EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients (EVEREST)

• ClinicalTrials.gov Identifier: NCT04998604
• Recruitment Status: Recruiting
• First Posted: August 10, 2021
• Last Update Posted: February 16, 2023
• Sponsor: Sanofi
• Collaborator: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: August 9, 2021
• First Posted Date: August 10, 2021
• Last Update Posted Date: February 16, 2023
• Actual Study Start Date: September 27, 2021
• Estimated Primary Completion Date: October 17, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 9, 2021)

• Change from baseline to Week 24 in Nasal Polyp Score (NPS) [ Time Frame: 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) [ Time Frame: Baseline to Week 24 ]
  The UPSIT score ranges from 0 to 40, with 40 being the best possible score.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 14, 2023)

• Change from baseline to Week 24 in the loss of smell score of the CRSwNP Nasal Symptom Diary [ Time Frame: Baseline 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 Diary [ Time Frame: Baseline to week 24 ]
  NC scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms').
• Change from baseline to Week 24 in pre--bronchodilator forced expiratory volume in 1 second (FEV1) [ Time Frame: Baseline to Week 24 ]
  Pre-bronchodilator forced expiratory volume in 1 second (volume of air in liters).
• Change from baseline to Week 24 in Total Symptom Score (TSS) derived from the CRSwNP Nasal Symptom Diary [ Time Frame: Baseline 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) and [ Time Frame: Baseline 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 score [ Time Frame: Baseline 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) [ Time Frame: 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) [ Time Frame: Baseline to Week 24 ]
  Severity of the rhinosinusitis from 0 to 10. Higher scores indicate more severe symptom.
• Change from baseline to Week 24 in 7-item Asthma Control Questionnaire (ACQ-7) [ Time Frame: Baseline to Week 24 ]
  Asthma control with 6 questions plus FEV1 measure. Score ranges from 0 (totally controlled) and 6 (severely uncontrolled). Higher score indicates lower asthma control.
• Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: Baseline to Week 36 ]
  Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
• Incidence of adverse events of special interest (AESIs) [ Time Frame: Baseline to Week 36 ]
  Incidence of adverse events of special interest (AESIs).

Original Secondary Outcome Measures (submitted: August 9, 2021)

• Change from baseline to Week 24 in the loss of smell score of the CRSwNP Nasal Symptom Diary [ Time Frame: Baseline 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 Diary [ Time Frame: Baseline to week 24 ]
  NC scores are scored from 0 ('No symptoms') to 3 ('Severe symptoms').
• Change from baseline to Week 24 in pre-bronchodilator forced expiratory volume in 1 second (FEV1) [ Time Frame: Baseline to Week 24 ]
  Pre-bronchodilator forced expiratory volume in 1 second (volume of air in liters).
• Change from baseline to Week 24 in Total Symptom Score (TSS) derived from the CRSwNP Nasal Symptom Diary [ Time Frame: Baseline 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) and [ Time Frame: Baseline 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 score [ Time Frame: Baseline 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) [ Time Frame: 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) [ Time Frame: Baseline to Week 24 ]
  Severity of the rhinosinusitis from 0 to 10. Higher scores indicate more severe symptom.
• Change from baseline to Week 24 in 7-item Asthma Control Questionnaire (ACQ-7) [ Time Frame: Baseline to Week 24 ]
  Asthma control with 6 questions plus FEV1 measure. Score ranges from 0 (totally controlled) and 6 (severely uncontrolled). Higher score indicates lower asthma control.
• Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [ Time Frame: Baseline to Week 36 ]
  Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).
• Incidence of adverse events of special interest (AESIs) [ Time Frame: Baseline to Week 36 ]
  Incidence of adverse events of special interest (AESIs).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: EValuating trEatment RESponses of Dupilumab Versus Omalizumab in Type 2 Patients
• Official Title: A Randomized, Double-blind, Head-to-head Comparison of Dupilumab Versus Omalizumab in Severe Chronic Rhinosinusitis With Nasal Polyps (CRSwNP) and Comorbid Asthma Patients

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 CRSwNP symptoms at Week 24 compared to omalizumab
• To evaluate the efficacy of dupilumab in improving lung function 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 effect of dupilumab on asthma control 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.
• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:

Placebo injections will be administered as needed to blind the number of active dupilumab and omalizumab injections

Primary Purpose: Treatment

Condition

• Chronic Rhinosinusitis With Nasal Polyps
• Asthma

Intervention

• Drug: Dupilumab
  solution for injection subcutaneous
  Other Name: SAR231893 Dupixent
• Drug: Omalizumab
  solution for injection subcutaneous
  Other Name: Xolair
• Drug: Placebo
  solution for injection subcutaneous

Study Arms

• Experimental: Dupilumab
  Dosing every 2 weeks (Q2W)
  Interventions:

  • Drug: Dupilumab
  • Drug: Placebo
• Experimental: Omalizumab
  Dosing Q2W or every 4 weeks (Q4W)
  Interventions:

  • Drug: Omalizumab
  • Drug: Placebo

• Publications *: De Prado Gomez PharmD MSc L, Khan Mbbs Mph AH, Peters Md AT, Bachert Md PhD C, Wagenmann Md M, Heffler Md PhD E, Hopkins BMBCh C, Hellings Md PhD PW, Zhang PhD M, Xing PhD J, Rowe Md P, Jacob-Nara Md Mph DHSc JA. Efficacy and Safety of Dupilumab Versus Omalizumab in Chronic Rhinosinusitis With Nasal Polyps and Asthma: EVEREST Trial Design. Am J Rhinol Allergy. 2022 Nov;36(6):788-795. doi: 10.1177/19458924221112211. Epub 2022 Jul 15.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 9, 2021): 422
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 7, 2024
• Estimated Primary Completion Date: October 17, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Trial Transparency email recommended (Toll free number for US & Canada); 800-633-1610 ext option 6; Contact-US@sanofi.com

• Listed Location Countries: Belgium, Czechia, Denmark, Finland, France, Germany, Hungary, Italy, Poland, Portugal, Romania, Spain, Sweden, United Kingdom, United States

Administrative Information

• NCT Number: NCT04998604
• Other Study ID Numbers: LPS16747; 2021-000829-27 ( EudraCT Number ); U1111-1255-4713 ( Registry Identifier: ICTRP )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

• Current Responsible Party: Sanofi
• Original Responsible Party: Same as current
• Current Study Sponsor: Sanofi
• Original Study Sponsor: Same as current
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Not Provided
• PRS Account: Sanofi
• Verification Date: February 13, 2023