Itepekimab for COPD

(AERIFY-1 Trial)

No longer recruiting at 565 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi

Must be taking: Inhaled corticosteroids, Long-acting beta-agonists

Disqualifiers: Asthma, Active smoking, Heart 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: Unknown

Duration: 24 to 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called itepekimab, an experimental drug, to determine its effectiveness for people who formerly smoked and now have moderate-to-severe COPD, a lung disease causing breathing problems. Researchers aim to discover if itepekimab can reduce flare-ups, improve lung function, and enhance life quality compared to a placebo, which is a non-active treatment. Participants must have experienced frequent COPD flare-ups and should have stopped smoking for at least six months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that participants should have been on a stable dose of their COPD controller therapy for at least 1 month before screening. It's best to discuss your specific medications with the trial team.

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

Research has shown that itepekimab, a monoclonal antibody, may help treat chronic obstructive pulmonary disease (COPD) and asthma. Early studies suggest itepekimab is generally safe for patients. In asthma studies, it proved effective without causing serious side effects.

Although detailed safety information for COPD patients is limited, itepekimab's progression to this advanced trial stage indicates it has passed initial safety tests. Earlier studies reported no major side effects. So far, itepekimab appears to be a safe option for those considering participation in a clinical trial. ^{1 2 3 4 5}

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

Itepekimab is unique because it targets interleukin-33 (IL-33), a new mechanism of action for treating COPD. While most treatments for COPD, like bronchodilators and corticosteroids, focus on relaxing airways or reducing inflammation, Itepekimab aims to modulate the immune response more upstream by blocking IL-33, which is involved in the inflammation process. This could potentially offer better control over symptoms and disease progression. Researchers are excited because this approach might provide relief for patients who don't respond well to current therapies, offering a new hope for improved lung function and quality of life.

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

This trial will evaluate the effectiveness of itepekimab, a monoclonal antibody, for treating COPD. Participants will receive either itepekimab every 2 weeks, itepekimab every 4 weeks with alternating placebo, or a placebo every 2 weeks. Studies have shown that itepekimab may help treat COPD by targeting a protein called IL-33. In one study, itepekimab successfully reduced the number of COPD flare-ups, which are times when symptoms suddenly worsen. This suggests that itepekimab might help manage COPD symptoms and possibly improve lung function. However, another study showed mixed results, indicating the need for more research to understand its effectiveness. Overall, early evidence appears promising, but additional data will help clarify itepekimab's role in treating COPD. ^{2 3 4 5 6}

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 smokers aged 40-85 with moderate-to-severe COPD who have had at least one exacerbation while on current therapy. They must not be currently smoking, have quit at least 6 months prior, and agree to contraception if applicable. Excluded are those with certain cardiac arrhythmias, active autoimmune diseases or treatments, a current asthma diagnosis, or previous use of itepekimab.

Inclusion Criteria

I have had severe breathing issues that needed steroids or antibiotics.

I've been on a stable asthma treatment for at least 3 months.

I am between 40 and 85 years old.

Exclusion Criteria

I have asthma or had it before I turned 18.

I have previously used itepekimab.

This information may not include all the factors that need to be considered before deciding whether to participate in a clinical trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3-5 weeks

Treatment

Participants receive either itepekimab or placebo subcutaneously every 2 or 4 weeks for up to 52 weeks

24 to 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

20 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term in a double-blinded extension study

What Are the Treatments Tested in This Trial?

Interventions

• Itepekimab SAR440340
• Placebo

Trial Overview The study tests the effectiveness of Itepekimab (SAR440340) against a placebo in reducing the rate of severe COPD flare-ups in participants. It also examines its impact on lung function, symptoms severity, quality of life and collects data on drug safety and how the body processes it.

How Is the Trial Designed?

Group I: Itepekimab Q4W Experimental Treatment 2 Interventions

SC administration of Itepekimab every 4 weeks (Q4W) for up to 52 weeks, with alternating SC administration of matching placebo at the 2-week interval between active IMP

Group II: Itepekimab Q2W Experimental Treatment 1 Intervention

Subcutaneous (SC) administration of Itepekimab every 2 weeks (Q2W) for up to 52 weeks

Group III: Placebo Placebo Group 1 Intervention

SC administration of matching placebo Q2W for up to 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 three-year study involving 290 patients with chronic obstructive pulmonary disease (COPD), inhaled budesonide did not significantly reduce the decline in lung function compared to placebo, with an insignificant difference of only 3.1 ml/year in FEV1 decline.

Budesonide also showed no effect on respiratory symptoms or the frequency of exacerbations, raising questions about the effectiveness of long-term inhaled corticosteroids for treating mild to moderate COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Long-term effect of inhaled budesonide in patients with mild to moderate chronic obstructive lung disease. The Osterbro Study]. Vestbo, J., Sørensen, T., Lange, P., et al.[2006]

Tiotropium significantly improves health-related quality of life and reduces dyspnea in patients with stable COPD compared to both placebo and ipratropium, based on a review of 16 trials involving 16,301 patients.

Tiotropium also lowers the risk of exacerbations and related hospitalizations without increasing the likelihood of serious adverse events, although it does have a higher incidence of dry mouth compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tiotropium for treatment of stable COPD: a meta-analysis of clinically relevant outcomes. Yohannes, AM., Willgoss, TG., Vestbo, J.[2022]

Tezepelumab, a monoclonal antibody approved for severe uncontrolled asthma, significantly improved forced expiratory volume (FEV1) by 0.15 L and reduced asthma exacerbation rates by 0.60 per year compared to placebo, based on a meta-analysis of six trials with 2667 patients.

The treatment was found to have an acceptable safety profile, with no higher incidence of adverse drug reactions compared to placebo, indicating it is a safe option for patients with severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis. Zoumot, Z., Al Busaidi, N., Tashkandi, W., 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 study involving 281 COPD patients, fluticasone propionate significantly reduced the severity of exacerbations compared to placebo, with 60% of patients experiencing moderate or severe exacerbations versus 86% in the placebo group (p<0.001).

Patients treated with fluticasone propionate showed significant improvements in lung function and symptoms, including increased peak expiratory flow and a greater 6-minute walking distance, while the treatment was well-tolerated with minimal adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. International COPD Study Group. Paggiaro, PL., Dahle, R., Bakran, I., et al.[2022]

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]

AZD3199, an ultra-long-acting β2-agonist, demonstrated rapid absorption into the bloodstream within 30 minutes after dosing, with a long half-life of up to 142 hours, indicating its potential for sustained therapeutic effects in asthma and COPD patients.

The drug was well tolerated across all studies, showing no significant safety concerns, which supports its further evaluation as a treatment option for respiratory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of AZD3199, an inhaled ultra-long-acting β2-adrenoreceptor agonist (uLABA). Bjermer, L., Kuna, P., Jorup, C., et al.[2018]

In a 52-week study involving 65 Japanese patients with severe uncontrolled asthma, tezepelumab was found to be safe and well-tolerated, with most adverse events being mild to moderate, and only one case leading to treatment discontinuation.

Tezepelumab significantly reduced asthma exacerbation rates (0.11 per patient-year) and improved lung function and asthma control, with a 71.4% responder rate at Week 52, indicating its efficacy in managing severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study. Shinkai, M., Ebisawa, M., Fukushima, Y., et al.[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 meta-analysis of 1136 patients from the METREX and METREO trials, mepolizumab significantly reduced the annual rate of moderate to severe exacerbations in COPD patients with elevated blood eosinophil counts by 18% compared to placebo.

The study found that higher blood eosinophil counts were associated with greater efficacy of mepolizumab, suggesting that patients with eosinophil counts of ≥150 cells/µL at screening or ≥300 cells/µL in the prior year are more likely to benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO. Pavord, ID., Chapman, KR., Bafadhel, M., et al.[2021]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT04701983

NCT04701983 | Study to Assess the Efficacy, Safety, and ... Primary Objective: Evaluate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate-or-severe COPD exacerbations in former ...

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

Safety and efficacy of itepekimab in patients with moderate- ... Itepekimab, a monoclonal antibody targeting IL-33, demonstrated clinical activity in asthma, with potential in chronic obstructive pulmonary ...

4. clinicaltrials.regeneron.com clinicaltrials.regeneron.com/clinical-trials/a0Mdy00000017lrEAA/nct04701983

Study to Assess the Efficacy, Safety, and Tolerability of ... Trial summary. Primary Objective: Evaluate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate-or-severe COPD ...

5. 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 ...

6. 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 ...