A Proof-of-Concept Study to Assess the Efficacy, Safety and Tolerability of Itepekimab (Anti--IL-33 mAb) in Participants With Chronic Rhinosinusitis Without Nasal Polyps
- Conditions
- Chronic Rhinosinusitis Without Nasal Polyps
- Interventions
- Registration Number
- NCT06691113
- Lead Sponsor
- Sanofi
- Brief Summary
ACT18421 is a multinational, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 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 in male and female participants with chronic rhinosinusitis without nasal polyps (CRSsNP) aged 18 years of age and older.
Study details include:
* The study duration (4-week screening, 24--week intervention, 20--week safety followup) will be 48 weeks.
* The intervention duration will be 24 weeks.
* The number of visits will be 7 site visits and 8 phone/remote visits.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
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Participant must be 18 years of age or older.
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Participants must have ongoing symptoms of nasal congestion/obstruction at least 12 consecutive weeks before Visit 1 and a Nasal Congestion Score (NCS) ≥2 at Visit 1 (day score) and Visit 2 (weekly average score).
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Participants must have sinus Total Symptom Score (sTSS) (NC, rhinorrhea, facial pain/pressure) ≥5 at Visit 1 (day score) and Visit 2 (weekly average score).
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Participants must have at least one of the following features:
- Prior sinonasal surgery (as protocol defined) for chronic rhinosinusitis (CRS).
- Treatment with systemic corticosteroid(s) (SCS) within the prior 2 years before Screening (Visit 1)
- Worsening symptoms of CRS in the past 2 years which would have required treatment with SCS, however participant is intolerant or has a contraindication to SCS.
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Participants must have bilateral inflammation of paranasal sinuses with bilateral ethmoid and maxillary opacification on screening CT scan. Participants must have ≥25% opacification of the ethmoid sinuses and ≥25% opacification of at least 1 maxillary sinus by central reading of CT scan.
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Participants must have a Sino-Nasal Outcome Test-22-Items (SNOT-22) score of ≥20 at Visit 1 and Visit 2.
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Participants who have received a stable dose of mometasone furoate nasal spray (MFNS) for at least 3 weeks before Visit 2.
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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).
Participants are excluded from the study if any of the following criteria apply:
- 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).
- Radiological suspicion or confirmed invasive or expansive fungal rhinosinusitis.
- Have any clinically significant diseases or disorders (eg, cardiovascular, pulmonary, gastrointestinal, liver, kidney, neurological, musculoskeletal, endocrine, metabolic, psychiatric, physical impairment) that, in the opinion of the Investigator, may put the subject at risk by participating in the study, or interfere with the subject's intervention, assessment, or influence the results of the study, or have compliance issues with the study.
- Sinus surgery within 6 months before Screening (Visit 1)
- Participants who received SCS 1 month prior to Screening (Visit 1) or during the screening period (between Visit 1 and Visit 2).
- Participants treated with other intranasal corticosteroid(s) (INCS) (only study provided AxMP [MFNS] is permitted), intranasal emitting devices/stents, nasal spray using exhalation delivery system such as Xhance™ during the screening period.
- Participants with a history of severe systemic hypersensitivity reaction to mAb.
- Known allergy to itepekimab or to its excipients. Any drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study.
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
Group Intervention Description Itepekimab low dose Itepekimab (SAR440340) SC administration of Itepekimab low dose for 24 weeks Itepekimab high dose Itepekimab (SAR440340) Subcutaneous (SC) administration of Itepekimab high dose for 24 weeks Itepekimab high dose Mometasone furoate nasal spray (MFNS) Subcutaneous (SC) administration of Itepekimab high dose for 24 weeks Itepekimab low dose Placebo SC administration of Itepekimab low dose for 24 weeks Itepekimab low dose Mometasone furoate nasal spray (MFNS) SC administration of Itepekimab low dose for 24 weeks Placebo Placebo SC administration of matching placebo for 24 weeks Placebo Mometasone furoate nasal spray (MFNS) SC administration of matching placebo for 24 weeks
- Primary Outcome Measures
Name Time Method Change from baseline in sinus (maxillary, ethmoid) percent opacification volume assessed by CT scan Baseline to End of Treatment (EOT) (Week 24) Change from baseline in sinus inflammation as assessed by Computerized Tomography (CT) scan of the sinuses in the itepekimab-- compared to placebo-- treated study participants on the background of intranasal corticosteroid (INCS).
- Secondary Outcome Measures
Name Time Method Change from baseline in the sTSS Baseline to EOT (Week 24) The CRSsNP sinus Total Symptom Score (sTSS) is a composite score derived from nasal congestion (NC), anterior/posterior rhinorrhea, and facial pain/pressure. The total score ranges from 0 to 9 with higher scores indicating greater overall symptom severity.
Change from baseline in nasal congestion (NC) severity score using the CRSsNP daily ediary Baseline to EOT (Week 24) The CRSsNP sinonasal symptom diary is designed to assess the severity of 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.
Change from baseline in anterior/posterior rhinorrhea severity score using the CRSsNP daily ediary Baseline to EOT (Week 24) The CRSsNP sinonasal symptom diary is designed to assess the severity of 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.
Change from baseline in facial pain/pressure severity score using the CRSsNP daily ediary Baseline to EOT (Week 24) The CRSsNP sinonasal symptom diary is designed to assess the severity of 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.
Change from baseline in loss of smell severity score using the CRSsNP daily ediary Baseline to EOT (Week 24) The CRSsNP sinonasal symptom diary is designed to assess the severity of 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.
Change from baseline in SNOT-22 total score Baseline to EOT (Week 24) The Sino-Nasal Outcome Test-22-Items (SNOT-22) is a patient-reported outcome questionnaire designed to assess the impact of chronic rhinosinusitis (CRS) on patients' Health-Related Quality of Life (HRQoL). It has 22 items covering symptoms, social/emotional impact, productivity, and sleep consequences of CRS. A global score ranges from 0 to 110 with higher score indicating greater rhinosinusitis-related health burden.
Change from baseline in sinus opacification as measured by the Lund-Mackay (LMK) score and the modified LMK score Baseline to EOT (Week 24) The LMK and the modified LMK scoring systems are based on points given for degree of opacification, which are 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.
Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent adverse events of special interest (TEAESIs), treatment emergent serious adverse events (TESAEs), and TEAEs leading to intervention discontinuation Baseline up to End of Study (EOS) (Week 44) Itepekimab concentration in serum Baseline to EOS (Week 44) Incidence of treatment-emergent (TE) anti-itepekimab antibodies responses Baseline to EOS (Week 44)
Trial Locations
- Locations (53)
Investigational Site Number : 1520002
🇨🇱Concepción, Biobío, Chile
Alabama Allergy & Asthma Center - Birmingham - Brookwood Boulevard- Site Number : 8400006
🇺🇸Birmingham, Alabama, United States
Western States Clinical Research- Site Number : 8400009
🇺🇸Wheat Ridge, Colorado, United States
Advanced Research Associates (ARA) Professionals- Site Number : 8400002
🇺🇸Miami, Florida, United States
Modena Allergy + Asthma- Site Number : 8400005
🇺🇸La Jolla, California, United States
Sacramento Ear Nose & Throat - Roseville- Site Number : 8400008
🇺🇸Roseville, California, United States
United Gastroenterologists - Murrieta- Site Number : 8400001
🇺🇸Murrieta, California, United States
Treasure Valley Medical Research- Site Number : 8400022
🇺🇸Boise, Idaho, United States
ENT Associates of Texas - McKinne- Site Number : 8400013
🇺🇸McKinney, Texas, United States
Alamo ENT Associates- Site Number : 8400026
🇺🇸San Antonio, Texas, United States
Investigational Site Number : 0320003
🇦🇷San Miguel de Tucumán, Tucumán, Argentina
Investigational Site Number : 0320001
🇦🇷Buenos Aires, Argentina
Investigational Site Number : 0560002
🇧🇪Gent, Belgium
Investigational Site Number : 0560001
🇧🇪Leuven, Belgium
Investigational Site Number : 1240005
🇨🇦London, Ontario, Canada
Investigational Site Number : 1240002
🇨🇦Montreal, Quebec, Canada
Investigational Site Number : 1240001
🇨🇦Québec City, Quebec, Canada
Investigational Site Number : 1240003
🇨🇦Québec City, Quebec, Canada
Investigational Site Number : 1240012
🇨🇦Québec City, Quebec, Canada
Investigational Site Number : 1240009
🇨🇦Trois-rivières, Quebec, Canada
Investigational Site Number : 1520001
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1520003
🇨🇱Santiago, Reg Metropolitana De Santiago, Chile
Investigational Site Number : 1560004
🇨🇳Baotou, China
Investigational Site Number : 1560002
🇨🇳Shanghai, China
Investigational Site Number : 1560003
🇨🇳Zibo, China
Investigational Site Number : 1560001
🇨🇳Beijing, China
Investigational Site Number : 2500012
🇫🇷La Rochelle, France
Investigational Site Number : 2500004
🇫🇷Marseille, France
Investigational Site Number : 2500005
🇫🇷Montpellier, France
Investigational Site Number : 2500010
🇫🇷Poitiers, France
Azienda Ospedaliero-Universitaria Pisana-Site Number : 3800003
🇮🇹Pisa, Italy
Fondazione Policlinico Universitario Campus Bio-Medico-Site Number : 3800002
🇮🇹Roma, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Site Number : 3800001
🇮🇹Roma, Italy
Investigational Site Number : 4100005
🇰🇷Cheonan-si, Chungcheongnam-do, Korea, Republic of
Investigational Site Number : 4100003
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100004
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100002
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 4100001
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Investigational Site Number : 6160008
🇵🇱Lodz, Lódzkie, Poland
Investigational Site Number : 6160001
🇵🇱Warsaw, Mazowieckie, Poland
Investigational Site Number : 6160004
🇵🇱Bielsko-Biala, Poland
Investigational Site Number : 6160006
🇵🇱Krakow, Poland
Investigational Site Number : 6160002
🇵🇱Poznan, Poland
Investigational Site Number : 6200001
🇵🇹Guimaraes, Portugal
Investigational Site Number : 6200002
🇵🇹Porto, Portugal
Investigational Site Number : 6420001
🇷🇴Brașov, Romania
Investigational Site Number : 6420002
🇷🇴Bucharest, Romania
Investigational Site Number : 7240003
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 7240002
🇪🇸L'hospitalet de Llobregat, Catalunya [Cataluña], Spain
Investigational Site Number : 7240004
🇪🇸Jerez de La Frontera, Cádiz, Spain
Investigational Site Number : 7240005
🇪🇸Pamplona, Navarra, Spain
Investigational Site Number : 7240001
🇪🇸Seville, Sevilla, Spain
Investigational Site Number : 7240006
🇪🇸Madrid, Spain