A Proof-of-concept Study of Lunsekimig Compared With Placebo in Adults With Chronic Rhinosinusitis With Nasal Polyps

Phase 2Active Not RecruitingNCT06454240

Sanofi79 enrolled

Overview

This is a parallel, Phase 2, 2-arm, multicenter, randomized, double-blind, placebo-controlled, proof-of-concept study for treatment of CRSwNP. The purpose of this study is to assess the efficacy, safety, and tolerability of add-on therapy with subcutaneous lunsekimig in adult participants (aged 18 to 70 years, inclusive) with CRSwNP who are inadequately controlled on intranasal corticosteroid treatment. Participants with and without co-morbid asthma will be included in the study, and lung function will be assessed in both groups. The study duration will be up to approximately 40 weeks per participant, including 4 weeks of screening run-in period, 24 weeks of intervention period, and 12 weeks of follow-up.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Chronic Rhinosinusitis With Nasal Polyps

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: \- A minimum bilateral nasal polyp score of 5 out of a maximum score of 8 for both nostrils (with at least a score of 2 for each nostril) despite use of intranasal corticosteroid treatment for at least 2 months prior to screening Ongoing symptoms for at least 2 months prior to screening, including: * Nasal congestion, blockage, or obstruction with moderate or severe symptom severity at screening (Score 2 or 3 on NC Score) and a weekly average severity score of at least 1 (range 0 to 3) at randomization (NC Score: 0=no symptoms, 1=mild, 2=moderate, and 3=severe). * At least 1 of the following 2 symptoms: (1) partial loss of smell (hyposmia) or total loss of smell (anosmia); (2) anterior and/or posterior rhinorrhea. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: * Patient who has received any therapies such as for example systemic corticosteroids, anti-IgE therapy, monoclonal antibody and some others in the specified timeframe(s) prior to the screening visit * Patients who have undergone any nasal/sinus surgery within 6 months before screening or for whom NPS cannot be determined accurately on endoscopy due to anatomic changes to the nasal cavity from past nasal/sinus surgery * Patients with conditions/concomitant diseases making them non evaluable for the primary efficacy endpoint * Signs or a CT scan suggestive of Allergic fungal rhinosinusitis * Active/chronic helminthic infection * History of human immunodeficiency virus (HIV) infection or positive HIV screen (Anti-HIV- and HIV-2 antibodies) at screening visit * Patients with positive or indeterminate hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody at screening visit NOTE: The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial

Locations (29)

Allergy & Rheumatology- Site Number : 8400005

La Jolla, California, United States

Sacramento Ear Nose & Throat - Roseville- Site Number : 8400003

Roseville, California, United States

Senta Clinic- Site Number : 8400025

San Diego, California, United States

James A Haley Veterans' Hospital- Site Number : 8400015

Tampa, Florida, United States

Emory University Hospital Midtown- Site Number : 8400012

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

Change in bilateral endoscopic nasal polyp score (NPS).

This score (NPS) is the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. NP is graded based on polyp size where: 0- no polyps and 4- large polyps causing complete obstruction of the inferior nasal cavity.

Time frame: From baseline to Week 24

Secondary Outcomes

Change in patient-reported nasal congestion/obstruction score

Patient-reported nasal congestion/obstruction score. Score is using a 0-3 categorical scale where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms

Time frame: From baseline to Week 24

Change in Lund-Mackay CT score

Lund-Mackay system is based on scoring bilateral areas of opacification with points given for degree of sinus opacification in each reagion: 0 = normal, 1 = partial opacification, 2 = total opacification.

Time frame: From baseline to Week 24

Change in the percent of maxillary sinus volume occupied by disease on CT scan.

Time frame: From baseline to Week 24

Change in SNOT-22 total score.

The SNOT-22 is a 22-item health-related outcomes assessment. The 22-question SNOT-22 is scored as 0 (no problem) to 5 (problem as bad as it can be) with a total range from 0 to 110 (higher scores indicate poorer outcomes).

Time frame: From baseline to Week 24

Change in patient-reported total symptom score (nasal congestion/obstruction, anterior or posterior rhinorrhea, and loss of smell).

Score is using a 0-3 categorical scale where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms

Time frame: From baseline to Week 24

Change in patient-reported anterior rhinorrhea and posterior rhinorrhea score

0-3 scale, component of patient-reported total symptom score

Time frame: From baseline to Week 24

Change in rhinosinusitis visual analog scale (VAS).

The VAS for rhinosinusitis is used to evaluate the total severity (30). Rhinosinusitis disease can be divided into Mild, Moderate and Severe based on total severity VAS score (0 to 10 cm): * MILD = VAS 0 to 3. * MODERATE = VAS \>3 to 7. * SEVERE = VAS \>7 to 10. The participant is asked to indicate along a 10 centimeter straight horizontal line (VAS) the answer to the question: "How troublesome are your symptoms of your rhinosinusitis". The VAS ranks from 0 (Not troublesome) to 10 (Worst thinkable troublesome) and is measured in centimeters.

Time frame: From baseline to Week 24

Change in University of Pennsylvania Smell Identification Test (UPSIT) score.

The UPSIT test is a rapid and easy-to-administer method to quantitatively assess human olfactory function. The test consists of four booklets, each containing 10 odorants with one odorant per page. Above each odorant strip is a multiple-choice question with four alternative words to describe the odour. Score depends on the amount of answers out of 40 possible correct answers.

Time frame: From baseline to Week 24

Change in patient-reported loss of smell score

0-3 scale, component of patient-reported total symptom score

Time frame: From baseline to Week 24

Serum lunsekimig concentrations

Time frame: From baseline to end of study (approximately 36 weeks)

Anti-drug antibodies (ADA) against lunsekimig

Time frame: From baseline to end of study (approximately 36 weeks)

Incidence of participants with treatment-emergent adverse events (TEAEs)

Time frame: From baseline to end of study (approximately 36 weeks)

Incidence of participants with adverse events of special interest (AESI)

Time frame: From baseline to end of study (approximately 36 weeks)

Incidence of participants with serious adverse events (SAEs)

Time frame: From baseline to end of study (approximately 36 weeks)

Change in asthma control questionnaire (ACQ-5)

ACQ-5 is Asthma control questionnaire assessing symptoms. Lower score shows better asthma control

Time frame: From baseline to Week 24

Change in pre-bronchodilator forced expiratory volume in the first second (pre-BD FEV1)

Time frame: From baseline to Week 24

Change in pre-BD percent predicted FEV1

Time frame: From baseline to Week 24