A Phase 3 Study to Assess the Efficacy, Safety, and Tolerability of Itepekimab (Anti-IL-33 mAb) in Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps

Phase 3Active Not RecruitingNCT06834360

Sanofi216 enrolled

Overview

EFC18419 is a multinational, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 study with 3 treatment groups. The purpose of the study is to evaluate the efficacy, safety and tolerability of 2 dosing regimens of itepekimab compared to placebo as add-on therapy to intranasal corticosteroids (INCS) in male and female participants with chronic rhinosinusitis with nasal polyps (CRSwNP) aged 18 years of age and older. Study details include: * The study duration per participant (4-week screening, 52-week treatment, 20-week safety follow-up) will be up to 76 weeks. For participants transitioning to the LTS18420 study, the study duration will be 56 weeks. * The treatment duration will be up to 52 weeks. * The number of visits will be 9 site visits and 20 phone/home visits.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

216

Conditions

Chronic Rhinosinusitis With Nasal Polyps

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participants must be 18 years of age or older. * Participants with a history of chronic rhinosinusitis with nasal polyps (CRSwNP) for at least 1 year prior to screening * Participants must have at least one of the following features: * Prior sinonasal surgery for nasal polyps (NP). * Worsening symptoms of chronic rhinosinusitis (CRS) requiring treatment with systemic corticosteroid(s) (SCS) within the prior 1 year before screening (Visit 1). * An endoscopic bilateral Nasal Polyp Score (NPS) of at least 5 out of maximum score of 8 (with a minimum score of 2 in each nasal cavity) at screening and randomization. * Ongoing symptoms (for at least 12 weeks before Visit 1) of: * Nasal congestion/blockade/obstruction with moderate or severe (symptom severity score 2 or 3) at Visit 1 and a weekly average severity of greater than 1 in the week before randomization (Visit 2), AND * At least one of the following two symptoms: loss of smell or rhinorrhea (anterior/posterior). * A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: * Is not a women of childbearing potential (WOCBP), OR * Is a WOCBP and agrees to use a contraceptive method that is highly effective, with a failure rate of \<1% during the study (at a minimum until 20 weeks after the last dose of study intervention). Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: * Participants with a history of clinically significant renal, hepatic, metabolic, neurologic, hematologic, ophthalmologic, respiratory (excluding those with asthma and aspirin-exacerbated respiratory disease (AERD) which may be included in the study), gastrointestinal, cardiovascular, cerebrovascular, or other significant medical illness or disorder, which, in the judgment of the Investigator, could interfere with the study or require treatment that might interfere with the study. * Participants who are currently smoking tobacco and/or vaping, or participants in whom smoking/vaping cessation has occurred \<6 months prior to Screening (Visit 1). Nicotine replacement therapy and/or noninhaled tobacco product use are not considered current smoking of tobacco. * Participants meet any contraindications for mometasone furoate nasal spray (MFNS) such as hypersensitivity to MFNS or any of its components; or participants with uncontrolled opportunistic infections. * Participants with a history of a severe systemic hypersensitivity reaction to a mAb. * Participants with conditions/concomitant diseases making them non-evaluable at Visit 1 or for the primary efficacy endpoint. * Participants with nasal cavity malignant tumor and benign tumors (eg, papilloma, blood boil etc). * Participants with severe uncontrolled asthma with history of 2 and/or more exacerbations, requiring SCS or 1 hospitalization requiring SCS in the past year. * History of concomitant lung disease (other than asthma, eg, COPD, interstitial lung disease) which in the opinion of the Investigator could interfere with performance and interpretation of spirometry. * Participants treated with intranasal corticosteroid(s) (INCS) (MFNS is permitted), intranasal emitting devices/stents, nasal spray using exhalation delivery system such as XhanceTM during the screening period. In Japan and China INCS other than MFNS are permitted. * Participants who have undergone any sinus intranasal surgery (including polypectomy) within 6 months before Visit 1. * Participants who received SCS 1 month prior to Screening (Visit 1) or during the screening period (between Visit 1 and Visit 2). * Known allergy to itepekimab or its excipients, or any drug or other allergy that, in the opinion of the Investigator, contraindicates participation in this study. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Locations (111)

Excel ENT of Alabama- Site Number : 8400052

Birmingham, Alabama, United States

Velocity Clinical Research - San Diego- Site Number : 8400041

La Mesa, California, United States

Cedars-Sinai Medical Center- Site Number : 8400030

Los Angeles, California, United States

One Of A Kind Clinical Research Center- Site Number : 8400034

Napa, California, United States

University of Florida - Jacksonville- Site Number : 8400053

Jacksonville, Florida, United States

Outcomes

Primary Outcomes

Change from baseline in the endoscopic NPS

The Nasal Polyp Score (NPS) is the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. Nasal polyp is graded based on polyp size from 0 to 4 with higher scores indicating larger polyps. The sum of right and left nostril scores ranges from 0 (no polyps) to 8 (large polyps).

Time frame: Baseline to Week 24

Change from baseline in the NCS

The Nasal Congestion Score (NCS) is scored using a 0-3 categorical scale where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms. Outcome value is defined as the preceding 28-day average of morning scores recorded in eDiary.

Time frame: Baseline to Week 24

Secondary Outcomes

Change from baseline in endoscopic NPS

The NPS is the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. Nasal polyp is graded based on polyp size from 0 to 4 with higher scores indicating larger polyps. The sum of right and left nostril scores ranges from 0 (no polyps) to 8 (large polyps).

Time frame: Baseline to Week 52

Change from baseline in NCS

The NCS is scored using a 0-3 categorical scale where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms. Outcome value is defined as the preceding 28-day average of morning scores recorded in eDiary.

Time frame: Baseline to Week 52

Change from baseline in opacification of sinuses assessed by Computed Tomography (CT) scan using the LMK score

The Lund-Mackay (LMK) system is based on localization with points given for degree of opacification: 0 = normal, 1 = partial opacification, 2 = total opacification. These points are then applied to the maxillary, anterior ethmoid, posterior ethmoid, sphenoid, frontal sinus on each side. The osteomeatal complex is graded as 0 = not occluded, or 2 = occluded, deriving a maximum score of 12 per side. The total score is the sum of scores from each side and ranges from 0 (normal) to 24 (total opacification).

Time frame: Baseline to Week 24

Change from baseline in the TSS (nasal congestion/obstruction, anterior/posterior rhinorrhea, and loss of sense of smell)

The CRSwNP Total Symptom Score (TSS) is a composite score derived from nasal congestion (NC)/obstruction, anterior/posterior rhinorrhea, and loss of smell. The total score ranges from 0 to 9 with higher scores on TSS indicating greater overall symptom severity.

Time frame: Baseline to Weeks 24 and 52

Change from baseline in loss of smell severity score using the daily CRSwNP sinonasal symptom eDiary, and UPSIT score

The CRSwNP sinonasal symptom diary is designed to assess the severity of chronic rhinosinusitis (CRS) sinonasal symptoms on daily basis. These symptoms include NC/obstruction, anterior rhinorrhea and posterior rhinorrhea, facial pain/pressure, loss of smell, and headache. Each of the individual items of the diary are scored from 0 ("No symptoms") to 3 ("Severe symptoms - symptoms that are hard to tolerate, cause interference with activities or daily living"). Higher scores on the items of the individual symptoms denote greater symptom severity. The University of Pennsylvania Smell Identification Test (UPSIT) test is a rapid and easy-to-administer method to quantitatively assess human olfactory function. The total score ranges from 0 (anosmia) to 40 (normosmia).

Time frame: Baseline to Weeks 24 and 52

Change from baseline in SNOT-22 total score

The Sino-Nasal Outcome Test-22-Items (SNOT-22) is a patient-reported outcome questionnaire designed to assess the impact of CRS on patient's Health-Related Quality of Life (HRQoL). It has 22 items covering five domains: Nasal, Ear/Facial, Sleep, Function, and Emotion. A global score ranging from 0 to 110 with higher score indicating greater rhinosinusitis related health burden.

Time frame: Baseline to Weeks 24 and 52

Change from baseline in PROMIS SD-SF-8b scores

The Patient Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance - Short Form 8b (SD-SF-8b) is a generic 8-item sleep disturbance assessment that evaluates difficulties with falling asleep, staying asleep, and getting enough sleep; and perceptions on the quality and satisfaction of sleep. Scores are calculated with a conversion of the raw score (score range 8 to 40) into a standardized T-score with the mean of the 50 and SD of 10, where higher scores indicate more disturbed sleep.

Time frame: Baseline to Weeks 24 and 52

Proportion of participants with CRSwNP requiring systemic corticosteroid(s) (SCS) or surgery for CRS

Time frame: Baseline up to Week 52

Annualized rate of SCS course or surgery for CRS

Time frame: Baseline up to Week 52

Time to first either SCS or surgery for CRS

Time frame: Baseline through Week 52

Change from baseline in pre-BD FEV1 (in mL) in participants with co-morbid asthma

Pre-BD FEV1: pre-bronchodilator forced expiratory volume in 1 second

Time frame: Baseline to Weeks 24 and 52

Change from baseline in ACQ-5 score in participants with co-morbid asthma

The Asthma Control Questionnaire (ACQ) is a questionnaire that measures the adequacy of asthma control and any changes in asthma control that may occur spontaneously or as a result of treatment. The ACQ-5 has 5 questions on the asthma symptoms. The global score is the mean of the item responses and ranges from 0 and 6 with higher score indicating lower asthma control.

Time frame: Baseline to Weeks 24 and 52

Change from the baseline in NPS and NCS in the subgroup of patients with aspirin-exacerbated respiratory disease (AERD)

Time frame: Baseline to Weeks 24 and 52

Proportion of participants with AERD requiring SCS or surgery for CRS

Time frame: Baseline up to Week 52

Annualized rate of SCS course or surgery for CRS in participants with AERD

Time frame: Baseline up to Week 52

Time to first either SCS or surgery for CRS in participants with AERD

Time frame: Baseline through Week 52

Change from baseline in pre-BD FEV1 (in ml) in participants with AERD

Pre-BD FEV1: pre-bronchodilator forced expiratory volume in 1 second

Time frame: Baseline to Weeks 24 and 52

Proportion of NPS responders (defined as participants with improvement by at least 1 point in NPS)

Time frame: Weeks 24 and 52

Proportion of NPS responders (defined as participants with improvement by at least 2 points in NPS)

Time frame: Weeks 24 and 52

Incidence of treatment-emergent adverse Events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment-emergent adverse events of special interest (TEAESIs) and TEAEs leading to treatment discontinuation

Time frame: Baseline to End of Study (EOS) (Week 72)

Itepekimab concentration in serum

Time frame: Baseline to EOS (Week 72)

Incidence of treatment-emergent anti-itepekimab antibody (ADA) responses

Time frame: Baseline to EOS (Week 72)