Itepekimab for Sinusitis

Not currently recruiting at 86 trial locations

Overseen By Trial Transparency email recommended (Toll free for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi

Must be taking: Mometasone furoate

Must not be taking: Intranasal corticosteroids

Disqualifiers: Nasal tumors, Fungal rhinosinusitis, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, itepekimab, to determine if it can improve symptoms in people with chronic sinus problems, specifically those without nasal polyps. The study compares two different doses of itepekimab to a placebo to assess its safety and effectiveness. Individuals with ongoing nasal congestion and sinus issues for at least 12 weeks, who have tried treatments like steroids, might be suitable for this trial. Participants will receive treatment for 24 weeks and attend a mix of in-person and remote visits. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial requires participants to stop using certain nasal sprays and corticosteroids before and during the study, except for a specific nasal spray provided by the study. If you're on other medications, the protocol doesn't specify, so it's best to discuss with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that itepekimab has been tested for safety in other conditions. One study found that people taking itepekimab experienced low rates of serious side effects, similar to those taking a placebo (a harmless pill with no active drug). Importantly, the number of deaths was about the same in both the itepekimab and placebo groups, suggesting it is relatively safe.

In studies on asthma, itepekimab improved patients' quality of life with few side effects. While these results are encouraging, the safety of itepekimab for sinusitis is still under investigation. The current trial is in an early stage, meaning the treatment is still being carefully evaluated for safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sinusitis?

Researchers are excited about Itepekimab for sinusitis because it represents a novel approach compared to existing treatments like nasal corticosteroids and antibiotics. Itepekimab is unique because it targets IL-33, a cytokine involved in inflammation, which is different from the typical focus on symptom relief seen in current options. This targeted approach aims to address the underlying cause of inflammation in sinusitis rather than just managing symptoms. Additionally, Itepekimab is administered subcutaneously, offering a distinct delivery method that might improve patient adherence and outcomes over time.

What evidence suggests that itepekimab might be an effective treatment for sinusitis?

Studies have shown that itepekimab may help reduce symptoms of sinusitis. Earlier research linked itepekimab, which targets a protein called IL-33 involved in immune responses, to symptom improvement in conditions with nasal inflammation. Early results suggest it could reduce inflammation, providing relief for people with sinus issues. While researchers are still gathering information about its use specifically for chronic rhinosinusitis without nasal polyps (CRSsNP), the mechanism of itepekimab appears promising for managing this condition. This trial will evaluate different doses of itepekimab, offering an interesting option for those seeking to address sinus problems. ^{2 4 6 7 8}

Who Is on the Research Team?

Clinical Sciences & Operations

Principal Investigator

Sanofi

Are You a Good Fit for This Trial?

This trial is for adults with chronic rhinosinusitis without nasal polyps, experiencing symptoms like nasal congestion for at least 12 weeks. They must have had prior sinus surgery, used systemic corticosteroids in the past two years, and show significant sinus inflammation on a CT scan. Women of childbearing potential must agree to effective contraception.

Inclusion Criteria

I've had nasal congestion for at least 12 weeks with a moderate to severe score.

Participants must have sinus Total Symptom Score (sTSS) ≥5 at Visit 1 and Visit 2

Participants must have at least one of the following features: Prior sinonasal surgery for chronic rhinosinusitis, Treatment with systemic corticosteroid(s) within the prior 2 years before Screening, Worsening symptoms of CRS in the past 2 years which would have required treatment with SCS, Participants must have bilateral inflammation of paranasal sinuses with bilateral ethmoid and maxillary opacification on screening CT scan, Participants must have a Sino-Nasal Outcome Test-22-Items (SNOT-22) score of ≥20 at Visit 1 and Visit 2, Participants who have received a stable dose of mometasone furoate nasal spray (MFNS) for at least 3 weeks before Visit 2, A female participant is eligible to participate if she is not pregnant or breastfeeding and meets contraceptive requirements

Exclusion Criteria

I have a tumor in my nasal cavity, it could be cancerous or not.

Known allergy to itepekimab or to its excipients

I do not have any serious health issues that could make this study unsafe for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive subcutaneous administration of Itepekimab or placebo for 24 weeks

24 weeks

7 site visits, 8 phone/remote visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

20 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Itepekimab

Trial Overview The study compares two dosing regimens of Itepekimab (an anti-IL-33 antibody) against a placebo over 24 weeks to assess its effectiveness and safety in treating chronic rhinosinusitis without nasal polyps. Participants will also use mometasone furoate nasal spray as part of their treatment.

How Is the Trial Designed?

Group I: Itepekimab low dose Experimental Treatment 3 Interventions

SC administration of Itepekimab low dose for 24 weeks

Group II: Itepekimab high dose Experimental Treatment 2 Interventions

Subcutaneous (SC) administration of Itepekimab high dose for 24 weeks

Group III: Placebo Placebo Group 2 Interventions

SC administration of matching placebo for 24 weeks

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

Itepekimab, a monoclonal antibody targeting interleukin-33, was found to be safe and well-tolerated in two phase I studies involving 63 participants, with no treatment-emergent anti-drug antibody responses detected.

The drug demonstrated effective pharmacokinetics with a long half-life and significant effects on reducing IL-33 levels and blood eosinophils, indicating its potential to reduce airway inflammation in asthma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of itepekimab in healthy adults and patients with asthma: Phase I first-in-human and first-in-patient trials. Kosloski, MP., Kalliolias, GD., Xu, CR., et al.[2022]

In a phase 2 trial involving 296 adults with moderate-to-severe asthma, itepekimab, a monoclonal antibody targeting interleukin-33, significantly reduced the incidence of asthma control loss compared to placebo, with 22% of patients experiencing loss of control versus 41% in the placebo group.

Itepekimab also improved lung function and quality of life, while showing a similar safety profile to other treatments, indicating its potential as an effective new therapy for asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma. Wechsler, ME., Ruddy, MK., Pavord, ID., et al.[2021]

Blocking IgE with omalizumab has been shown to provide rapid improvements in clinical symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), highlighting the importance of IgE-driven inflammatory pathways in this condition.

The review emphasizes the need for further research on diverse patient groups and biomarkers to enhance drug selection and to better understand the mechanisms of omalizumab in treating CRSwNP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Rhinosinusitis with Nasal Polyps: Targeting IgE with Anti-IgE Omalizumab Therapy. Kariyawasam, HH., James, LK.[2021]

In a 6-month randomized clinical trial involving subjects with chronic rhinosinusitis (CRS), treatment with the monoclonal antibody omalizumab led to reduced sinus inflammation on imaging, but the difference compared to placebo was not statistically significant.

Omalizumab treatment improved quality of life and symptoms as measured by the Sino-Nasal Outcome Test (SNOT-20) at multiple time points, while the placebo group showed no significant changes, suggesting a potential benefit of omalizumab in CRS management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis. Pinto, JM., Mehta, N., DiTineo, M., et al.[2022]

Omalizumab significantly improved various clinical outcomes in adults with chronic rhinosinusitis with nasal polyps (CRSwNP), including reductions in Nasal Polyps Score and Total Nasal Symptom Score, based on a systematic review of four randomized controlled trials involving 303 participants.

The treatment was found to be safe, with no significant difference in the risk of serious adverse events compared to placebo, indicating that omalizumab is well tolerated for managing CRSwNP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of omalizumab in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis of randomised controlled trials. Wu, Q., Yuan, L., Qiu, H., et al.[2021]

Omalizumab is an effective biological drug for treating allergic asthma, chronic spontaneous urticaria, and chronic rhinosinusitis with nasal polyps, showing good efficacy across these conditions.

Despite concerns about a potential increased cancer risk associated with omalizumab, extensive clinical studies and real-world data have consistently demonstrated its safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omalizumab and cancer risk: Current evidence in allergic asthma, chronic urticaria, and chronic rhinosinusitis with nasal polyps. Bagnasco, D., Canevari, RF., Del Giacco, S., et al.[2022]

IgE directly promotes eosinophil migration in chronic rhinosinusitis with nasal polyps (CRSwNP) by upregulating the CCR3 receptor, which is not observed in healthy individuals.

Omalizumab treatment effectively reduces eosinophil migration and local IgE levels in patients who respond to the therapy, with baseline local IgE counts being a strong predictor of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IgE directly affects eosinophil migration in chronic rhinosinusitis with nasal polyps through CCR3 and predicts the efficacy of omalizumab. Yu, J., Yan, B., Shen, S., et al.[2023]

In a study of 66 patients with chronic rhinosinusitis with nasal polyps (CRSwNP), dupilumab significantly reduced symptoms and nasal polyp scores after 6 and 12 months, indicating its effectiveness as a treatment.

The safety profile of dupilumab was favorable, with only 12.7% of patients experiencing injection site reactions and 11.1% having transient hypereosinophilia, suggesting it is a safe option for managing CRSwNP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety Profile of Dupilumab in Chronic Rhinosinusitis with Nasal Polyps: Real-Life Data in Tertiary Care. Galletti, C., Barbieri, MA., Ciodaro, F., et al.[2023]

Omalizumab (Xolair) shows consistent pharmacokinetics and pharmacodynamics in treating chronic rhinosinusitis with nasal polyps (CRSwNP), similar to its effects in allergic asthma, supporting its use in this condition.

In the phase 3 studies, a significant majority of patients (74.2% and 93.0%) achieved target serum free IgE levels after treatment, indicating that the dosing based on body weight and IgE levels is effective for CRSwNP patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and exposure-efficacy relationships of omalizumab in patients with nasal polyps. Zhu, R., Owen, R., Wilkins, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06691113

NCT06691113 | A Proof-of-Concept Study to Assess the ... The purpose of the study is to evaluate the efficacy, safety and tolerability of 2 dosing regimens of itepekimab compared to placebo in male and female ...

2. sanofistudies.com sanofistudies.com/cwout/CW-V9DEXS//ca/en/listing/313004/a-proof-of-concept-study-to-2/

A Proof-of-Concept Study to Assess the Efficacy, Safety The purpose of the study is to evaluate the efficacy, safety and tolerability of 2 dosing regimens of itepekimab compared to placebo in male and female ...

3. sanofi.com sanofi.com/en/media-room/press-releases/2025/2025-05-30-05-00-00-3090818

Press Release: Itepekimab met the primary endpoint in one ... In AERIFY-1, the overall rates of AEs were 67% and 68% for itepekimab every two weeks and every four weeks, respectively, compared to 68% for ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11365161/

Exploratory pharmacodynamics and efficacy of PF ... Rhinosinusitis symptoms were improved, and nasal polyps were decreased in size following treatment with PF-06817024 in patients with CRSwNP. In ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06691113/a-proof-of-concept-study-to-assess-the-efficacy-safety-and-tolerability-of-itepekimab-anti-il-33-mab-in-participants-with-chronic-rhinosinusitis-without-nasal-polyps

IL-33 mAb) in Participants With Chronic Rhinosinusitis ... The purpose of the study is to evaluate the efficacy, safety and tolerability of 2 dosing regimens of itepekimab compared to placebo in male and female ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06834347

NCT06834347 | A Phase 3 Study to Assess the Efficacy, ... 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 ...

7. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/itepekimab-met-primary-endpoint-one-two-chronic-obstructive

Itepekimab Met Primary Endpoint in One of Two Chronic ... AEs leading to death were 1% for each itepekimab arm compared to 2% for placebo in AERIFY-1, and 3% for each itepekimab arm compared to 2% for ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2024257

Efficacy and Safety of Itepekimab in Patients with Moderate ... Itepekimab treatment improved asthma control and quality of life, as compared with placebo, and led to a greater reduction in the mean blood eosinophil count.