Itepekimab for Sinusitis

(CEREN1 Trial)

Recruiting at 144 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Must be taking: Intranasal corticosteroids

Must not be taking: Systemic corticosteroids

Disqualifiers: Smoking, Severe asthma, Lung disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 10

Duration: 52 weeks

210 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called itepekimab for individuals with chronic sinusitis and nasal polyps. Researchers aim to evaluate the effectiveness and safety of itepekimab when combined with regular nose spray treatment. Participants will receive either a high dose, low dose, or a placebo (a treatment with no active medicine). The study seeks individuals who have experienced chronic sinusitis with nasal polyps for at least one year and have ongoing symptoms like nasal congestion or loss of smell. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the development of a potentially new treatment option.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you've used certain nasal sprays or systemic corticosteroids recently. It's best to discuss your specific medications 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 in several studies to assess its safety in humans. In one study, the rate of serious side effects leading to death was 1% for each group taking itepekimab, compared to 2% in the placebo group (a harmless pill with no active medicine). This suggests that serious side effects are relatively rare. Another study found that itepekimab improved asthma control and quality of life while reducing the number of blood eosinophils, which are white blood cells that can cause inflammation. These findings suggest that itepekimab is generally well-tolerated. However, like any treatment, side effects can still occur. Participants should discuss potential risks with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for sinusitis, which often involve antibiotics or corticosteroids, Itepekimab is unique because it targets the IL-33 cytokine pathway. This pathway plays a key role in the inflammatory process associated with sinusitis. By focusing on this specific mechanism, Itepekimab has the potential to more effectively reduce inflammation and improve symptoms over a 52-week period. Researchers are excited about Itepekimab because its subcutaneous administration, offered in both high and low doses, provides a targeted approach that could lead to better long-term management of sinusitis compared to traditional therapies.

What evidence suggests that this trial's treatments could be effective for chronic rhinosinusitis with nasal polyps?

Research has shown that itepekimab, a type of medication, may help treat chronic rhinosinusitis with nasal polyps (CRSwNP). In earlier studies, patients using itepekimab experienced fewer symptoms and smaller nasal polyps. The treatment was generally safe, with side effects similar to those in individuals taking a placebo. This trial will test various doses of itepekimab, both high and low, against a placebo to evaluate its effectiveness and safety in managing CRSwNP symptoms. ^{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?

Adults with chronic rhinosinusitis and nasal polyps who haven't found relief with standard treatments can join. They must be willing to add the trial medication to their usual nasal sprays for over a year, including follow-ups.

Inclusion Criteria

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.

I've had severe nasal blockage and either loss of smell or runny nose for over 12 weeks.

I have had chronic sinusitis with nasal polyps for at least a year.

Exclusion Criteria

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.

I have smoked or vaped within the last 6 months.

Participants with a history of a severe systemic hypersensitivity reaction to a mAb.

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 52 weeks as add-on therapy to intranasal corticosteroids

52 weeks

9 site visits, 20 phone/home visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

20 weeks

Not specified

What Are the Treatments Tested in This Trial?

Interventions

• Itepekimab

Trial Overview The study is testing Itepekimab's effectiveness in two different doses compared to a placebo, all alongside regular intranasal corticosteroids, over a period of one year in people with chronic sinus issues and nasal polyps.

How Is the Trial Designed?

Group I: Itepekimab low dose Experimental Treatment 3 Interventions

SC administration of Itepekimab low dose for 52 weeks

Group II: Itepekimab high dose Experimental Treatment 2 Interventions

Subcutaneous (SC) administration of Itepekimab high dose for 52 weeks

Group III: Placebo Placebo Group 2 Interventions

SC administration of matching placebo for 52 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

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 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]

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]

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]

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]

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]

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 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 (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.