A Phase 3 Study to Assess the Efficacy, Safety, and Tolerability of Itepekimab (Anti-IL-33 mAb) in Adult Japanese Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps

Official title

A Randomized, Double-blind, Parallel-group, 52-week Trial to Investigate the Efficacy, Safety, and Tolerability of Itepekimab in Adult Japanese Participants With Inadequately-controlled Chronic Rhinosinusitis With Nasal Polyps

Overview

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

• Drug Itepekimab (SAR440340)
  Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous
• Drug Placebo
  Pharmaceutical form: Solution for injection in prefilled syringe. Route of administration: Subcutaneous

Primary outcome measures

• Change from baseline in the endoscopic NPS [Time frame: Baseline to Week 24]

Secondary outcome measures (9)

• Change from baseline in the NCS [Time frame: Baseline to Week 24]
• Proportion of NPS responders (defined as participants with improvement by at least 1 points in NPS) [Time frame: Week 24 and Week 52]
• Change from baseline in endoscopic NPS [Time frame: Baseline to Week 52]
• Change from baseline in NCS [Time frame: Baseline to Week 52]
• Change from baseline in the TSS (nasal congestion/obstruction, anterior/posterior rhinorrhea, and loss of sense of smell) [Time frame: Baseline to Weeks 24 and 52]
• Change from baseline in loss of smell severity score using the daily CRSwNP sinonasal symptom eDiary [Time frame: Baseline to Weeks 24 and 52]
• Incidence of TEAEs, TESAEs, TEAESIs and TEAEs leading to treatment discontinuation [Time frame: Baseline to End of Study (EOS) (Week 72)]
• Itepekimab concentration in serum [Time frame: Baseline to EOS (Week 72)]
• Incidence of treatment-emergent antidrug antibody (ADA) responses [Time frame: Baseline to EOS (Week 72)]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07484230 · EFC21029 · U1111-1322-6073

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗