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

Sanofi

Status and phase: Active, not recruiting; Phase 4

Conditions: Asthma; Chronic Rhinosinusitis With Nasal Polyps

Treatments: Drug: Omalizumab; Drug: Placebo; Drug: Dupilumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04998604

U1111-1255-4713 (Registry Identifier)

LPS16747

2021-000829-27 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 320 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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320 participants in 2 patient groups

Dupilumab

Experimental group

Description:

Dosing every 2 weeks (Q2W)

Treatment:

Drug: Dupilumab

Drug: Placebo

Omalizumab

Experimental group

Description:

Dosing Q2W or every 4 weeks (Q4W)

Treatment:

Drug: Placebo

Drug: Omalizumab