Itepekimab for Sinusitis (CEREN1 Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Sanofi
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?EFC18418 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.
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.
What evidence supports the effectiveness of the drug Itepekimab for treating sinusitis?
Itepekimab, a drug that targets a protein called interleukin-33, has shown promise in reducing inflammation in asthma patients, which suggests it might help with sinusitis too, as both conditions involve inflammation. However, direct evidence for its effectiveness in sinusitis is not available yet.
12345Is itepekimab safe for humans?
Itepekimab has been tested in healthy adults and patients with asthma, and it was well-tolerated with no significant safety concerns reported in these studies.
13678How does the drug itepekimab differ from other treatments for sinusitis?
Itepekimab is unique because it is a monoclonal antibody that targets interleukin-33, a protein involved in inflammation, which is different from other treatments like omalizumab that target IgE. This approach may offer a new way to reduce inflammation in sinusitis.
12359Eligibility Criteria
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
I am 18 years old or older.
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
I am not allergic to mometasone furoate nasal spray and do not have any uncontrolled infections.
I have severe asthma with recent serious flare-ups or a hospital stay.
I have not had sinus or nasal surgery in the last 6 months.
I have a tumor in my nasal cavity, it could be cancerous or non-cancerous.
Participant Groups
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.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Itepekimab low doseExperimental Treatment3 Interventions
SC administration of Itepekimab low dose for 52 weeks
Group II: Itepekimab high doseExperimental Treatment2 Interventions
Subcutaneous (SC) administration of Itepekimab high dose for 52 weeks
Group III: PlaceboPlacebo Group2 Interventions
SC administration of matching placebo for 52 weeks
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Newport Native MD- Site Number : 8400031Newport Beach, CA
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Who is running the clinical trial?
SanofiLead Sponsor
Regeneron PharmaceuticalsIndustry Sponsor
References
Pharmacokinetics and pharmacodynamics of itepekimab in healthy adults and patients with asthma: Phase I first-in-human and first-in-patient trials. [2022]Itepekimab is a monoclonal antibody that targets interleukin (IL-33) and has been shown to reduce airway inflammation and associated tissue damage in preclinical studies. We assessed the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamic profiles of single-ascending and multiple-ascending doses of itepekimab in two randomized, double-blind, placebo-controlled phase I studies. Healthy adults (N = 40) were randomized to the single-dose study and patients with moderate asthma (N = 23) to the multiple-dose study. Itepekimab was administered intravenously (0.3, 1, 3, or 10 mg/kg infusion) or subcutaneously (150 mg) in the single-dose study and subcutaneously (75 or 150 mg weekly for 4 weeks) in the multiple-dose study. Itepekimab exhibited linear PKs across studies and dose-proportional increases in mean maximum concentration in serum and area under the concentration-time curve following single intravenous or multiple subcutaneous doses. Itepekimab demonstrated mean subcutaneous bioavailability of 59-73% and a long terminal half-life (30.0-31.6 days). IL-33 concentrations in most healthy participants and patients with asthma were undetectable at baseline. Following administration of itepekimab in both studies, total IL-33 concentrations increased and blood eosinophils decreased, both with durable effect. Itepekimab was well-tolerated in both studies with no detection of treatment-emergent anti-drug antibody responses.
Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma. [2021]Monoclonal antibodies targeting IgE, interleukin-4 and -13, and interleukin-5 are effective in treating severe type 2 asthma, but new targets are needed. Itepekimab is a new monoclonal antibody against the upstream alarmin interleukin-33. The efficacy and safety of itepekimab as monotherapy, as well as in combination with dupilumab, in patients with asthma are unclear.
Efficacy and safety of omalizumab in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis of randomised controlled trials. [2021]To assess the efficacy and safety of omalizumab for chronic rhinosinusitis with nasal polyps (CRSwNP) and to identify evidence gaps that will guide future research on omalizumab for CRSwNP.
A randomized, double-blind, placebo-controlled trial of anti-IgE for chronic rhinosinusitis. [2022]Evidence suggests IgE may play a role in chronic rhinosinusitis (CRS). We sought to determine if treatment with a monoclonal antibody against IgE (omalizumab) is effective in reducing CRS inflammation. We performed a randomized, double blind, placebo controlled clinical trial in subjects with CRS despite treatment (including surgery). Subjects were randomized to receive omalizumab or placebo for 6 months. The primary outcome was quantitative measurement of sinus inflammation on imaging. Secondary outcome measures included quality of life, symptoms, and cellular inflammation, nasal airflow (NPIF) and olfactory testing (UPSIT). Subjects on omalizumab showed reduced inflammation on imaging after treatment, whereas those on placebo showed no change. The net difference, however, was not different between treatments. Treatment with omalizumab was associated with improvement in the Sino-Nasal Outcome Test (SNOT-20) at 3, 5, and 6 months compared to baseline with no significant changes in the control group. Remaining measures showed no significant differences across treatments. We conclude that IgE plays, at most, a small role in the mucosal inflammation of CRS and the symptoms. Placebo controlled, blinded studies with larger enrollment are needed to determine the clinical significance of any potential change.
Chronic Rhinosinusitis with Nasal Polyps: Targeting IgE with Anti-IgE Omalizumab Therapy. [2021]Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex, clinically heterogeneous and persistent inflammatory disorder of the upper airway. Detailed mechanistic insights into disease pathogenesis are lacking, but it is now accepted that local tissue IgE driven T2-high inflammatory pathways are critical to disease. The recent CRSwNP Phase 3 POLYP1 and POLYP2 replicate studies of blocking IgE with omalizumab confirmed rapid improvements in all clinical parameters of sinonasal disease, confirming a pivotal role for IgE driven inflammatory pathways in CRSwNP. This review summarises the biology of IgE in relation to CRSwNP. Insight into how IgE may drive CRSwNP is evaluated in the context of clinical improvements seen with omalizumab. The need for further studies using a broader patient and biomarker specific groups to aid more precise drug-patient selection alongside more detailed mechanistic studies of omalizumab in CRSwNP is highlighted.
Effectiveness and Safety Profile of Dupilumab in Chronic Rhinosinusitis with Nasal Polyps: Real-Life Data in Tertiary Care. [2023]Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a type 2 pattern of inflammation resulting in the production of some cytokines. Dupilumab radically changes the treatment of CRSwNP, but, considering its recent approval, it may be useful to evaluate its safety profile in a real-world setting. This work aimed to prospectively highlight the effectiveness and safety profile of dupilumab in patients with CRSwNP enrolled in the Otorhinolaryngology Unit of the University Hospital of Messina. An observational cohort study was carried out considering all patients treated with dupilumab. A descriptive analysis was conducted reporting all demographic characteristics, endoscopic evaluations, and symptom conditions. A total of 66 patients were treated with dupilumab, but three patients were excluded due to a lack of adherence during the observational period. A statistically significant reduction in the Sino-Nasal Outcome Test 22 (SNOT-22) and nasal polyps score (NPS) was shown at the 6th and 12th months compared to baseline values (SNOT-22, -37 and -50, p < 0.001 for both comparisons; NPS, -3 and -4, p < 0.001 for both comparisons). During the follow-up, eight patients (12.7%) had a reaction at the site of injection, and seven (11.1%) had transient hypereosinophilia. Given the optimal treatment response and the minimal adverse effects observed, clinicians should consider dupilumab a safe and effective treatment. Further studies are necessary to better understand the long-term effects.
Omalizumab and cancer risk: Current evidence in allergic asthma, chronic urticaria, and chronic rhinosinusitis with nasal polyps. [2022]Omalizumab is a biological drug targeting circulating IgE, approved for use in allergic asthma, chronic spontaneous urticaria, and recently for chronic rhinosinusitis with nasal polyps, with good efficacy in all these settings. Some concerns about omalizumab safety have been raised as its use has been recently linked to potential increased cancer risk. Nevertheless, literature evidence does not support this statement, and clinical studies and evidence from real-world registries and surveillance analysis have consistently reported drug safety.
Pharmacokinetics and exposure-efficacy relationships of omalizumab in patients with nasal polyps. [2022]The anti-immunoglobulin E (IgE) antibody, omalizumab (Xolair), is approved in the United States for the treatment of allergic asthma and chronic spontaneous urticaria, and has recently been studied for the treatment of nasal polyposis following completion of the two replicate phase 3 studies (POLYP 1 and POLYP 2). The dosing of omalizumab used in the phase 3 studies is based on a combination of patients' pre-treatment IgE level and body weight, similar to the approach used in allergic asthma. The objectives of the current analyses were to evaluate whether the pharmacokinetics (PK) of omalizumab and its pharmacodynamic (PD) effect on free and total IgE level in chronic rhinosinusitis with nasal polyps (CRSwNP) are consistent with those in allergic asthma via population PK/PD modeling and simulation, and to graphically explore exposure-response relationships and free IgE-response relationships in CRSwNP. Omalizumab PK and PD effect of total and free IgE in CRSwNP are generally consistent with those in asthma. Observed post-treatment free IgE suppressions were generally within the target range of the baseline IgE- and body weight-based omalizumab dosing table, with 74.2% and 93.0% of patients achieving a serum free IgE level below 25 ng/mL and 50 ng/mL, respectively at Week 24. Exposure-response analyses indicated that there was no clear correlation between omalizumab or free IgE concentration and key efficacy endpoints within the POLYP studies. Overall, these results indicate that the body weight and IgE-based dosing regimen of omalizumab was appropriate for use in CRSwNP patients.
IgE directly affects eosinophil migration in chronic rhinosinusitis with nasal polyps through CCR3 and predicts the efficacy of omalizumab. [2023]Whether IgE affects eosinophil migration in chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unclear. Moreover, our understanding of local IgE, eosinophils, and omalizumab efficacy in CRSwNP remains limited.