A Phase 2 interventional study of Benralizumab and Placebo in Chronic Rhinosinusitis (Diagnosis), Nasal Polyps and Eosinophilia, sponsored by Johns Hopkins University. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2021-02-11.
Sponsored by Johns Hopkins University · Phase 2, Interventional, and Treatment
Benralizumab will be used in a placebo controlled randomized study to treat severe chronic rhinosinusitis with nasal polyps
Chronic rhinosinusitis (CRS) has a prevalence of more than 10% in the United States and Europe and is associated with several co-morbidities including asthma, acute infection, and obstructive sleep apnea. There are principally two forms of CRS namely with and without nasal polyps. CRS with nasal polyps (CRSwNP) in particular can be a severe and debilitating disease resulting in significant morbidity, complete anosmia, headaches, missed work, and hospitalizations. Not uncommonly, patients require chronic oral corticosteroids, multiple courses of antibiotics, and repeated surgical polypectomies to control participants' disease. Total health care expenditure for CRS (which includes both with and without polyps) is more than $60 billion annually in the United States accounting for as much as 5% of the total US health care budget. Annual direct and indirect costs to treat CRS in Europe is estimated to be similar to this amount but data is limited.
For CRSwNP patients suffering with severe and recurrent nasal polyps there are few treatment options. High dose topical nasal steroids and repeated surgical procedures do not halt progression in many patients. Allergen immunotherapy is often non-curative in this population. Similarly, due to the fact that CRSwNP is not exclusively an Immunoglobulin E (IgE) driven process, omalizumab was shown to have mixed benefit in this population. Likewise, omalizumab resulted in no reduction in polyp size among patients with Aspirin Exacerbated Respiratory Disease (AERD).
More typically chronic nasal polyp disease is an eosinophil mediated process. Patients with demonstrated elevations in serum and mucosal eosinophils tend to have more severe disease and higher nasal polyp recurrence rates. Clinical researchers have begun to recognize this connection. A recent Phase II study in Europe showed a reduction in polyp burden using mepolizumab anti-Interleukin (IL) 5 monoclonal antibody. Benralizumab which targets IL-5 receptor signaling has been shown to have powerful apoptotic effects on eosinophils and may likely prove to be even more efficacious. Because of its unique mechanism of action, benralizumab may have a profound impact on reducing mucosal eosinophils resulting in great benefit to patients suffering with severe nasal polyps refractory to standard treatment.
Benralizumab has been shown to be efficacious treating severe asthmatics with eosinophilia. The unique mechanism of action of benralizumab targets the IL-5 receptor leading to degradation of signaling and apoptosis. This direct effect on eosinophils leads to reduction of proinflammatory processes in the asthmatic airways among those with elevated eosinophil counts. While many subjects with allergic asthma do indeed have concomitant local and systemic elevations in eosinophils, the primary driver of inflammation in allergic asthmatics is IgE and IL-4. Allergen immunotherapy and anti-IgE therapy (omalizumab) has long been known to be effective in these atopic individuals. However, a significant portion of non-asthmatics respond poorly to these IgE targeted therapies.
In a similar manner, chronic rhinosinusitis with nasal polyps (CRSwNP) is a disease often associated with atopy and propagated by IgE/IL-4 mediated inflammation. However, more than 50% of patients with CRSwNP have no evidence of allergen sensitivity. Nasal and sinus inflammation in these non-atopic individuals is often characterized by IL-5 upregulation, eosinophilia, leukotrienes, and more severe polyps. These individuals tend to have more aggressive disease requiring frequent surgeries, high dose intranasal budesonide irrigation, and oral steroids yet the polyps more often than not are persistent and may return post surgery. In a subset of patients, concomitant aspirin sensitivity can be managed with aspirin desensitization, however this approach is not always effective and can also be cumbersome. A more universal and potentially more efficient approach to treating severe polyps is to target eosinophils directly using a monoclonal antibody. Previous reports have shown some benefit targeting IL-5 ligand itself with mepolizumab but the potential benefit of directly eliminating eosinophils by shutting down cellular signaling with benralizumab would be expected to have a more dramatic effect and needs to be investigated.
236 studies on the registry are indexed under Nasal Polyps; 68 are open to participants now.
This study's enrollment of 33 is below the median of 60 across 181 interventional studies indexed under Nasal Polyps.
Browse Nasal Polyps studies →Johns Hopkins University is the lead sponsor of 1,815 studies on the registry; 315 are open to participants now.
Of its 208 completed or terminated interventional studies of FDA-regulated products, 144 (69%) have results posted.
Compared within Nasal Polyps, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Disease. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Benralizumab Active treatment group delivered subcutaneously
Drug: Benralizumab
Placebo treatment group delivered subcutaneously
Drug: Placebo
30mg Benralizumab will be delivered subcutaneously
Also known as: Fasenra
Subcutaneous placebo injection
Change in Nasal Polyp Score
Change in endoscopic nasal polyp score after 6 months of treatment. Nasal Polyp Score (NPS): the change in mean score from Screen visit (Week 5) bilateral endoscopic nasal polyp score as compared to score at end of treatment (Week 25). Higher scores indicate increase in number of polyps and/or polyp size. The score is the sum of the right and left nostril scores, as evaluated by nasal endoscopy. NPS score key: 0 = No visible polyps; 1 = Small amount of polypoid disease confined within the middle meatus; 2 = Multiple polyps occupying the middle meatus; 3 = Polyps extending beyond the middle meatus; 4 = Polyps completely obstructing the nasal cavity. Reported data is a difference in the NPS between Week 25 and Week 5.
Time frame: Week 5 and Week 25
Change in Nasal Polyp Size as Assessed by the Lund Mackay Score
Computed Tomography (CT) scan of the sinus was performed at screening (Week 5) and then again at the end of treatment (Week 25). Sinus CT images were obtained to determine the Lund Mackay Score (LMS), a widely used method for radiologic staging of nasal polyposis. The mean change in the LMS was determined by comparing the scores from Week 5 to Week 25. Each sinus group is graded between 0 and 2 (0: no abnormality; 1: partial opacification; 2: total opacification). The ostiomeatal complex is scored as "0" not obstructed) or "2" (obstructed). Overall score range of 0-24. Higher scores indicate progression of nasal polyposis disease. Reported data is a difference in the LMS between Week 25 and Week 5.
Time frame: Week 5 and Week 25
Change in Symptom Severity Score as Assessed by the Sino-nasal Outcome Test
The Sino-nasal Outcome Test (SNOT-22) is a condition-specific health-related quality of life assessment that captures patient-reported physical problems, functional limitations, and emotional consequences of sinonasal conditions for the 2 weeks prior to completing the test. Participants completed the SNOT-22 at treatment Week 0 and at Treatment Week 20. Patients rated their symptom severity and symptom impact over the previous 2 weeks using a 6-point scale (0- No Problem to 5- Problem as bad as it can be). The total score is the sum of individual item scores and has a range from 0 to 110. Higher scores indicate more severe symptoms. Outcome measure data shows change in SNOT-22 scores between treatment Week 20 and Week 0.
Time frame: Treatment Week 0 and Week 20
Change in The University of Pennsylvania Smell Identification Test Score
The University of Pennsylvania Smell Identification Test (UPSIT) is a quantitative test of olfactory function that uses microencapsulated odorants that are released by scratching standardized odor-impregnated test booklets. Four booklets with 10 questions in each booklet on odor identification. Patients were asked to identify the odor by scratching the test area then selecting their answer using multiple-choice format that lists 4 different possible answers for each question. The mean change in the UPSIT was determined by comparing the score from Week 5 to the score in Week 25. The test is a forced-choice test meaning the patient is required to mark one of the four answers even if a smell is not perceived. Scores are based on number of correctly identified odors (score range 0 to 40). Higher scores indicate subject's ability to correctly identify odors. Reported data is a difference in the UPSIT score between Week 25 and Week 5.
Time frame: Week 5 and Week 25
Change in Absolute Eosinophil Count
Complete Blood Count (CBC) to determine change in absolute eosinophil count. Normal Range 30-300 cells/uL.
Time frame: Assessed at Treatment Week 0 and Week 20
Utilization of Prednisone as a Rescue Medication
Use of Prednisone as a rescue medication during the treatment phase (week 0 through week 20) was measured in total milligrams (mg) that were taken by participant.
Time frame: 20 weeks
Time to Surgery
Time frame: 24 weeks
Number of Participants Who Dropped Out
Number of participants who dropped out monitored continuously throughout the study up to 29 weeks.
Time frame: Up to 29 weeks
| Milestone | Benralizumab Treatment Group | Placebo Group |
|---|---|---|
| Started | 12 | 12 |
| Completed | 12 | 12 |
| Not completed | 0 | 0 |
Change in endoscopic nasal polyp score after 6 months of treatment. Nasal Polyp Score (NPS): the change in mean score from Screen visit (Week 5) bilateral endoscopic nasal polyp score as compared to score at end of treatment (Week 25). Higher scores indicate increase in number of polyps and/or polyp size. The score is the sum of the right and left nostril scores, as evaluated by nasal endoscopy. NPS score key: 0 = No visible polyps; 1 = Small amount of polypoid disease confined within the middle meatus; 2 = Multiple polyps occupying the middle meatus; 3 = Polyps extending beyond the middle meatus; 4 = Polyps completely obstructing the nasal cavity. Reported data is a difference in the NPS between Week 25 and Week 5.
| score on a scale | Benralizumab Treatment Group | Placebo Group |
|---|---|---|
| Change in Nasal Polyp Score | .9 (0 to 3) | .3 (-1 to 2) |
Computed Tomography (CT) scan of the sinus was performed at screening (Week 5) and then again at the end of treatment (Week 25). Sinus CT images were obtained to determine the Lund Mackay Score (LMS), a widely used method for radiologic staging of nasal polyposis. The mean change in the LMS was determined by comparing the scores from Week 5 to Week 25. Each sinus group is graded between 0 and 2 (0: no abnormality; 1: partial opacification; 2: total opacification). The ostiomeatal complex is scored as "0" not obstructed) or "2" (obstructed). Overall score range of 0-24. Higher scores indicate progression of nasal polyposis disease. Reported data is a difference in the LMS between Week 25 and Week 5.
| score on a scale | Benralizumab Treatment Group | Placebo Group |
|---|---|---|
| Change in Nasal Polyp Size as Assessed by the Lund Mackay Score | -4.2 ± 1.1 | -1.6 ± 1.2 |
The Sino-nasal Outcome Test (SNOT-22) is a condition-specific health-related quality of life assessment that captures patient-reported physical problems, functional limitations, and emotional consequences of sinonasal conditions for the 2 weeks prior to completing the test. Participants completed the SNOT-22 at treatment Week 0 and at Treatment Week 20. Patients rated their symptom severity and symptom impact over the previous 2 weeks using a 6-point scale (0- No Problem to 5- Problem as bad as it can be). The total score is the sum of individual item scores and has a range from 0 to 110. Higher scores indicate more severe symptoms. Outcome measure data shows change in SNOT-22 scores between treatment Week 20 and Week 0.
| score on a scale | Benralizumab Treatment Group | Placebo Group |
|---|---|---|
| Change in Symptom Severity Score as Assessed by the Sino-nasal Outcome Test | -19.2 ± 2.6 | -14.6 ± 20.1 |
The University of Pennsylvania Smell Identification Test (UPSIT) is a quantitative test of olfactory function that uses microencapsulated odorants that are released by scratching standardized odor-impregnated test booklets. Four booklets with 10 questions in each booklet on odor identification. Patients were asked to identify the odor by scratching the test area then selecting their answer using multiple-choice format that lists 4 different possible answers for each question. The mean change in the UPSIT was determined by comparing the score from Week 5 to the score in Week 25. The test is a forced-choice test meaning the patient is required to mark one of the four answers even if a smell is not perceived. Scores are based on number of correctly identified odors (score range 0 to 40). Higher scores indicate subject's ability to correctly identify odors. Reported data is a difference in the UPSIT score between Week 25 and Week 5.
| score on a scale | Benralizumab Treatment Group | Placebo Group |
|---|---|---|
| Change in The University of Pennsylvania Smell Identification Test Score | 6.6 ± 2.2 | 4.3 ± 2.5 |
Complete Blood Count (CBC) to determine change in absolute eosinophil count. Normal Range 30-300 cells/uL.
| cells/uL | Benralizumab Treatment Group | Placebo Group |
|---|---|---|
| Change in Absolute Eosinophil Count | 678 ± 119 | 196.7 ± 171 |
Use of Prednisone as a rescue medication during the treatment phase (week 0 through week 20) was measured in total milligrams (mg) that were taken by participant.
| mg | Benralizumab Treatment Group | Placebo Group |
|---|---|---|
| Utilization of Prednisone as a Rescue Medication | 302.5 ± 407.77 | 297.5 ± 294.12 |
No measurements were reported for this outcome.
Number of participants who dropped out monitored continuously throughout the study up to 29 weeks.
| Participants | Benralizumab Treatment Group | Placebo Group |
|---|---|---|
| Number of Participants Who Dropped Out | 0 | 0 |
Collected over Approximately 9 months (from date of signed consent to 30 days after completion of therapy).. Non-serious events are listed at a 1% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Benralizumab Treatment Group | 0/12 (0%) | 0/12 (0%) | 1/12 (8.3%) |
| Placebo Group | 0/12 (0%) | 0/12 (0%) | 2/12 (16.7%) |
| Event | Benralizumab Treatment Group | Placebo Group |
|---|---|---|
| Upper Respiratory Infection (URI)General disorders | 1/12 | 2/12 |
| Age, Categorical(Participants) | Benralizumab Treatment Group | Placebo Group | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 11 | 11 | 22 |
| >=65 years | 1 | 1 | 2 |
| Age, Continuous(years) | Benralizumab Treatment Group | Placebo Group | Total |
|---|---|---|---|
| Mean | 49.8 (33 to 70) | 50.8 (35 to 67) | 50.3 (33 to 70) |
| Sex: Female, Male(Participants) | Benralizumab Treatment Group | Placebo Group | Total |
|---|---|---|---|
| Female | 5 | 5 | 10 |
| Male | 7 | 7 | 14 |
| Ethnicity (NIH/OMB)(Participants) | Benralizumab Treatment Group | Placebo Group | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 12 | 12 | 24 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Benralizumab Treatment Group | Placebo Group | Total |
|---|---|---|---|
| United States | 12 | 12 | 24 |
PDFs hosted by the registry, ClinicalTrials.gov.
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Studies of the drug tested here: Benralizumab