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

NCT03401229 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: D3252C000012017-003675-61
• Study Type: interventional
• Target: 413
• Locations: 8 countries
• Sites: 99

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.

Conditions

Nasal Polyposis

Keywords

Polyps; Nasal polyps; Nasal polyposis; Nose diseases; Respiratory tract diseases; Otorhinolaryngologic diseases; Benralizumab; Mometasone furoate

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Total NPS at Week 40

  Change from baseline in total nasal polyps score (NPS) at week 40 was defined as the endpoint value at week 40 minus the baseline value. The total NPS was the sum of the right and left nostril scores and maximum total NPS is 8, as evaluated by nasal endoscopy and the left and right score were based on central read with scale from 0 to 4 where higher score reflects heavier bilateral nasal polyp burden. Baseline was the last valid value on or prior to the date of randomization. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS\_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS\_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS\_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.

  Baseline to week 40

• Change From Baseline in NBS at Week 40

  Change from baseline in nasal blockage score (NBS) at week 40 was defined as the endpoint value at week 40 minus the baseline value. The NBS was captured by an item in NPSD. Patients were asked 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. The NBS and the changes from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS\_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS\_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS\_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.

  Baseline to week 40

Secondary Outcomes (33)

• Change From Baseline in SNOT-22 at Week 40

  Baseline to week 40

• Time to First NP Surgery and/or SCS Use for NP to Week 56

  Baseline to week 56

• Time to the First NP Surgery up to Week 56

  Baseline to week 56

• Change From Baseline in DSS at Week 40

  Baseline to week 40

• Change From Baseline in NPS at Week 56

  Baseline to week 56

Study Arms (2)

Benralizumab 30mg SC + MF

EXPERIMENTAL

SC - subcutaneously MF - Mometasone Furoate

Biological: Benralizumab 30 mg SC + Mometasone Furoate

Placebo SC + MF

PLACEBO COMPARATOR

Biological: Matching placebo SC + Mometasone Furoate

Interventions

Benralizumab 30 mg SC + Mometasone Furoate BIOLOGICAL

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.

Benralizumab 30mg SC + MF

Matching placebo SC + Mometasone Furoate BIOLOGICAL

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.

Placebo SC + MF

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions, listed in the informed consent form (ICF) and in protocol.
• 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.
• 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.
• Female or male patients aged 18 to 75 years inclusive, at the time of signing the ICF.
• 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).
• SNOT-22 total score ≥ 30 at enrolment.
• Patient must meet the following criteria (points 7-10) at the randomization visit:
• 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).
• At randomization, a bi-weekly mean NBS ≥ 1.5.
• SNOT-22 total score ≥ 30 at randomization.
• At least 70% compliance with INCS during the run-in period based on daily diary.
• Patients with a minimum weight of 40kg.

You may not qualify if:

• Patients who have undergone any nasal and/or sinus surgery within 3 months prior to V1.
• 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.
• 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.
• 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.
• 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.
• History of anaphylaxis to any biologic therapy or vaccine.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (99)

Research Site

Birmingham, Alabama, 35209, United States

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Fresno, California, 93720, United States

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Huntington Beach, California, 92647, United States

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La Mesa, California, 91942, United States

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Los Angeles, California, 90048, United States

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Los Angeles, California, 90095-1624, United States

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Orange, California, 92868, United States

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Roseville, California, 95661, United States

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Walnut Creek, California, 94598, United States

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Centennial, Colorado, 80112, United States

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Glenwood Springs, Colorado, 81601, United States

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Washington D.C., District of Columbia, 20037, United States

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Lake Mary, Florida, 32746, United States

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Atlanta, Georgia, 30308, United States

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Decatur, Georgia, 30030, United States

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Chicago, Illinois, 60611, United States

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Chicago, Illinois, 60657, United States

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Des Moines, Iowa, 50312, United States

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Kansas City, Kansas, 66160, United States

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Louisville, Kentucky, 40220, United States

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Baltimore, Maryland, 21224, United States

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Boston, Massachusetts, 02111, United States

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Boston, Massachusetts, 02114, United States

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Rochester, Minnesota, 55905, United States

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Lincoln, Nebraska, 68510, United States

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Hewlett, New York, 11557, United States

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New Windsor, New York, 12553, United States

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New York, New York, 10001, United States

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New York, New York, 10011, United States

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New York, New York, 10016, United States

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New York, New York, 10022, United States

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New York, New York, 10075, United States

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New York, New York, 10128, United States

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Plainview, New York, 11803, United States

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The Bronx, New York, 10461, United States

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White Plains, New York, 10605, United States

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Charlotte, North Carolina, 28210, United States

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Winston-Salem, North Carolina, 27103, United States

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Oklahoma City, Oklahoma, 73120, United States

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Philadelphia, Pennsylvania, 19107, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Charleston, South Carolina, 29425, United States

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Conroe, Texas, 77304, United States

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Houston, Texas, 77030, United States

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North Logan, Utah, 84341, United States

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Norfolk, Virginia, 23507, United States

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Richmond, Virginia, 23235, United States

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Spokane, Washington, 99201, United States

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Graz, 8036, Austria

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Linz, 4010, Austria

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Salzburg, 5020, Austria

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Sankt Pölten, 3100, Austria

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Vienna, 1090, Austria

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Vancouver, British Columbia, V5Z 1M9, Canada

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Hamilton, Ontario, L8S 1G5, Canada

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London, Ontario, N6A 4V2, Canada

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Mississauga, Ontario, L5A 3V4, Canada

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Ottawa, Ontario, K1G 6C6, Canada

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Montreal, Quebec, H2X 3E4, Canada

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Montreal, Quebec, H3G 1L5, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Québec, Quebec, G1V 4G5, Canada

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Québec, Quebec, G1V 4W2, Canada

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Trois-Rivières, Quebec, G8T 7A1, Canada

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Aalborg, 9000, Denmark

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Aarhus N, 8200, Denmark

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Hillerød, 3400, Denmark

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Hvidovre, 2650, Denmark

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København NV, 2400, Denmark

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Køge, 4600, Denmark

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Næstved, 4700, Denmark

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Odense C, 5000, Denmark

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Vejle, 7100, Denmark

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Aschaffenburg, 63739, Germany

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Berlin, 13353, Germany

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Dreieich, 63303, Germany

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Dresden, 01307, Germany

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Düsseldorf, 40225, Germany

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Göttingen, 37073, Germany

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Heidelberg, 69120, Germany

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Lübeck, 23538, Germany

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Münster, 48149, Germany

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Wiesbaden, 65183, Germany

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Budapest, 1083, Hungary

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Budapest, 1106, Hungary

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Debrecen, 4032, Hungary

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Eger, 3300, Hungary

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Nyíregyháza, 4400, Hungary

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Pécs, 7621, Hungary

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Veszprém, 8200, Hungary

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Lodz, 90-153, Poland

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Nadarzyn, 05-830, Poland

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Strzelce Opolskie, 47-100, Poland

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Warsaw, 02-547, Poland

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Wroclaw, 50-220, Poland

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Wroclaw, 53-301, Poland

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Related Publications (2)

• Bachert C, Han JK, Desrosiers MY, Gevaert P, Heffler E, Hopkins C, Tversky JR, Barker P, Cohen D, Emson C, Martin UJ, Shih VH, Necander S, Kreindler JL, Jison M, Werkstrom V. Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: A randomized, placebo-controlled trial. J Allergy Clin Immunol. 2022 Apr;149(4):1309-1317.e12. doi: 10.1016/j.jaci.2021.08.030. Epub 2021 Sep 29.

  PMID: 34599979 DERIVED

• Geng B, Dilley M, Anterasian C. Biologic Therapies for Allergic Rhinitis and Nasal Polyposis. Curr Allergy Asthma Rep. 2021 Jun 10;21(6):36. doi: 10.1007/s11882-021-01013-y.

  PMID: 34110505 DERIVED

Related Links

• The redacted CSP.
• The redacted SAP.

MeSH Terms

Conditions

Nasal Polyps; Polyps; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Interventions

benralizumab; Mometasone Furoate

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

During COVID-19 pandemic, for ongoing patients, patient dosing, scheduled visits, and nasal endoscopies are inevitable impacted. Week 40 was made as the primary timepoint to mitigate the impact of COVID disruptions on the primary endpoint.

Results Point of Contact

• Title: Maria Jison, MD Global Clinical Head, FASENRA, Late-stage R&I
• Organization: AstraZeneca

Maria.Jison@astrazeneca.com

+13013980340

Study Officials

• Claus Bachert, Prof. dr. h.c.

  University Hospital Ghent, de Pintelaan 185, 9000 Ghent, Belgium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2017
• First Posted: January 17, 2018
• Study Start: January 15, 2018
• Primary Completion: July 31, 2020
• Study Completion: July 31, 2020
• Last Updated: October 12, 2021
• Results First Posted: October 12, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

DK (9); DE (10); BE (3); HU (7); US (48); AU (5); CA (11); PL (6)