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

Phase 2
Recruiting
Conditions
Chronic Rhinosinusitis With Nasal Polyps
Interventions
Drug: placebo
Registration Number
NCT06454240
Lead Sponsor
Sanofi
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
80
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 2lunsekimigParticipant will receive lunsekimig subcutaneous (SC) every 4 weeks and intranasal mometasone furoate nasal spray (MFNS) for 24 weeks.
Arm 1placeboParticipant will receive placebo subcutaneous (SC) every 4 weeks and intranasal mometasone furoate nasal spray (MFNS) for 24 weeks.
Primary Outcome Measures
NameTimeMethod
Change in bilateral endoscopic nasal polyp score (NPS).From baseline to Week 24

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.

Secondary Outcome Measures
NameTimeMethod
Change in patient-reported total symptom score (nasal congestion/obstruction, anterior or posterior rhinorrhea, and loss of smell).From baseline to Week 24

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

Serum lunsekimig concentrationsFrom baseline to end of study (approximately 36 weeks)
Incidence of participants with treatment-emergent adverse events (TEAEs)From baseline to end of study (approximately 36 weeks)
Change in asthma control questionnaire (ACQ-5)From baseline to Week 24

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

Change in pre-bronchodilator forced expiratory volume in the first second (pre-BD FEV1)From baseline to Week 24
Change in the percent of maxillary sinus volume occupied by disease on CT scan.From baseline to Week 24
Change in patient-reported anterior rhinorrhea and posterior rhinorrhea scoreFrom baseline to Week 24

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

Change in rhinosinusitis visual analog scale (VAS).From baseline to Week 24

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.

Anti-drug antibodies (ADA) against lunsekimigFrom baseline to end of study (approximately 36 weeks)
Incidence of participants with serious adverse events (SAEs)From baseline to end of study (approximately 36 weeks)
Change in patient-reported nasal congestion/obstruction scoreFrom baseline to Week 24

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

Change in Lund-Mackay CT scoreFrom baseline to Week 24

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.

Change in SNOT-22 total score.From baseline to Week 24

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).

Change in University of Pennsylvania Smell Identification Test (UPSIT) score.From baseline to Week 24

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.

Change in pre-BD percent predicted FEV1From baseline to Week 24
Change in patient-reported loss of smell scoreFrom baseline to Week 24

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

Incidence of participants with adverse events of special interest (AESI)From baseline to end of study (approximately 36 weeks)

Trial Locations

Locations (27)

Modena Allergy + Asthma Site Number : 8400005

🇺🇸

La Jolla, California, United States

United Gastroenterologists - Murrieta- Site Number : 8400021

🇺🇸

Murrieta, California, United States

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

🇺🇸

Roseville, 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

The Allergy Group - Asthma & Allergy Boise- Site Number : 8400002

🇺🇸

Boise, Idaho, United States

Harvard Medical School - Brigham and Women's Hospital Site Number : 8400016

🇺🇸

Boston, Massachusetts, United States

Vital Prospects Clinical Research Institute - Tulsa- Site Number : 8400010

🇺🇸

Tulsa, Oklahoma, United States

Essential Medical Research- Site Number : 8400020

🇺🇸

Tulsa, Oklahoma, United States

Gary Gross Pharmaceutical Research & Consulting, Inc. Site Number : 8400004

🇺🇸

Dallas, Texas, United States

The University of Texas Health Science Center- Site Number : 8400017

🇺🇸

Houston, Texas, United States

Berkson Medical Site Number : 8400014

🇺🇸

McKinney, Texas, United States

Alamo ENT Associates Site Number : 8400001

🇺🇸

San Antonio, Texas, United States

Advanced Research Institute - Odgen- Site Number : 8400022

🇺🇸

Ogden, Utah, United States

Investigational Site Number : 0320002

🇦🇷

Rosario, Santa Fe, Argentina

Investigational Site Number : 0320001

🇦🇷

Buenos Aires, Argentina

Investigational Site Number : 0320003

🇦🇷

Mendoza, Argentina

Investigational Site Number : 0560002

🇧🇪

Gent, Belgium

Investigational Site Number : 0560001

🇧🇪

Leuven, Belgium

Investigational Site Number : 1000001

🇧🇬

Sofia, Bulgaria

Investigational Site Number : 6160002

🇵🇱

Krakow, Malopolskie, Poland

Investigational Site Number : 6160003

🇵🇱

Katowice, Slaskie, Poland

Investigational Site Number : 6160004

🇵🇱

Poznan, Poland

Investigational Site Number : 6160007

🇵🇱

Wroclaw, Poland

Investigational Site Number : 8260004

🇬🇧

Gloucester, Gloucestershire, United Kingdom

Investigational Site Number : 8260003

🇬🇧

Manchester, United Kingdom

Investigational Site Number : 8260001

🇬🇧

Newcastle Upon Tyne, United Kingdom

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