Benralizumab Effect on Severe Chronic Rhinosinusitis With Eosinophilic Polyposis

NCT03450083 | Completed Phase 2 Results FDA Drug

• 1 other identifier: IRB00112910
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Benralizumab will be used in a placebo controlled randomized study to treat severe chronic rhinosinusitis with nasal polyps

Conditions

Chronic Rhinosinusitis (Diagnosis); Nasal Polyps; Eosinophilia

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 5 and Week 25

Secondary Outcomes (7)

• Change in Nasal Polyp Size as Assessed by the Lund Mackay Score

  Week 5 and Week 25

• Change in Symptom Severity Score as Assessed by the Sino-nasal Outcome Test

  Treatment Week 0 and Week 20

• Change in The University of Pennsylvania Smell Identification Test Score

  Week 5 and Week 25

• Change in Absolute Eosinophil Count

  Assessed at Treatment Week 0 and Week 20

• Utilization of Prednisone as a Rescue Medication

  20 weeks

Study Arms (2)

Benralizumab treatment group

ACTIVE COMPARATOR

Benralizumab Active treatment group delivered subcutaneously

Drug: Benralizumab

Placebo group

PLACEBO COMPARATOR

Placebo treatment group delivered subcutaneously

Drug: Placebo

Interventions

Benralizumab DRUG

30mg Benralizumab will be delivered subcutaneously

Also known as: Fasenra

Benralizumab treatment group

Placebo DRUG

Subcutaneous placebo injection

Placebo group

Eligibility Criteria

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

You may qualify if:

• Adults aged 18-75
• Severe bilateral nasal polyps with average endoscopic score of at least 5
• Blood eosinophil count of at least 300/ul at screening
• At least 1000mg prednisone (or equivalent) over the previous 12 months to control symptoms
• At least one prior nasal surgical polypectomy
• Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
• Female subjects: Women of childbearing potential (WOCBP) must use an effective form of birth control (confirmed by the Investigator). Effective forms of birth control include: true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective Intra-uterine device (IUD) intrauterine device/ levonogestrel Intrauterine system (IUS), Depo-Provera(tm) injections, oral contraceptive, and Evra Patch(tm) or Nuvaring(tm). WOCBP must agree to use effective method of birth control, as defined above, from enrolment, throughout the study duration and within 16 weeks after last dose of IP, and have negative serum pregnancy test result on Visit 0.
• Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for 12 months prior to the planned date of visit -1 without an alternative medical cause. The following age-specific requirements apply:
• Women \<50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range.
• Women ≥50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.
• All male subjects who are sexually active must agree to use an acceptable method of contraception (condom with or without spermicide, vasectomy) from Visit 0 until 16 weeks after their last dose.

You may not qualify if:

• Immunosuppression other than oral steroids in the past 3 months
• Allergen immunotherapy build up phase in the past 3 months
• Symptomatic or untreated life threatening cardiopulmonary disorders
• Subjects who are febrile (≥38°C; ≥100.4°F);
• History of cancer: Subjects who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the subject is in remission and curative therapy was completed at least 12 months prior to the date informed consent, and assent when applicable was obtained. Subjects who have had other malignancies are eligible provided that the subject is in remission and curative therapy was completed at least 5 years prior to the date informed consent, and assent when applicable, was obtained.
• A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy.
• Pregnant or nursing
• If female and of child-bearing potential, positive pregnancy test or failure to adhere to acceptable method of contraception (with \<1% failure rate) during the study and for four months after the study.
• Receipt of any investigational non biologic within 30 days or 5 half-lives prior to visit 0, whichever is longer.
• A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
• Any other medical illness that precludes study involvement
• Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to be enrolled.
• Patients who are currently receiving or have previously received benralizumab or any other type of anti-interleukin therapy (i.e. mepolizumab, reslizumab, lebrikizumab etc.) within the last 4 months or 5 half-lives whichever is longer.
• History of anaphylaxis to any biologic therapy or vaccine.
• Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21224, United States

Location

Related Publications (2)

• 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

• Tversky J, Lane AP, Azar A. Benralizumab effect on severe chronic rhinosinusitis with nasal polyps (CRSwNP): A randomized double-blind placebo-controlled trial. Clin Exp Allergy. 2021 Jun;51(6):836-844. doi: 10.1111/cea.13852. Epub 2021 Feb 27.

  PMID: 33595845 DERIVED

MeSH Terms

Conditions

Disease; Nasal Polyps; Eosinophilia

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nose Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Polyps; Pathological Conditions, Anatomical; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Jody Tversky, MD
• Organization: Johns Hopkins University School of Medicine

hoddin1@jhmi.edu

410-550-8017

Study Officials

• Jody Tversky, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: March 1, 2018
• Study Start: July 1, 2017
• Primary Completion: January 1, 2020
• Study Completion: February 1, 2020
• Last Updated: February 11, 2021
• Results First Posted: January 22, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)