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Efficacy and Safety Study of Benralizumab for Patients With Severe Nasal Polyposis (OSTRO)

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ClinicalTrials.gov Identifier: NCT03401229
Recruitment Status : Recruiting
First Posted : January 17, 2018
Last Update Posted : April 24, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
The aim of this present study is to investigate the use of benralizumab as treatment for severe nasal polyposis. The effect of benralizumab on nasal polyps will be assessed over a 56 weeks of treatment period in patients with severe bilateral nasal polyposis who are still symptomatic despite standard of care therapy, i.e current use of intranasal corticosteroids (INCS) and prior surgery and/or use of systemic corticosteroids. The first 200 patients that complete the 56-week treatment will have a 6 month follow-up (FU) period without dosing.

Condition or disease Intervention/treatment Phase
Nasal Polyposis Biological: Benralizumab 30 mg SC + Mometasone Furoate Biological: Matching placebo SC + Mometasone Furoate Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study Of Benralizumab in Patients With Severe Nasal Polyposis
Actual Study Start Date : January 15, 2018
Estimated Primary Completion Date : September 4, 2020
Estimated Study Completion Date : September 4, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Benralizumab 30mg SC + MF
SC - subcutaneously MF - Mometasone Furoate
Biological: Benralizumab 30 mg SC + Mometasone Furoate

Benralizumab injection is 30mg/ml SC clear to opalescent, colourless to yellow solution in accessorized pre-filled syringe.

Benralizumab 30 mg SC will be injected every 4 weeks for the first 3 doses - Weeks 0 , 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48. Total of 8 doses.

Mometasone Furoate Nasal Spray (MFNS) - intranasal corticosteroid - 2 doses (1 dose = 50 micrograms/actuation) in each nostril twice daily. Total daily dose of 400mcg. MFNS will be used for a minimum of 4 weeks prior to randomization and will be continued throughout the study.


Placebo Comparator: Placebo SC + MF Biological: Matching placebo SC + Mometasone Furoate

Matching placebo injection is SC clear to opalescent, colourless to yellow solution in accessorized pre-filled syringe.

Matching placebo SC will be injected every 4 weeks for the first 3 doses - Weeks 0 , 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48. Total of 8 doses.

Mometasone Furoate Nasal Spray (MFNS) - intranasal corticosteroid - 2 doses (1 dose = 50 micrograms/actuation) in each nostril twice daily. Total daily dose of 400mcg. MFNS will be used for a minimum of 4 weeks prior to randomization and will be continued throughout the study.





Primary Outcome Measures :
  1. Effect of benralizumab on nasal polyp burden [ Time Frame: Week 56 (visit 11) ]
    Change from baseline in endoscopic total nasal polyp score (NPS). NPS (maximum 8) is the sum of the right and left nostril scores

  2. Effect of benralizumab on patient reported nasal blockage (NB) [ Time Frame: Week 56 (visit 11) ]
    Change from baseline in mean nasal blockage score (NBS). NBS is assessed in daily diary by asking patients to rate the severity of their worst nasal blockage over the past 24 hours using the following response options: 0 - None; 1 - Mild; 2 - Moderate; 3 - Severe


Secondary Outcome Measures :
  1. Effect of benralizumab on disease specific health-related quality of life (HRQoL) [ Time Frame: Week 56 (visit 11) ]
    Change from baseline in SinoNasal Outcome Test (SNOT-22) score. SNOT-22 captures patient-reported physical problems, functional limitations, and emotional consequences of sinonasal condition. It`s patient-reported symptom severity and symptom impact over the past 2 weeks and are captured via a 6-point scale (0- No Problem to 5- Problem as bad as it can be). The total score is the sum of item scores and has a range from 0 to 110

  2. Effect of benralizumab on nasal polyp (NP) surgery [ Time Frame: by Week 56 (visit 11) ]
    Time to first NP surgery

  3. Proportion of NP Surgery [ Time Frame: by Week 56 (visit 11) ]
    Proportion of patients with surgery for NP

  4. Systemic corticosteroids (SCS) use for relief of nasal symptoms [ Time Frame: by Week 56 (visit 11) ]
    Proportion of patients with SCS use for NP

  5. Systemic corticosteroids (SCS) use for relief of nasal symptoms [ Time Frame: by Week 56 (visit 11) ]
    Time to first SCS course for NP

  6. Symptoms associated with nasal polyps [ Time Frame: Week 56 (visit 11) ]
    Change from baseline in nasal symptom score(s) as captured in the daily diary. Patients report the severity of symptom related to NP at its worst using a 4-point verbal rating scale (0-None to 3-Severe).

  7. Symptoms associated with nasal polyps [ Time Frame: Week 56 (visit 11) ]

    Sense of smell captured as change from baseline in University of Pennsylvania Smell Identification Test (UPSIT) score.

    It is a quantitative test of olfactory function which uses microencapsulated odorants that are released by scratching standardized odor-impregnated test booklets. Four booklets each with 10 odorants each are used for the test. Patients are asked to identify the odor using multiple choice format which lists different possibilities. Scores are based on number of correctly identified odors (score range 0 to 40).


  8. Sinus opacification by computed tomography (CT) scan (subset of patients) [ Time Frame: Week 56 (visit 11) ]
    Change from baseline in Lund Mackay score

  9. Patient-reported general health status [ Time Frame: Week 56 (visit 11) ]
    Change from baseline in Short Form 36-item Health survey, Version 2 (SF-36v2)

  10. Systemic corticosteroids (SCS) use for relief of nasal symptoms [ Time Frame: by Week 56 (visit 11) ]
    Total SCS dose used

  11. Systemic corticosteroids (SCS) use for relief of nasal symptoms [ Time Frame: by Week 56 (visit 11) ]
    Number of courses of SCS for NP

  12. Systemic corticosteroids (SCS) use for relief of nasal symptoms [ Time Frame: by Week 56 (visit 11) ]
    Total duration of SCS use for NP

  13. Sinus opacification by computed tomography (CT) scan (subset of patients) [ Time Frame: Week 56 (visit 11) ]
    Change from baseline in sinus severity score by Quantitative CT analysis


Other Outcome Measures:
  1. Assessment of the safety of benralizumab [ Time Frame: by Week 56 (visit 11) ]
    Numbers of adverse events (AEs) and serious adverse events (SAEs)

  2. Assessment of the immunogenicity of benralizumab [ Time Frame: Week 56 (visit 11) ]
    Presence and absence of benralizumab anti-drug antibodies (ADA)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions, listed in the informed consent form (ICF) and in protocol.
  2. Provision of signed and dated, written informed consent form (ICF) prior to any mandatory study specific procedures, sampling, and analyses and according to international guidelines and/or applicable European Union (EU) guidelines.
  3. Provision of signed and dated written genetic informed consent in patients that agree to participate in the genetic sampling, prior to collection of sample for genetic analysis.
  4. Female or male patients aged 18 to 75 years inclusive, at the time of signing the ICF.
  5. Patients with bilateral sinonasal polyposis that, despite treatment with a stable dose of intranasal corticosteroids (INCS) for at least 4 weeks prior to V1, in addition to history of treatment with systemic (SCS -oral, parenteral) or prior surgery for nasal polyposis (NP), have severity consistent with a need for surgery as described by:

    • A minimum total Nasal Polyp Score (NPS) of 5 out of a maximum score of 8 (with a unilateral score of at least 2 for each nostril) at V1, and continuously maintained at V2 to meet the randomization criterion, as determined by the study Imaging Core Lab;
    • Ongoing symptoms for at least 12 weeks prior to V1;
    • Patient-reported moderate to severe nasal blockage score (NBS) 2 or 3 over the 2-weeks prior to V1 (2-week recall assessment of symptoms, scores 0-none to 3-severe).
  6. SNOT-22 total score ≥ 30 at enrolment.

    Patient must meet the following criteria (points 7-10) at the randomization visit:

  7. At least 8 days of evaluable daily diary data in the 14-day period prior to randomization (baseline bi-weekly mean score collected from study Day -13 to study Day 0).
  8. At randomization, a bi-weekly mean NBS ≥ 1.5.
  9. SNOT-22 total score ≥ 30 at randomization.
  10. At least 70% compliance with INCS during the run-in period based on daily diary.
  11. Patients with a minimum weight of 40kg.
  12. Negative serum pregnancy test result and a negative urine pregnancy test at randomization for female patients of childbearing potential.
  13. Women of childbearing potential (WOCBP) must use an effective form of birth control as defined in the Clinical Study Protocol (CSP).

15. Male subjects who are sexually active must be surgically sterile at least one year prior to Visit 1 or must use an adequate method of contraception (condom or condom with spermicide depending on local regulations) from the first dose of IP until 16 weeks after their last dose. Men with a partner or partners who is (are) not of childbearing potential are exempt of these requirements

Exclusion Criteria:

  1. Patients who have undergone any nasal and/or sinus surgery within 3 months prior to V1.
  2. Patients with conditions or concomitant disease that makes them non evaluable for the co-primary efficacy endpoint such as:

    • Unilateral antrochoanal polyps;
    • Nasal septal deviation that occludes at least one nostril;
    • Acute sinusitis, nasal infection, or upper respiratory infection at screening or in the 2 weeks before screening;
    • Current rhinitis medicamentosa;
    • Allergic fungal rhinosinusitis (AFRS) or Allergic fungal sinusitis (AFS);
    • Nasal cavity tumors.
  3. Clinically important comorbidities that could confound interpretation of clinical efficacy results including, but not limited to: active upper or lower respiratory tract infection, cystic fibrosis, primary ciliary dyskinesia, eosinophilic diseases other than asthma (e.g. allergic bronchopulmonary aspergillosis/mycosis, eosinophilic granulomatosis with polyangitis [Churg-Strauss syndrome], hypereosinophilic syndromes), granulomatosis with polyangitis (Wegener's granulomatosis), Young's syndrome, etc.
  4. Any disorder, including but not limited to: cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator or AstraZeneca and could:

    • Affect the safety of the patient throughout the study;
    • Influence the findings of the studies or their interpretations;
    • Impede the patient's ability to complete the entire duration of study.
  5. Patients experiencing an asthma exacerbation requiring systemic (oral and/or parenteral) corticosteroids treatment or hospitalization (>24hrs) for treatment of asthma within 4 weeks prior to V1.
  6. History of anaphylaxis to any biologic therapy or vaccine.
  7. Known history of allergy or reaction to any component of the Investigational Product (IP) formulation.
  8. History of Guillain-Barré syndrome.
  9. A helminth parasitic infection diagnosed within 24 weeks prior to V1 and has not been treated with, or has failed to respond to standard of care therapy.
  10. Current malignancy, or history of malignancy, except for: - Patients who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that patient is in remission and curative therapy was completed at least 12 months prior to V1; - Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to V1.

    NOTE: Hormonal therapy is allowed. As long as the cancer is in remission for 5 years, the patient is eligible.

  11. Any clinically significant cardiac disease or any electrocardiogram (ECG) abnormality obtained during the screening/run-in period, which may put the patient at risk or interfere with study assessments.
  12. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology (confirmed by additional testing, e.g. hepatitis C RNA test, if indicated), or a positive medical history for hepatitis B or C (Note: Patients with history of hepatitis B vaccination without history of hepatitis B are allowed to enroll).
  13. History of known immunodeficiency disorder, including a positive human immunodeficiency virus (HIV) test.
  14. Infection requiring systemic antibiotics (Ab) within 14 days prior to V1
  15. Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, or any experimental anti-inflammatory therapy) within 3 months prior to V1.
  16. Receipt of any marketed or investigational biologic products (monoclonal or polyclonal antibody) within 6 months or 5 half-lives prior to the date informed consent, is obtained, whichever is longer, prior to V1 and during the study period. This also applies to patients who previously participated in clinical studies and were treated with monoclonal antibodies (e.g. mepolizumab, reslizumab, dupilumab, omalizumab). Note that this restriction do not apply to patients, who are confirmed to have only received treatment with placebo.
  17. Previous receipt of benralizumab.
  18. Receipt of immunoglobulin or blood products within 30 days prior to V1.
  19. Receipt of live attenuated vaccines 30 days prior to the date of randomization.
  20. Receipt of any investigational drug within 30 days or 5 half-lives whichever is longer prior to randomization.
  21. Receipt of systemic corticosteroid 4 weeks prior to V1, or a scheduled systemic corticosteroid treatment during the study period.

    NOTE: Sustained release steroids (e.g. Kenalog [Triamcinolone acetonide]) or depot injections require minimum 6 weeks washout prior to V1.

  22. Receipt of leukotriene antagonist/modifiers for patients who were not on a continuous stable dose for ≥30 days prior to V1.
  23. Concurrent enrolment in another clinical drug interventional trial.
  24. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥ 3 times the upper limit of normal (ULN) confirmed during screening period.
  25. Previous randomization in the present study.
  26. Planned major surgical procedures or scheduled NP surgery at the time of the study enrolment and randomization.
  27. Initiated or is being maintained on an aspirin desensitization regimen for the management of aspirin exacerbated respiratory disease (AERD) at the time of study enrolment or during the run-in period.
  28. For women only - currently pregnant (or intend to become pregnant), breastfeeding or lactating.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03401229


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

  Show 126 Study Locations
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Claus Bachert, Prof. dr. h.c. University Hospital Ghent, de Pintelaan 185, 9000 Ghent, Belgium

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03401229     History of Changes
Obsolete Identifiers: NCT03627286
Other Study ID Numbers: D3252C00001
2017-003675-61 ( EudraCT Number )
First Posted: January 17, 2018    Key Record Dates
Last Update Posted: April 24, 2019
Last Verified: April 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
Polyps
Nasal polyps
Nasal polyposis
Nose diseases
Respiratory tract diseases
Otorhinolaryngologic diseases
Benralizumab
Mometasone furoate

Additional relevant MeSH terms:
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Benralizumab
Colorectal Neoplasms
Nasopharyngeal Neoplasms
Nasal Polyps
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Nose Diseases
Respiratory Tract Diseases
Polyps
Pathological Conditions, Anatomical
Mometasone Furoate
Anti-Inflammatory Agents
Dermatologic Agents
Anti-Allergic Agents
Anti-Asthmatic Agents