Long‑Term Safety and Tolerability of Subcutaneous Itepekimab in Adults with Inadequately Controlled Chronic Rhinosinusitis with Nasal Polyps: Double‑Blind Extension Study

The primary objective is to assess the long‑term safety and tolerability of itepekimab in adults with inadequately controlled Chronic rhinosinusitis with nasal polyps who have completed prior studies. Secondary objectives include:

• Evaluation of the long‑term efficacy of itepekimab on nasal polyp size and nasal congestion symptoms.
• Characterization of the pharmacokinetic profile of itepekimab.
• Assessment of immunogenicity to itepekimab.
• Determination of the ability of itepekimab to reduce the risk of worsening or acute sinusitis requiring systemic corticosteroid therapy or sinus surgery.

The trial enrolled 234 participants diagnosed with chronic rhinosinusitis with nasal polyps who had completed a 52‑week intervention period in a prior Phase 3 itepekimab study (EFC18418 or EFC18419) and whose end‑of‑treatment visit occurred no later than five days before enrollment. Both male and female adults were included, encompassing the age groups defined by protocol codes 3 and 4 (adult and older adult ranges). All subjects were required to have inadequately controlled disease despite prior therapy, and enrollment was limited to individuals who were not pregnant or breastfeeding; women of childbearing potential had to agree to adhere to contraceptive guidance during the study and for at least 20 weeks after the last dose. The population also comprised vulnerable participants as defined by regulatory criteria. No additional lifestyle restrictions such as specific diet or physical‑activity requirements were stipulated.

The study is a double‑blind, placebo‑controlled extension trial evaluating the long‑term safety and tolerability of subcutaneous itepekimab in adult participants with inadequately controlled chronic rhinosinusitis with nasal polyps who have completed the 52‑week intervention of prior Phase 3 studies (EFC18418 or EFC18419). Participants are randomized in a 1:1 ratio to receive either itepekimab or a matched placebo administered by subcutaneous injection; both participants and investigators remain blinded to assignment throughout the study. The overall trial period spans from the projected recruitment start on 23 June 2026 to the anticipated study completion on 12 December 2028, with each enrolled subject remaining in the study for up to 24 months of follow‑up. After an initial screening visit confirming eligibility and completion of the previous study within five days, subjects undergo a baseline visit in which the first dose is administered. Subsequent study visits occur at regular intervals (e.g., every 12 weeks) for safety assessments, collection of adverse‑event data, endoscopic nasal polyp score (NPS) and nasal congestion score (NCS) measurements, serum itepekimab concentrations, and anti‑drug antibody testing. The primary endpoint is the incidence of treatment‑emergent adverse events, including serious adverse events and adverse events of special interest. Secondary endpoints include changes from baseline in NPS and NCS, functional drug concentrations, anti‑drug antibody incidence, and rates of systemic corticosteroid use or sinus surgery. The end‑of‑study visit concludes safety and efficacy evaluations and records any final outcomes. Early termination may occur if a participant experiences a serious adverse event, develops a condition that precludes continued subcutaneous dosing (e.g., pregnancy, significant infection), withdraws consent, or fails to comply with protocol‑required assessments.

The investigational product is itepekimab, supplied as a solution for injection in a pre‑filled syringe. The preparation is administered by subcutaneous injection at a dose of 0 mg per administration, consistent with the dosing regimen defined in the study protocol.

The comparator is a matched placebo that is identical in appearance to the active product and is provided as a solution for injection in a pre‑filled syringe. It is administered by the same route and schedule as the investigational product.

Both study arms receive the assigned injection at the frequency specified in the protocol, with dosing visits conducted at the study clinic. Compliance is monitored through documented administration records, returned syringes, and regular compliance checks performed by study staff.

Efficacy will be evaluated by comparing each participant's values to baseline measurements obtained in the parent studies (EFC18418, EFC18419). The primary efficacy parameters include the change from baseline in endoscopic nasal polyp score (NPS) and the change from baseline in nasal congestion score (NCS). Serum concentrations of itepekimab will be quantified to assess functional itepekimab concentration in serum, and the incidence of treatment‑emergent anti‑drug antibody (ADA) responses will be recorded. Clinical outcomes related to disease control will be captured by determining the proportion of participants requiring systemic corticosteroid therapy or sinus surgery and by calculating the annualized rate of systemic corticosteroid courses or surgeries for chronic rhinosinusitis.

All efficacy assessments will be performed using the validated instruments and laboratory assays employed in the parent trials. Endoscopic examinations will be used to derive NPS values, while NCS will be obtained through the established symptom scoring methodology. Serum itepekimab concentrations and ADA status will be measured with approved immunoassays. Data will be analyzed by comparing post‑baseline values to the original baseline, employing appropriate statistical methods for longitudinal change.