Chronic rhinosinusitis with nasal polyps
Conditions
Interventions
Drug: Itepekimab (SAR440340/REGN3500)
Pharmaceutical form: Solution for injection in prefilled syringe.
Route of administration: Subcutaneous (SC) injection
Drug: Placebo matching Itepekimab
Pharm
Sponsors
Obara Kentaro
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: - Participants must be 18 years of age or older - Participants with a history of chronic rhinosinusitis with nasal polyps (CRSwNP) for at least 1 year prior to screening - Participants must have at least one of the following features: - - Prior sinonasal surgery for nasal polyps (NP) - - Worsening symptoms of chronic rhinosinusitis (CRS) requiring 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 - An endoscopic bilateral nasal polyp score (NPS) of at least 5 out of maximum score of 8 (with a minimum score of 2 in each nasal cavity) at screening and randomization - Ongoing symptoms (for at least 12 weeks before Visit 1) of: - - Nasal congestion/blockade/obstruction with moderate or severe (symptom severity score 2 or 3) at Visit 1 and a weekly average severity of greater than 1 in the week before randomization (Visit 2), AND - - At least one of the following two symptoms: loss of smell or rhinorrhea (anterior/posterior) - 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
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: - Participants with a history of clinically significant renal, hepatic, metabolic, neurologic, hematologic, ophthalmologic, respiratory (excluding those with asthma and aspirin-exacerbated respiratory disease [AERD] which may be included in the study), gastrointestinal, cardiovascular, cerebrovascular, or other significant medical illness or disorder, which, in the judgment of the Investigator, could interfere with the study or require treatment that might interfere with the study - Participants who are currently smoking tobacco and/or vaping, or participants in whom smoking/vaping cessation has occurred <6 months prior to Screening (Visit 1). Nicotine replacement therapy and/or noninhaled tobacco product use are not considered current smoking of tobacco - Participants meet any contraindications for mometasone furoate nasal spray (MFNS) such as hypersensitivity to MFNS or any of its components; or participants with uncontrolled opportunistic infections - Participants with a history of a severe systemic hypersensitivity reaction to a mAb - 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 etc) - Participants with severe uncontrolled asthma with history of 2 and/or more exacerbations, requiring SCS or 1 hospitalization requiring SCS in the past year - History of concomitant lung disease (other than asthma, eg, chronic obstructive pulmonary disease [COPD], interstitial lung disease) which in the opinion of the Investigator could interfere with performance and interpretation of spirometry - Participants treated with intranasal corticosteroid(s) (INCS) (MFNS is permitted), intranasal emitting devices/stents, nasal spray using exhalation delivery system such as Xhance during the screening period. In Japan and China INCS other than MFNS are permitted - Participants who have undergone any sinus intranasal surgery (including polypectomy) within 6 months before Visit 1 - Participants who received SCS 1 month prior to Screening (Visit 1) or during the screening period (between Visit 1 and Visit 2) - Known allergy to itepekimab or its excipients, or any drug or other allergy that, in the opinion of the Investigator, contraindicates participation in this study The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Change from baseline in the endoscopic NPS [Time Frame: Baseline to Week 24] The 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 from 0 to 4 with higher scores indicating larger polyps. The sum of right and left nostril scores ranges from 0 (no polyps) to 8 (large polyps). 2. Change from baseline in the nasal congestion score (NCS) [Time Frame: Baseline to Week 24] The NCS is scored using a 0-3 categorical scale where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms. Outcome value is defined as the preceding 28-day average of morning scores recorded in electronic diary (eDiary). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Change from baseline in endoscopic NPS [Time Frame: Baseline to Week 52] The 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 from 0 to 4 with higher scores indicating larger polyps. The sum of right and left nostril scores ranges from 0 (no polyps) to 8 (large polyps). 2. Change from baseline in NCS [Time Frame: Baseline to Week 52] The NCS is scored using a 0-3 categorical scale where 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms and 3 = severe symptoms. Outcome value is defined as the preceding 28-day average of morning scores recorded in eDiary. 3. Change from baseline in opacification of sinuses assessed by Computed Tomography (CT) scan using the Lund Mackay (LMK) score [Time Frame: Baseline to Week 24] The LMK system is based on localization with points given for degree of opacification: 0 = normal, 1 = partial opacification, 2 = total opacification. These points are then 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. The total score is the sum of scores from each side and ranges from 0 (normal) to 24 (total opacification). 4. Change from baseline in the Total Symptom Score (TSS) (nasal congestion/obstruction, anterior/posterior rhinorrhea, and loss of sense of smell) [Time Frame: Baseline to Weeks 24 and 52] The CRSwNP TSS is a composite score derived from nasal congestion/obstruction, anterior/posterior rhinorrhea, and loss of smell. The total score ranges from 0 to 9 with higher scores on TSS indicating greater overall symptom severity. 5. Change from baseline in loss of smell severity score using the daily CRSwNP sinonasal symptom eDiary, and University of Pennsylvania Smell Identification Test (UPSIT) score [Time Frame: Baseline to Weeks 24 and 52] The CRSwNP sinonasal symptom diary is designed to | — |
Countries
Canada, Chile, Japan, Republic of Korea, United Kingdom, United States
Contacts
Public ContactUnit Clinical
Sanofi K.K.
Outcome results
None listed