonstrated either by CT or endoscopy with evidence of nasal polyps or polypoid mucosa on examination in at least two of the following areas: right maxillary sinus, left maxillary sinus, right anterior ethmoid sinus, left anterior ethmoid sinus plus a minimal polyp/polypoid score of 4 on the baseline rhinoscopic examination. (Nasal polyps are defined as discreet polyps visible in the middle meatus area.)
- Evidence or history of positive skin test or in vitro reactivity to a perennial aeroallergen.
Key exclusion criteria (16 listed)
- Females who are pregnant or nursing, or females of childbearing potential not using approved contraception, defined as the use of hormonal (oral, injectable, or implantable) or barrier-method contraceptives, intrauterine device, or history of bilateral tubal ligation.
- Subjects who do not meet the clinical criteria for Xolair (omalizumab)
- Subjects who are taking a beta blocker.
- Known sensitivity to Xolair (omalizumab).
- Subjects who have evidence of acute bacterial exacerbation of rhinosinusitis requiring antibiotic therapy manifesting as gross purulent drainage on physical examination or untreated air/fluid level on sinus CT scan.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Xolair placeboAlso: omalizumab placebotwo to four weeks (dosage and frequency will be determined based on patient weight and IgE level) | Drug | Xolair placebo |
| Xolair (omalizumab)Also: omalizumabtwo to four weeks (dosage and frequency will be determined based on patient weight and IgE level) | Drug | Xolair (omalizumab) |
Primary outcome
Objective (a) the Effect on Polypoid Mucosal Thickening in the Anterior Ethmoid and Maxillary Sinuses as Measured on Sinus CT Scan.
Time frame: 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.
1 secondary outcome
Objective (b) the Effect on Volume of Polypoid Mucosal Tissue in the Nose and Sinuses on Rhinoscopic Examination.
Time frame: 4 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ellen J Dutta, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Xolair (omalizumab) in people with Chronic Rhinosinusitis and Nasal Polyps, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective (a) the Effect on Polypoid Mucosal Thickening in the Anterior Ethmoid and Maxillary Sinuses as Measured on Sinus CT Scan. (time frame: 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2017.