Itepekimab for COPD

(AERIFY-3 Trial)

Recruiting at 68 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

49 Participants Needed

Trial Summary

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.

What data supports the idea that Itepekimab for COPD is an effective drug?

The available research shows that Itepekimab, a drug targeting a protein called IL-33, has shown potential in treating COPD. In a study, it was tested on patients with moderate-to-severe COPD who were already on other inhaled therapies. While the study primarily focused on safety and genetic links, it suggests that Itepekimab could be effective due to its success in reducing inflammation in asthma, a related lung condition. Compared to other treatments like Mepolizumab, which is used for a specific type of COPD with high blood eosinophils, Itepekimab offers a new approach by targeting a different protein involved in lung inflammation. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Itepekimab for COPD?

Itepekimab, a drug targeting IL-33, has shown promise in reducing airway inflammation in asthma, which is similar to COPD. A study found that genetic factors related to IL-33 are linked to both asthma and COPD, suggesting potential benefits for COPD patients. ^{1 2 3 4 5}

What safety data is available for Itepekimab in COPD treatment?

The provided research does not contain specific safety data for Itepekimab in the treatment of COPD. The studies focus on immune checkpoint inhibitors and their adverse events in non-small cell lung cancer (NSCLC), which are not directly related to Itepekimab or COPD. ^{6 7 8 9 10}

Is the drug Itepekimab a promising treatment for COPD?

Itepekimab is a promising drug for COPD because it targets a protein called IL-33, which is linked to lung diseases like asthma and COPD. It has shown potential in reducing inflammation in the airways, which could help improve breathing in people with COPD. ^{1 2 3 11 12}

How does the drug itepekimab differ from other treatments for COPD?

Itepekimab is unique because it is a monoclonal antibody that targets interleukin-33 (IL-33), which is involved in airway inflammation. This approach is different from standard COPD treatments, which typically focus on bronchodilation or reducing inflammation through other pathways. ^{1 2 3 11 12}

What is the purpose of this trial?

This trial tests Itepekimab, a drug that blocks a protein to reduce lung inflammation, in smokers with COPD aged 40 to 70. The goal is to see if it helps improve their breathing and symptoms. Itepekimab has shown promise in reducing flare-ups and improving lung function in former smokers with COPD, with ongoing studies to confirm its effectiveness and safety.

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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 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]

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]

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]

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]

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]

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]

References

1. England 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. [2022]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Precision medicine in COPD: review of mepolizumab for eosinophilic COPD. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Current Controversies in the Pharmacological Treatment of Chronic Obstructive Pulmonary Disease. [2022]

6. Singapore 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. [2023]

7. Singapore 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. [2021]

8. China pubmed.ncbi.nlm.nih.gov

Radiomic biomarkers from chest computed tomography are assistive in immunotherapy response prediction for non-small cell lung cancer. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Adverse events of immunotherapy in non-small cell lung cancer: A systematic review and network meta-analysis. [2022]

10. England 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. [2020]

11. England 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. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Tezepelumab in the Treatment of Uncontrolled Severe Asthma. [2023]