Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

NAsal Polyps: Inflammatory & Molecular Phenotyping of Responders to Benralizumab (NAPPREB)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04185012
Recruitment Status : Recruiting
First Posted : December 4, 2019
Last Update Posted : November 18, 2021
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Humanitas Clinical and Research Center

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

Background and rationale:

Phase III-b study.

Population and patient selection criteria: Adult patients with Chronic Rhinosinusitis with Nasal Polyps (allergic and non-allergic) requiring at least 1000 mg oral prednisone over the previous twelve months to control symptoms of rhinosinusitis, and with:

  • Nasal polyps score (Meltzer et al.) ≥ 5
  • Symptoms VAS scores (for nasal obstruction, hyposmia, post-nasal drip, sneezing, rhinorrea; 0-10 for each symptom) > 24 Sample size: 20 subjects.

Study design and study duration:

This is a pilot, prospective, double-blind placebo-controlled (DBPC) phase III-b trial with Benralizumab 30 mg administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks, for a treatment-period of 16 weeks (followed up at 32 and 52 weeks) in patients with chronic rhinosinusinusitis with nasal polyps (CRSwNP).

Description of study treatment/product/intervention: Benralizumab, 30 mg subcutaneously every 4 week for the first 3 doses, and then every 8 weeks.

Objectives:

  • Primary objective: To assess the clinical efficacy of Benralizumab on CRSwNP at week 24 (vs baseline) after the beginning of treatment, and to correlate the presence of baseline biomarkers with nasal polyp (NP) score improvement, in order to identify any possible predictive biomarker of response to Benralizumab.
  • Secondary objective: In the follow up phase we will monitor all the biomarkers at 32 and 52 weeks , this monitoring will ascertain if any of those will predict relapse of nasal polyps and consequently when Benralizumab treatment has to be reinstalled.
  • Safety objective: To evaluate the safety and tolerability of Benralizumab in patients with CRSwNP

Statistical methods, data analysis: Descriptive analysis of all collected variables at all time-points will be performed. Patients will be classified into "responders" and "non responders", for primary endopoint variable. Continuous variables will be evaluated with the normality test of Kolmogorov-Smirnov and compared with ANOVA or the Mann-Whitney test, depending on the normality of distribution. Categorical variables will be compared using Fisher's exact test.

Ethical considerations: The study will be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with ICH/Good Clinical Practice, applicable regulatory requirements and the Sponsor policy on Bioethics and Human Biological Samples.


Condition or disease Intervention/treatment Phase
Nasal Polyps Biological: Benralizumab Biological: Placebo Phase 3

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind, placebo-controlled clinical trial. Patients will be divided in two arms with 1:1 randomization to Treatment or Placebo.
Masking: Single (Investigator)
Masking Description:

Randomization will occur by assigning a unique sequential study code to a balanced number of randomly assorted treatment vials.

An online open source randomization software will be used to assign treatment groups, and this will be done by an external person from those who will follow and treat the patients.

Patients randomization will be blinded to the patients themselves and to all the personnel that will have contact with them during the trial
Primary Purpose: Treatment
Official Title: NAsal Polyps: Inflammatory & Molecular Phenotyping of Responders to Benralizumab
Actual Study Start Date : February 24, 2020
Estimated Primary Completion Date : March 28, 2022
Estimated Study Completion Date : July 30, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Benralizumab
Benralizumab 30 mg administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks, for a treatment-period of 16 weeks
 Biological: Benralizumab
Benralizumab 30 mg administered subcutaneously Q4W for the first 3 doses and then Q8W, for a 16 weeks treatment-period
Placebo Comparator: Placebo
Placebo administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks, for a treatment-period of 16 weeks
 Biological: Placebo
Placebo administered subcutaneously Q4W for the first 3 doses and then Q8W, for a 16 weeks treatment-period


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Significant reduction of the Nasal polyps Score (range: 0-8; higher values mean larger nasal polyps size) [ Time Frame: at week 24 (vs baseline) ]
    score reduction of 1.5


Secondary Outcome Measures :
  1. Reduction in Lund-MacKay Score (range: 0-24; higher values mean larger nasal polyps extension) [ Time Frame: at week 24 (vs baseline) ]
    >50% of baseline

  2. Improvement of Sino-Nasal Outcome Test (SNOT-22; range: 0-110; higher values mean poorer disease-related quality of life) [ Time Frame: at week 24 (vs baseline) ]
    >40% of baseline

  3. Improvement of smell Visual Analogue Scale (VAS; range: 0-10; higher values mean worse smell) [ Time Frame: at week 24 (vs baseline) ]
    >50% of baseline


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Adult patients with Chronic Rhinosinusitis with Nasal Polyps (allergic and non-allergic) requiring at least 1000 mg oral prednisone over the previous twelve months to control symptoms of rhinosinusitis, and with:

  • Nasal polyps score (Meltzer et al.) > 5
  • Symptoms VAS scores (for nasal obstruction, hyposmia, post-nasal drip, sneezing, rhinorrea; 0-10 for each symptom) > 24
  • Provision of informed consent prior to any study specific procedure

Exclusion Criteria:

  • Patients < 18 years age
  • Pregnant women
  • Biologic therapy in the past 6 months (or at least a period corresponding to 5 half-life of used drugs) (eg: omalizumab, mepolizumab, reslizumab, dupilumab)
  • Previous treatment with Benralizumab
  • Known hypersensitivity to benralizumab or any of its excipients
  • Immunosuppression other than oral steroids in the past 3 months
  • Allergen immunotherapy in the past 6 months
  • Serious life threatening cardiopulmonary disorders
  • Systemic immunologic disorder in the last 12 months
  • Positive history for malignant tumors ever in patient's life

  • Patients with conditions or concomitant diseases making them non evaluable at visit 1 or for the primary efficacy endpoint:

    1. Ongoing rhinitis medicamentosa
    2. Nasal septal deviation occluding at least one nostril
    3. Acute sinusitis, nasal infection, upper respiratory infections
    4. Radiologic suspicion or confirmed invasive or expansive fungal rhinosinusitis
    5. Eosinophilic Granulomatosis with Polyangiitis (previously named Churg-Strauss Syndrome)
    6. Granulomatosis with Polyangiitis (previously named Wegener's granulomatosis)
    7. Young's Syndrome
    8. Kartagener's Syndrome
    9. all ciliary dyskinesia
    10. Cystic Fibrosis
  • Systemic corticosteroid treatment for other chronic conditions (i.e.: autoimmune disorders, tumors,….)
  • Evidence of active systemic immunedepression (i.e..: primary or secondary immunodeficiency)
  • Patients with severe asthma, defined according to ERS/ATS definition
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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): NCT04185012


Contacts
Layout table for location contacts
Contact: Giorgio Walter Canonica, MD +390288247013 giorgio_walter.canonica@hunimed.eu
Contact: Enrico Heffler, MD, PhD +390288247013 enrico.heffler@hunimed.eu

Locations
Layout table for location information
Italy
Humanitas Clinical and Research Hospital Recruiting
Rozzano, MI, Italy, 20089
Contact: Giorgio Walter Canonica, MD    +390288247013    giorgio_walter.canonica@hunimed.eu   
Contact: Enrico Heffler, MD, PhD    +390288247013    enrico.heffler@hunimed.eu   
Sponsors and Collaborators
Humanitas Clinical and Research Center
AstraZeneca
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Humanitas Clinical and Research Center
ClinicalTrials.gov Identifier: NCT04185012    
Other Study ID Numbers: NAPPREB
First Posted: December 4, 2019    Key Record Dates
Last Update Posted: November 18, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Humanitas Clinical and Research Center:
Benralizumab
Biomarkers
Eosinophils
Additional relevant MeSH terms:
Layout table for MeSH terms
Nasal Polyps
Polyps
Pathological Conditions, Anatomical
Nose Diseases
Respiratory Tract Diseases
 Otorhinolaryngologic Diseases
Benralizumab
Anti-Asthmatic Agents
Respiratory System Agents