Clinical trial NCT06691113: 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
Official title: A Randomized, Double-blind, Placebo-controlled, Proof-of-Concept (PoC) Study to Assess the Efficacy, Safety and Tolerability of Itepekimab in Participants With Inadequately Controlled Chronic Rhinosinusitis Without Nasal Polyps
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Rhinosinusitis Without Nasal Polyps
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2024-11-15
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Participant must be 18 years of age or older.
* 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).
* 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).
* 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.
* 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.
* Participants must have a Sino-Nasal Outcome Test-22-Items (SNOT-22) score of ≥20 at Visit 1 and Visit 2.
* Participants who have received a stable dose of mometasone furoate nasal spray (MFNS) for at least 3 weeks before Visit 2.
* 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 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.

Primary outcomes:
measure: Change from baseline in sinus (maxillary, ethmoid) percent opacification volume assessed by CT scan
timeFrame: Baseline to End of Treatment (EOT) (Week 24)
Secondary outcomes:
measure: Change from baseline in the sTSS
timeFrame: Baseline to EOT (Week 24)
measure: Change from baseline in nasal congestion (NC) severity score using the CRSsNP daily ediary
timeFrame: Baseline to EOT (Week 24)
measure: Change from baseline in anterior/posterior rhinorrhea severity score using the CRSsNP daily ediary
timeFrame: Baseline to EOT (Week 24)
measure: Change from baseline in facial pain/pressure severity score using the CRSsNP daily ediary
timeFrame: Baseline to EOT (Week 24)
measure: Change from baseline in loss of smell severity score using the CRSsNP daily ediary
timeFrame: Baseline to EOT (Week 24)
measure: Change from baseline in SNOT-22 total score
timeFrame: Baseline to EOT (Week 24)
measure: Change from baseline in sinus opacification as measured by the Lund-Mackay (LMK) score and the modified LMK score
timeFrame: Baseline to EOT (Week 24)
measure: 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
timeFrame: Baseline up to End of Study (EOS) (Week 44)
measure: Itepekimab concentration in serum
timeFrame: Baseline to EOS (Week 44)
measure: Incidence of treatment-emergent (TE) anti-itepekimab antibodies responses
timeFrame: Baseline to EOS (Week 44)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Allergy & Asthma Center - Birmingham - Brookwood Boulevard- Site Number : 8400006
state: Alabama
city: La Jolla
country: United States
facility: Modena Allergy + Asthma- Site Number : 8400005
state: California
city: Murrieta
country: United States
facility: United Gastroenterologists - Murrieta- Site Number : 8400001
state: California
city: Roseville
country: United States
facility: Sacramento Ear Nose & Throat - Roseville- Site Number : 8400008
state: California
city: Wheat Ridge
country: United States
facility: Western States Clinical Research- Site Number : 8400009
state: Colorado
city: Miami
country: United States
facility: Advanced Research Associates (ARA) Professionals- Site Number : 8400002
state: Florida
city: Boise
country: United States
facility: Treasure Valley Medical Research- Site Number : 8400022
state: Idaho
city: McKinney
country: United States
facility: ENT Associates of Texas - McKinne- Site Number : 8400013
state: Texas
city: San Antonio
country: United States
facility: Alamo ENT Associates- Site Number : 8400026
state: Texas
city: San Miguel de Tucumán
country: Argentina
facility: Investigational Site Number : 0320003
state: Tucumán
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
city: Corrientes
country: Argentina
facility: Investigational Site Number : 0320004
city: Brussels
country: Belgium
facility: Investigational Site Number : 0560003
city: Gent
country: Belgium
facility: Investigational Site Number : 0560002
city: Gesves Namur
country: Belgium
facility: Investigational Site Number : 0560004
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: London
country: Canada
facility: Investigational Site Number : 1240005
state: Ontario
city: Montreal
country: Canada
facility: Investigational Site Number : 1240002
state: Quebec
city: Québec City
country: Canada
facility: Investigational Site Number : 1240001
state: Quebec
city: Québec City
country: Canada
facility: Investigational Site Number : 1240003
state: Quebec
city: Québec City
country: Canada
facility: Investigational Site Number : 1240012
state: Quebec
city: Trois-rivières
country: Canada
facility: Investigational Site Number : 1240009
state: Quebec
city: Concepción
country: Chile
facility: Investigational Site Number : 1520002
state: Biobío
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520003
state: Reg Metropolitana De Santiago
city: Baotou
country: China
facility: Investigational Site Number : 1560004
city: Beijing
country: China
facility: Investigational Site Number : 1560001
city: Shanghai
country: China
facility: Investigational Site Number : 1560002
city: Zibo
country: China
facility: Investigational Site Number : 1560003
city: La Rochelle
country: France
facility: Investigational Site Number : 2500012
city: Marseille
country: France
facility: Investigational Site Number : 2500004
city: Montpellier
country: France
facility: Investigational Site Number : 2500005
city: Poitiers
country: France
facility: Investigational Site Number : 2500010
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana-Site Number : 3800003
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Campus Bio-Medico-Site Number : 3800002
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Site Number : 3800001
city: Cheonan-si
country: Korea, Republic of
facility: Investigational Site Number : 4100005
state: Chungcheongnam-do
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100004
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Lodz
country: Poland
facility: Investigational Site Number : 6160008
state: Lódzkie
city: Warsaw
country: Poland
facility: Investigational Site Number : 6160001
state: Mazowieckie
city: Bielsko-Biala
country: Poland
facility: Investigational Site Number : 6160004
city: Krakow
country: Poland
facility: Investigational Site Number : 6160006
city: Poznan
country: Poland
facility: Investigational Site Number : 6160002
city: Guimaraes
country: Portugal
facility: Investigational Site Number : 6200001
city: Porto
country: Portugal
facility: Investigational Site Number : 6200002
city: Brașov
country: Romania
facility: Investigational Site Number : 6420001
city: Bucharest
country: Romania
facility: Investigational Site Number : 6420002
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240003
state: Barcelona [Barcelona]
city: L'hospitalet de Llobregat
country: Spain
facility: Investigational Site Number : 7240002
state: Catalunya [Cataluña]
city: Jerez de La Frontera
country: Spain
facility: Investigational Site Number : 7240004
state: Cádiz
city: Pamplona
country: Spain
facility: Investigational Site Number : 7240005
state: Navarra
city: Seville
country: Spain
facility: Investigational Site Number : 7240001
state: Sevilla
city: Madrid
country: Spain
facility: Investigational Site Number : 7240006
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: