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

A Randomized Phase 2, Double-blind, Placebo-controlled, Parallel-group, 2-arm Study to Assess the Efficacy, Safety, and Tolerability of Subcutaneous Lunsekimig in Adult Participants With Chronic Rhinosinusitis With Nasal Polyps (CRSwNP)

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 Overview

• Status: Completed
• Conditions: Chronic Rhinosinusitis With Nasal Polyps
• Intervention / Treatment: Drug: placebo; Drug: lunsekimig

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1121
    • Investigational Site Number : 0320001
  • Mendoza, Argentina, 5500
    • Investigational Site Number : 0320003
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, 2000
      • Investigational Site Number : 0320002
• Belgium
  • Ghent, Belgium, 9000
    • Investigational Site Number : 0560002
  • Leuven, Belgium, 3000
    • Investigational Site Number : 0560001
• Bulgaria
  • Sofia, Bulgaria, 1612
    • Investigational Site Number : 1000001
• Poland
  • Poznan, Poland, 60-693
    • Investigational Site Number : 6160004
  • Wroclaw, Poland, 53-034
    • Investigational Site Number : 6160007
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-033
      • Investigational Site Number : 6160002
  • Masovian Voivodeship
    • Warsaw, Masovian Voivodeship, Poland, 00-909
      • Investigational Site Number : 6160001
    • Warsaw, Masovian Voivodeship, Poland, 02-507
      • Investigational Site Number : 6160005
  • Silesian Voivodeship
    • Katowice, Silesian Voivodeship, Poland, 40-611
      • Investigational Site Number : 6160003
• United Kingdom
  • Manchester, United Kingdom, M13 9wl
    • Investigational Site Number : 8260003
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Investigational Site Number : 8260001
  • Gloucestershire
    • Gloucester, Gloucestershire, United Kingdom, GL1 3NN
      • Investigational Site Number : 8260004
• United States
  • California
    • La Jolla, California, United States, 92037
      • Allergy & Rheumatology- Site Number : 8400005
    • Roseville, California, United States, 95661
      • Sacramento Ear Nose & Throat - Roseville- Site Number : 8400003
    • San Diego, California, United States, 92018
      • Senta Clinic- Site Number : 8400025
  • Florida
    • Tampa, Florida, United States, 33612
      • James A Haley Veterans' Hospital- Site Number : 8400015
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown- Site Number : 8400012
  • Idaho
    • Boise, Idaho, United States, 83706
      • The Allergy Group - Asthma & Allergy Boise- Site Number : 8400002
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Harvard Medical School - Brigham and Women's Hospital Site Number : 8400016
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74137
      • Essential Medical Research- Site Number : 8400020
  • Texas
    • Bellaire, Texas, United States, 77401
      • McGovern Medical School - UT Physicians Dermatology - Bellaire Station- Site Number : 8400017
    • Dallas, Texas, United States, 75231
      • Gary Gross Pharmaceutical Research & Consulting, Inc. Site Number : 8400004
    • McKinney, Texas, United States, 75070
      • Berkson Medical - McKinney- Site Number : 8400014
    • San Antonio, Texas, United States, 78258
      • Alamo ENT Associates Site Number : 8400001
  • Utah
    • Ogden, Utah, United States, 84405
      • Advanced Research Institute - Odgen- Site Number : 8400022
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Eastern Virginia Medical School (EVMS) Medical Group- Site Number : 8400008

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm 1; Participant will receive placebo subcutaneous (SC) every 4 weeks and intranasal mometasone furoate nasal spray (MFNS) for 24 weeks.	Drug: placebo; Pharmaceutical form:solution for injection-Route of administration:subcutaneous
Experimental: Arm 2; Participant will receive lunsekimig subcutaneous (SC) every 4 weeks and intranasal mometasone furoate nasal spray (MFNS) for 24 weeks.	Drug: lunsekimig; Pharmaceutical form:solution for injection-Route of administration:subcutaneous; Other Names: SAR443765

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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 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).	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	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	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.	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.	From baseline to Week 24
Change in patient-reported loss of smell score	0-3 scale, component of patient-reported total symptom score	From baseline to Week 24
Serum lunsekimig concentrations		From baseline to end of study (approximately 36 weeks)
Anti-drug antibodies (ADA) against lunsekimig		From 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)
Incidence of participants with adverse events of special interest (AESI)		From 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 asthma control questionnaire (ACQ-5)	ACQ-5 is Asthma control questionnaire assessing symptoms. Lower score shows better asthma control	From baseline to Week 24
Change in pre-bronchodilator forced expiratory volume in the first second (pre-BD FEV1)		From baseline to Week 24
Change in pre-BD percent predicted FEV1		From baseline to Week 24

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

Helpful Links

• Chronic Rhinosinusitis with Nasal Polyps
• ACT18207 Plain Language Results Summary

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2024
• Primary Completion (Actual): January 29, 2026
• Study Completion (Actual): April 23, 2026

Study Registration Dates

• First Submitted: June 6, 2024
• First Submitted That Met QC Criteria: June 6, 2024
• First Posted (Actual): June 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Nose Diseases; Otorhinolaryngologic Diseases; Rhinitis; Paranasal Sinus Diseases; Rhinosinusitis; Polyps; Nasal Polyps; Sinusitis; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: ACT18207; 2024-511261-11 (Registry Identifier: CTIS); U1111-1300-6978 (Other Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No