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EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients

Phase 4
Completed
Conditions
Chronic Rhinosinusitis With Nasal Polyps
Asthma
Interventions
Registration Number
NCT04998604
Lead Sponsor
Sanofi
Brief Summary

Primary Objective

-To evaluate the efficacy of dupilumab compared to omalizumab in reducing the polyp size and improving sense of smell

Secondary Objectives

* To evaluate the efficacy of dupilumab in improving chronic rhinosinusitis with nasal polyps (CRSwNP) symptoms at Week 24 compared to omalizumab

* To evaluate the efficacy of dupilumab in improving CRSwNP total symptom score (TSS) at Week 24 compared to omalizumab

* To evaluate the effect of dupilumab on health related quality of life (HRQoL) at week 24 compared to omalizumab

* To evaluate the efficacy of dupilumab in improving nasal peak inspiratory flow at Week 24 compared to omalizumab

* To evaluate the effect of dupilumab on CRSwNP overall disease severity at Week 24 compared to omalizumab

* To evaluate the safety of dupilumab and omalizumab

Detailed Description

Study duration per participant will be 38 weeks. The study will comprise 3 periods: 28 days ± 3 days screening and run-in period; 24 weeks Randomized investigational medicinal product (IMP) intervention period; up to 12 weeks follow-up period.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
320
Inclusion Criteria
  • Participant must be at least 18 (or the legal age of consent in the jurisdiction in which the study is taking place) years of age inclusive, at the time of signing the informed consent.

  • Participants with bilateral sino-nasal polyposis, that despite prior treatment with Systemic corticosteroids (SCS) anytime within the past 2 years; and/or medical contraindication/intolerance to SCS; and/or prior surgery for NP have:

    • An endoscopic bilateral NPS of at least 5 out of a maximum score of 8 (with a minimum score of 2 in each nasal cavity) at visit 1; AND
    • Ongoing symptoms of Nasal congestion/blockade/obstruction and loss of smell for at least 8 weeks before screening (Visit 1), AND
    • Nasal congestion/blockade/obstruction and a weekly average severity greater than 1 in the 7 days before randomization (Visit 2) AND
    • loss of smell symptom severity score 2 or 3 at screening (Visit 1) and a weekly average severity of greater than 1 in the 7 days before randomization (Visit 2).
  • Participants with a physician diagnosis of asthma based on the Global Initiative for Asthma (GINA) 2020 treated with low, medium or high dose inhaled corticosteroids (ICS) and a second controller (ie, LABA), a third controller is allowed but not mandatory. The dose regimen should be stable for at least 1 month before Visit 1 (screening visit) and during the screening and run-in period.

  • Asthma Control Questionnaire 5-question version (ACQ-5) score ≥1.5 at Visits 1 or 2.

  • Treatment with intranasal mometasone ≥200 μg once daily (QD) (or equivalent of another INCS) for 1 month prior to Visit 1 and during the run-in period (for CRSwNP).

  • Eligibility as per omalizumab drug-dosing table (serum IgE level ≥30 to ≤1500 IU/mL and body weight ≥30 to ≤150 kg) and ability to be dosed per the dosing table.

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

  • Participants who have undergone any sinus intranasal surgery (including polypectomy) within 6 months before Visit 1.
  • Participants who have had a sino-nasal surgery changing the lateral wall structure of the nose, making impossible the evaluation of NPS.
  • Participants with conditions/concomitant diseases making them non evaluable at Visit 1 or for the primary efficacy endpoint such as: Antrochoanal polyps, Nasal septal deviation that would occlude at least one nostril, Acute sinusitis, nasal infection, or upper respiratory infection.
  • Severe asthma exacerbation requiring treatment with SCS in the last 4 weeks prior to Visit 1 and during screening.
  • Severe concomitant illness(es) that, in the Investigator's judgment, would adversely affect the participant's participation in the study
  • Diagnosed with, suspected of, or at high risk of endoparasitic infection, and/or use of antiparasitic drugs within 2 weeks before Visit 1 (screening visit) or during the screening and run-in period.
  • History of human immunodeficiency virus (HIV) infection or positive HIV 1/2 serology at Visit 1 (screening visit).
  • Known or suspected immunodeficiency, including history of invasive opportunistic infections
  • Active malignancy or history of malignancy within 5 years before Visit 1 (screening visit), except completely treated in situ carcinoma of the cervix and completely treated and resolved non metastatic squamous or basal cell carcinoma of the skin.
  • History of systemic hypersensitivity or anaphylaxis to dupilumab and omalizumab, including any excipient
  • Treatment with a live (attenuated) vaccine within 4 weeks before Visit 1 (screening visit).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DupilumabPlaceboDosing every 2 weeks (Q2W)
OmalizumabPlaceboDosing Q2W or every 4 weeks (Q4W)
DupilumabDupilumabDosing every 2 weeks (Q2W)
OmalizumabOmalizumabDosing Q2W or every 4 weeks (Q4W)
Primary Outcome Measures
NameTimeMethod
Change from baseline to Week 24 in Nasal Polyp Score (NPS)Baseline to Week 24

The total nasal polyps score (NPS) is the sum of the right and left nostrils, ranging from 0 (no polyps) to 8 (large polyps causing complete obstruction).

Change from baseline to Week 24 in University of Pennsylvania Smell Identification Test (UPSIT)Baseline to Week 24

The UPSIT score ranges from 0 to 40, with 40 being the best possible score.

Secondary Outcome Measures
NameTimeMethod
Change from baseline to Week 24 in the loss of smell score of the CRSwNP Nasal Symptom DiaryBaseline to Week 24

Loss of smell scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms').

Change from baseline to Week 24 in the nasal congestion (NC) score of the CRSwNP Nasal Symptom DiaryBaseline to week 24

NC scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms').

Change from baseline to Week 24 in Total Symptom Score (TSS) derived from the CRSwNP Nasal Symptom DiaryBaseline to Week 24

TSS ranges from 0 to 9. Higher scores on the TSS indicate greater symptom severity.

Change from baseline to Week 24 in 22-Item Sino-nasal Outcome Test (SNOT-22) andBaseline to Week 24

SNOT-22 is a patient-reported outcome (PRO) questionnaire. Score ranges from 0 to 110 with higher score indicating greater rhinosinusitis related health burden.

Change from baseline to Week 24 in SNOT-22 nasal domain scoreBaseline to Week 24

SNOT-22 is a patient-reported outcome (PRO) questionnaire. Nasal domain score ranges from 0-40 with high score representing higher disease burden.

Change from baseline to Week 24 in Nasal Peak Inspiratory Flow (NPIF)Baseline to Week 24

Nasal Peak Inspiratory flow (nasal flow in liter per minute).

Change from baseline to Week 24 in rhinosinusitis visual analogue scale (VAS)Baseline to Week 24

Severity of the rhinosinusitis from 0 to 10. Higher scores indicate more severe symptom.

Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)Baseline to Week 36

Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).

Incidence of adverse events of special interest (AESIs)Baseline to Week 36

Incidence of adverse events of special interest (AESIs).

Trial Locations

Locations (94)

University of Texas Health Science Center- Site Number : 8400019

🇺🇸

Houston, Texas, United States

Modena Allergy + Asthma Site Number : 8400033

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La Jolla, California, United States

Cedars Sinai Medical Center Site Number : 8400026

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Los Angeles, California, United States

Asthma Allergy & Immunology Clinical Research Unit Site Number : 8400027

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Tampa, Florida, United States

Northwestern University Site Number : 8400001

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Chicago, Illinois, United States

Rush University Medical Center Site Number : 8400035

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Chicago, Illinois, United States

Advanced ENT and Allergy Site Number : 8400013

🇺🇸

Louisville, Kentucky, United States

University of Missouri Health Care - University Hospital Site Number : 8400016

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Columbia, Missouri, United States

Northwell Health Site Number : 8400044

🇺🇸

Great Neck, New York, United States

University of Rochester Site Number : 8400015

🇺🇸

Rochester, New York, United States

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University of Texas Health Science Center- Site Number : 8400019
🇺🇸Houston, Texas, United States

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