Chronic Rhinosinusitis With Nasal Polyps
Conditions
Brief summary
This is a randomized, multicenter, double-blind, Phase 3 study with 2 parallel groups. The purpose of this study is to evaluate the efficacy, safety, and tolerability of 2 different dosing regimens of itepekimab monotherapy in Japanese participants aged 18 years or older with chronic rhinosinusitis with nasal polyp(s) (CRSwNP) who are not adequately controlled despite previous surgery and/or treatment with systemic corticosteroid(s) (SCS). The total study duration par participant is approximately 76 week, including: * A screening period for up to 4 weeks. * A randomized study intervention period for up to 52 weeks * A post-intervention safety follow-up for up to 20 weeks * The number of visits will be 9 site visits and 20 phone/home visits
Interventions
Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous
DRUGPlacebo
Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous
Sponsors
Sanofi
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must be 18 years of age or older. * Participants with a history of CRSwNP for at least 1 year. * Participants must have at least one of the following features: * Prior sinonasal surgery for NP. * Worsening symptoms of CRS requiring treatment with SCS within the prior 1 year. * An endoscopic bilateral NPS of at least 5 out of maximum score of 8 (with a minimum score of 2 in each nasal cavity). * Ongoing symptoms (for at least 12 weeks before Visit 1) of: * Nasal congestion/blockade/obstruction with moderate or severe symptom (score of 2 or 3), AND * At least one of the following two symptoms: loss of smell or rhinorrhea (anterior/posterior). * Not currently on and have not been receiving INCS for at least one month. * 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 a history of clinically significant renal, hepatic, metabolic, neurologic, hematologic, ophthalmologic, respiratory (excluding those with asthma and 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. Nicotine replacement therapy and/or noninhaled tobacco product use are not considered current smoking of tobacco. * Participants with a history of a severe systemic hypersensitivity reaction to a mAb. * Participants with conditions/concomitant diseases making them non-evaluable 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. * Participants treated with intranasal corticosteroid(s) (INCS), intranasal emitting devices/stents, nasal spray using exhalation delivery system such as XhanceTM one month prior during the screening period. * 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 | Description |
|---|---|---|
| Change from baseline in the endoscopic NPS | Baseline to Week 24 | The Nasal Polyp Score (NPS) is the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. Nasal polyp 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the NCS | Baseline to Week 24 | The Nasal Congestion Score (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. |
| Proportion of NPS responders (defined as participants with improvement by at least 1 points in NPS) | Week 24 and Week 52 | — |
| Change from baseline in endoscopic NPS | Baseline to Week 52 | The NPS is the sum of the right and left nostril scores, as evaluated by means of nasal endoscopy. Nasal polyp 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). |
| Change from baseline in NCS | 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. |
| Change from baseline in the TSS (nasal congestion/obstruction, anterior/posterior rhinorrhea, and loss of sense of smell) | Baseline to Weeks 24 and 52 | The CRSwNP Total Symptom Score (TSS) is a composite score derived from nasal congestion (NC)/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. |
| Change from baseline in loss of smell severity score using the daily CRSwNP sinonasal symptom eDiary | Baseline to Weeks 24 and 52 | The CRSwNP sinonasal symptom diary is designed to assess the severity of chronic rhinosinusitis (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. |
| Incidence of TEAEs, TESAEs, TEAESIs and TEAEs leading to treatment discontinuation | Baseline to End of Study (EOS) (Week 72) | Treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment-emergent adverse events of special interest (TEAESIs) |
| Itepekimab concentration in serum | Baseline to EOS (Week 72) | — |
| Incidence of treatment-emergent antidrug antibody (ADA) responses | Baseline to EOS (Week 72) | — |
Contacts
CONTACTTrial Transparency email recommended (Toll free for US & Canada)
STUDY_DIRECTORClinical Sciences & Operations
Sanofi
Outcome results
None listed