NCT06834360Active, not recruitingPhase 3
A Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Phase 3 Trial to Investigate the Efficacy, Safety, and Tolerability of Itepekimab in Adult Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- Sanofi
- Enrollment
- 216
- Locations
- 213
- Primary Endpoint
- Change from baseline in the endoscopic NPS
Study Overview
Brief Summary
EFC18419 is a multinational, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 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 as add-on therapy to intranasal corticosteroids (INCS) in male and female participants with chronic rhinosinusitis with nasal polyps (CRSwNP) aged 18 years of age and older.
Study details include:
- The study duration per participant (4-week screening, 52-week treatment, 20-week safety follow-up) will be up to 76 weeks. For participants transitioning to the LTS18420 study, the study duration will be 56 weeks.
- The treatment duration will be up to 52 weeks.
- The number of visits will be 9 site visits and 20 phone/home visits.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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 1 year before screening (Visit 1).
- •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
- •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, 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 XhanceTM 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
- •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.
Arms & Interventions
Itepekimab low dose
Experimental
SC administration of Itepekimab low dose for 52 weeks
Intervention: Itepekimab (SAR440340) (Drug)
Itepekimab low dose
Experimental
SC administration of Itepekimab low dose for 52 weeks
Intervention: Placebo (Drug)
Placebo
Placebo Comparator
SC administration of matching placebo for 52 weeks
Intervention: Placebo (Drug)
Itepekimab low dose
Experimental
SC administration of Itepekimab low dose for 52 weeks
Intervention: Mometasone furoate nasal spray (MFNS) (Drug)
Itepekimab high dose
Experimental
Subcutaneous (SC) administration of Itepekimab high dose for 52 weeks
Intervention: Mometasone furoate nasal spray (MFNS) (Drug)
Placebo
Placebo Comparator
SC administration of matching placebo for 52 weeks
Intervention: Mometasone furoate nasal spray (MFNS) (Drug)
Itepekimab high dose
Experimental
Subcutaneous (SC) administration of Itepekimab high dose for 52 weeks
Intervention: Itepekimab (SAR440340) (Drug)
Outcomes
Primary Outcomes
Change from baseline in the endoscopic NPS
Time Frame: 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).
Change from baseline in the NCS
Time Frame: 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.
Secondary Outcomes
- Change from baseline in endoscopic NPS(Baseline to Week 52)
- Change from baseline in NCS(Baseline to Week 52)
- Change from baseline in SNOT-22 total score(Baseline to Weeks 24 and 52)
- Proportion of participants with CRSwNP requiring systemic corticosteroid(s) (SCS) or surgery for CRS(Baseline up to Week 52)
- Annualized rate of SCS course or surgery for CRS(Baseline up to Week 52)
- Change from baseline in opacification of sinuses assessed by Computed Tomography (CT) scan using the LMK score(Baseline to Week 24)
- Change from baseline in the TSS (nasal congestion/obstruction, anterior/posterior rhinorrhea, and loss of sense of smell)(Baseline to Weeks 24 and 52)
- Change from baseline in loss of smell severity score using the daily CRSwNP sinonasal symptom eDiary, and UPSIT score(Baseline to Weeks 24 and 52)
- Change from baseline in pre-BD FEV1 (in mL) in participants with co-morbid asthma(Baseline to Weeks 24 and 52)
- Change from baseline in PROMIS SD-SF-8b scores(Baseline to Weeks 24 and 52)
- Time to first either SCS or surgery for CRS(Baseline through Week 52)
- Change from baseline in ACQ-5 score in participants with co-morbid asthma(Baseline to Weeks 24 and 52)
- Change from the baseline in NPS and NCS in the subgroup of patients with aspirin-exacerbated respiratory disease (AERD)(Baseline to Weeks 24 and 52)
- Proportion of participants with AERD requiring SCS or surgery for CRS(Baseline up to Week 52)
- Annualized rate of SCS course or surgery for CRS in participants with AERD(Baseline up to Week 52)
- Time to first either SCS or surgery for CRS in participants with AERD(Baseline through Week 52)
- Change from baseline in pre-BD FEV1 (in ml) in participants with AERD(Baseline to Weeks 24 and 52)
- Proportion of NPS responders (defined as participants with improvement by at least 1 point in NPS)(Weeks 24 and 52)
- Proportion of NPS responders (defined as participants with improvement by at least 2 points in NPS)(Weeks 24 and 52)
- Incidence of treatment-emergent adverse Events (TEAEs), treatment-emergent serious adverse events (TESAEs), treatment-emergent adverse events of special interest (TEAESIs) and TEAEs leading to treatment discontinuation(Baseline to End of Study (EOS) (Week 72))
- Itepekimab concentration in serum(Baseline to EOS (Week 72))
- Incidence of treatment-emergent anti-itepekimab antibody (ADA) responses(Baseline to EOS (Week 72))
Investigators
Study Sites (213)
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