Itepekimab for COPD

(AERIFY-3 Trial)

No longer recruiting at 69 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi

Must be taking: Controller therapy

Must not be taking: Immunosuppressive therapy

Disqualifiers: Asthma, Pulmonary disease, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 11

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Itepekimab to assess its effects on lung inflammation in people with COPD, a lung disease that makes breathing difficult. The study consists of two parts: one for former smokers and one for current smokers. Participants will continue their usual COPD medications while receiving Itepekimab, administered as an injection every two weeks for 12 weeks. The trial seeks individuals who have had COPD for at least a year, have a history of smoking at least 10 pack-years, and experience chronic cough or breathing problems. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

No, you can continue taking your current COPD controller medications during the trial. However, you cannot use systemic corticosteroids or antibiotics for acute exacerbations of COPD during the study.

Will I have to stop taking my current medications?

You can continue taking your current COPD controller medications during the study, but you may need to stop using systemic corticosteroids and antibiotics if they are for acute COPD flare-ups.

Is there any evidence suggesting that Itepekimab is likely to be safe for humans?

Research shows that itepekimab has been tested for safety in people with COPD. Studies have found that it helped reduce flare-ups and improved lung function in former smokers. Participants generally tolerated the treatment well in these studies. Some research is still ongoing to confirm its safety and effectiveness. Overall, the data suggest that itepekimab is safe for humans, with no major safety concerns reported so far. ^{1 2 3 4 5}

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

Itepekimab is unique because it targets a specific protein called IL-33, which plays a role in inflammation associated with COPD. Unlike standard treatments such as bronchodilators and corticosteroids, which primarily focus on opening airways or reducing inflammation broadly, Itepekimab works by blocking the IL-33 pathway, potentially offering a more targeted approach to managing the disease. Researchers are excited about Itepekimab because it could provide relief for both former and current smokers with COPD, offering a new hope for those who might not respond well to existing therapies.

What evidence suggests that Itepekimab might be an effective treatment for COPD?

Research has shown that Itepekimab, administered to participants in this trial, can benefit individuals with COPD (chronic obstructive pulmonary disease) who have a history of smoking. Studies indicate that it reduced the number of COPD flare-ups in former smokers and improved their lung function. Additionally, Itepekimab extended the time before the next COPD flare-up for many of these individuals. However, results varied in other studies, showing effectiveness for some but not all. Overall, Itepekimab appears promising, particularly for those who have quit smoking. ^{1 3 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 former and current smokers aged 40-70 with COPD, diagnosed per GOLD standards. They must have a BMI ≥18 kg/m2, be vaccinated against SARS-CoV-2, not pregnant or breastfeeding (if female), and agree to contraception if of childbearing potential. Participants should have used standard COPD treatments for at least 3 months and had an exacerbation treated with steroids in the past 5 years.

Inclusion Criteria

I quit smoking more than 6 months ago and don't plan to start again.

You have smoked an average of one pack of cigarettes a day for at least 10 years.

If you are a current smoker, you cannot participate in the study if you are not currently in a program to quit smoking or do not plan to start one during the screening period.

Exclusion Criteria

I need more than 2 liters per minute of oxygen for daily use.

If you used to smoke, you cannot have smoked or vaped anything in the last 6 months.

I have had a serious COPD flare-up in the last 8 weeks.

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 every 2 weeks for 12 weeks

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

20 weeks

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Itepekimab

Trial Overview The study tests Itepekimab's effect on airway inflammation in COPD patients over a total of approximately 36 weeks: a four-week screening period, twelve-week treatment period, followed by twenty weeks of follow-up while maintaining their usual COPD medications.

How Is the Trial Designed?

Group I: Itepekimab Experimental Treatment 1 Intervention

This arm includes participants from 2 populations: Part A-former smokers and Part B-current smokers. Subcutaneous (SC) administration of Itepekimab every 2 weeks (Q2W) for 12 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 study of 72 treatment-naïve patients with advanced non-small cell lung cancer (NSCLC) and high PD-L1 expression, pembrolizumab showed an objective response rate of 45.8%, with even higher rates of 70.0% in patients with pre-existing interstitial lung disease (ILD).

Patients with ILD had similar overall survival rates compared to those without ILD, suggesting that pembrolizumab can be safely administered to NSCLC patients with ILD without compromising their prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing interstitial lung disease does not affect prognosis in non-small cell lung cancer patients with PD-L1 expression ≥50% on first-line pembrolizumab. Yamaguchi, O., Kaira, K., Shinomiya, S., et al.[2021]

In a meta-analysis of 16 clinical trials involving 6208 patients with non-small cell lung cancer, the overall incidence of immune-related adverse events (irAEs) was found to be 22%, with a higher rate of severe irAEs (4%) associated with PD-1 inhibitors compared to PD-L1 inhibitors.

The most common organ-specific irAEs occurred in the endocrine system, skin, pulmonary tract, and gastrointestinal tract, with pneumonitis being the leading cause of death among the 14 patients (0.34%) who died due to irAEs, highlighting the importance of monitoring and managing these side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events associated with programmed cell death protein-1 and programmed cell death ligand 1 inhibitors for non-small cell lung cancer: a PRISMA systematic review and meta-analysis. Sun, X., Roudi, R., Dai, T., et al.[2020]

A study involving 132 patients with non-small cell lung cancer developed prediction models using radiomic and clinical features to identify those likely to benefit from anti-PD-1/PD-L1 therapy, achieving a high prediction accuracy with an AUC-ROC of 87%.

The radiomic model effectively predicted progression-free survival, indicating that imaging features can help select patients who may respond well to immunotherapy, potentially reducing the risk of unnecessary treatment and associated immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiomic biomarkers from chest computed tomography are assistive in immunotherapy response prediction for non-small cell lung cancer. Schroeder, KE., Acharya, L., Mani, H., et al.[2023]

Mepolizumab has been shown to significantly reduce the rate of exacerbations in patients with severe COPD who frequently experience flare-ups and have elevated blood eosinophil levels.

This treatment represents a step forward in precision medicine for COPD, allowing for more targeted therapies based on individual patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision medicine in COPD: review of mepolizumab for eosinophilic COPD. Long, G., Wall, J.[2020]

In clinical trials, subcutaneous tezepelumab significantly reduced the annualized asthma exacerbation rate by up to 71% compared to placebo, demonstrating its efficacy in treating severe uncontrolled asthma.

Tezepelumab is effective across various asthma phenotypes, including nonallergic and noneosinophilic types, making it a versatile treatment option for patients with severe asthma regardless of their specific characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab in the Treatment of Uncontrolled Severe Asthma. Feist, J., Lipari, M., Kale-Pradhan, P.[2023]

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]

In a study of 260 patients with advanced or recurrent non-small cell lung cancer (NSCLC), a tumor proportion score (TPS) of 90% or higher and adenocarcinoma histology were identified as independent risk factors for immune-related adverse events (irAEs) during first-line treatment.

While patients with TPS ≥ 90% showed better response rates in later-line treatments, there were no significant differences in overall survival between groups, indicating that high TPS may require careful monitoring for irAEs without affecting long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-small cell lung cancer with tumor proportion score > 90% could increase the risk of severe immune-related adverse events in first-line treatments with immune checkpoint inhibitors: A retrospective single-center study. Akazawa, Y., Yoshikawa, A., Kanazu, M., et al.[2023]

In a phase 2a trial involving 343 patients with moderate-to-severe COPD, itepekimab did not significantly reduce the overall rate of acute exacerbations compared to placebo, but showed promising results in former smokers, with a 42% reduction in exacerbation rates and improved lung function.

Genetic analyses indicated that certain IL-33 pathway variants are associated with COPD risk, suggesting a potential mechanism for how itepekimab may work, particularly in patients with specific genetic backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of itepekimab in patients with moderate-to-severe COPD: a genetic association study and randomised, double-blind, phase 2a trial. Rabe, KF., Celli, BR., Wechsler, ME., et al.[2022]

Tezepelumab, a monoclonal antibody targeting thymic stromal lymphopoietin, significantly reduced asthma exacerbations by up to 71% in adults with severe, uncontrolled asthma, as shown in the previous PATHWAY phase 2b study.

The ongoing NAVIGATOR phase 3 study, involving 1061 participants, aims to evaluate tezepelumab's efficacy in reducing exacerbations and improving lung function and quality of life across various asthma phenotypes, including those with low eosinophil counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Menzies-Gow, A., Colice, G., Griffiths, JM., et al.[2021]

The shift towards precision medicine in COPD emphasizes the need to integrate both biological and clinical information, using biomarkers to identify patient endotypes for more personalized treatment decisions.

Recent clinical trials suggest that monitoring the trajectory of FEV1 changes, rather than relying solely on a single FEV1 measurement, is crucial for assessing disease activity and guiding pharmacotherapy in COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Controversies in the Pharmacological Treatment of Chronic Obstructive Pulmonary Disease. Singh, D., Roche, N., Halpin, D., et al.[2022]

In a review of 52 randomized controlled trials involving 23,322 patients with non-small cell lung cancer (NSCLC), the incidence of serious adverse events (AEs) was found to be similar between immune monotherapy and chemotherapy, with serious AEs occurring in about 33-48% of patients depending on the treatment type.

Certain immune-related adverse events (irAEs), such as colitis, pneumonitis, and rash, were more common in immunotherapy groups compared to chemotherapy, and interestingly, the occurrence of serious AEs like hepatitis and pneumonitis was positively correlated with better progression-free survival in patients receiving PD1 and PDL1 therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of immunotherapy in non-small cell lung cancer: A systematic review and network meta-analysis. Zhou, C., Li, M., Wang, Z., et al.[2022]

Citations

1. 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 ... Itepekimab met the primary endpoint in one of two COPD phase 3 studies. AERIFY-1 study met its primary endpoint of a statistically ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34302758/

Safety and efficacy of itepekimab in patients with moderate- ... Itepekimab reduced exacerbation rate and improved lung function in former smokers with COPD. Two phase 3 clinical studies are ongoing to confirm the efficacy ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04751487

NCT04751487 | Study to Assess the Efficacy, Safety, and ... Evaluate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate-or-severe COPD exacerbations in former smokers with moderate- ...

4. ajmc.com ajmc.com/view/itepekimab-shows-mixed-results-in-phase-3-copd-trials

Itepekimab Shows Mixed Results in Phase 3 COPD Trials Itepekimab, an investigational monoclonal antibody for chronic obstructive pulmonary disease (COPD), demonstrated mixed results in a pair of ...

5. publications.ersnet.org publications.ersnet.org/content/erj/64/suppl68/oa3645

Reduction in exacerbations with itepekimab in former smokers ... Itepekimab significantly increased time to ECOPD and reduced the frequency of ECOPD in former smokers, irrespective of exacerbation history.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04701983

NCT04701983 | Study to Assess the Efficacy, Safety, and ... Study to Assess the Efficacy, Safety, and Tolerability of SAR440340/​REGN3500/​Itepekimab in Chronic Obstructive Pulmonary Disease (COPD) (AERIFY-1).

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11417606/

AERIFY-1/2: two phase 3, randomised, controlled trials of ... Additional end-points in the study will focus on patient-reported outcomes including symptom control and safety and tolerability of itepekimab treatment. The ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2213260021001673

Safety and efficacy of itepekimab in patients with moderate ... The primary endpoint in the overall population was not met, subgroup analysis showed that itepekimab reduced exacerbation rate and improved lung function in ...