Itepekimab for COPD

(AERIFY-2 Trial)

Recruiting at 650 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, Pulmonary disease, Hypertension, 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: 52 weeks

1210 Participants Needed

Trial Summary

What is the purpose of this trial?

Primary Objective: Primary population (former smokers cohort): * Evaluate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate-or-severe COPD exacerbations in former smokers with moderate-to-severe COPD Secondary Objectives: Primary population (former smokers cohort): * Evaluate the efficacy of itepekimab compared with placebo on pulmonary function in former smokers with moderate-to-severe COPD * Evaluate the efficacy of itepekimab compared with placebo on occurrence of acute exacerbation of COPD (AECOPD) in former smokers with moderate-to-severe COPD * Evaluate the efficacy of itepekimab compared with placebo on severe AECOPD in former smokers with moderate-to-severe COPD * Evaluate the efficacy of itepekimab compared with placebo on corticosteroid-treated AECOPD in former smokers with moderate-to-severe COPD * Evaluate the efficacy of itepekimab compared with placebo on respiratory symptoms in former smokers with moderate-to-severe COPD * Evaluate the efficacy of itepekimab compared with placebo on Forced Expiratory Volume in 1 second (FEV1) slope in former smokers with moderate-to-severe COPD * Evaluate the efficacy of itepekimab compared with placebo on health-related quality of life (HRQoL) as assessed by St. George's Respiratory Questionnaire (SGRQ) in former smokers with moderate-to-severe COPD * Evaluate the safety and tolerability of itepekimab in former smokers with moderate-to-severe COPD * Evaluate the pharmacokinetic (PK) profile of itepekimab in former smokers with moderate-to-severe COPD * Evaluate immunogenicity to itepekimab in former smokers with moderate-to-severe COPD Secondary population (current smokers cohort) * Estimate the efficacy of itepekimab compared with placebo on the annualized rate of acute moderate or severe COPD exacerbations in current smokers with moderate-to-severe COPD * Estimate the efficacy of itepekimab compared with placebo on pulmonary function in current smokers with moderate-to-severe COPD * Estimate the safety and tolerability of itepekimab in current smokers with moderate-to-severe COPD * Estimate the PK profile of itepekimab in current smokers with moderate to severe COPD * Estimate immunogenicity to itepekimab in current smokers with moderate-to-severe COPD

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have been on a stable dose of their COPD controller therapy for at least one month before the trial.

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

Itepekimab, a drug that targets a protein called IL-33, has shown promise in reducing inflammation in asthma, which is a condition similar to COPD. In a study, it was well-tolerated and showed potential for treating COPD, suggesting it might help reduce lung inflammation in COPD patients as well. ^{1 2 3 4 5}

Is itepekimab safe for humans?

Itepekimab has been tested in healthy adults and patients with asthma, showing it was well-tolerated with no significant safety issues reported. In studies, it did not cause treatment-emergent anti-drug antibody responses, indicating a good safety profile. ^{1 2 6 7 8}

How is the drug Itepekimab different from other COPD treatments?

Itepekimab is unique because it targets a specific part of the immune system involved in inflammation, which is different from most COPD treatments that focus on opening airways or reducing symptoms. This approach may offer a new way to manage COPD by addressing the underlying inflammation. ^{9 10 11 12 13}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

This trial is for adults aged 40-85 with moderate-to-severe COPD who are either current or former smokers. They must have had at least one severe exacerbation requiring hospitalization or two moderate ones treated with steroids in the past year, and be on a stable dose of standard COPD therapy.

Inclusion Criteria

I am a current smoker and not planning to quit soon.

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

I have had severe lung flare-ups needing more than a day's hospital stay.

Exclusion Criteria

I have asthma or had it before I turned 18.

I have not vaped any products in the last 6 months.

I do not have active or latent TB, nor have I been in close contact with TB patients recently.

Timeline

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

52 weeks

Bi-weekly or monthly visits for subcutaneous administration

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

Treatment Details

Interventions

• Itepekimab SAR440340
• Placebo

Trial Overview The study tests Itepekimab's effectiveness compared to a placebo in reducing the rate of severe COPD flare-ups, improving lung function, and enhancing quality of life among both current and former smokers with COPD.

Participant Groups

Group I: Itepekimab Q4W in former smokers 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 in former smokers Experimental Treatment 1 Intervention

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

Group III: Itepekimab Q2W in current smokers Experimental Treatment 1 Intervention

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

Group IV: Placebo in current smokers Placebo Group 1 Intervention

SC administration of matching placebo Q2W for 52 weeks

Group V: Placebo in former smokers 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

Findings from Research

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 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]

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 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]

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]

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]

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]

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]

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]

References

1. 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]

2. 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]

3. England 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. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO. [2021]

5. Denmark pubmed.ncbi.nlm.nih.gov

[Long-term effect of inhaled budesonide in patients with mild to moderate chronic obstructive lung disease. The Osterbro Study]. [2006]

6. England pubmed.ncbi.nlm.nih.gov

One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study. [2023]

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

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

8. New Zealand pubmed.ncbi.nlm.nih.gov

Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis. [2022]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Efficacy and safety of once-daily inhaled umeclidinium/vilanterol in Asian patients with COPD: results from a randomized, placebo-controlled study. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Improved delivery of ipratropium bromide/fenoterol from Respimat Soft Mist Inhaler in patients with COPD. [2019]

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

Tiotropium for treatment of stable COPD: a meta-analysis of clinically relevant outcomes. [2022]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical pharmacokinetics of AZD3199, an inhaled ultra-long-acting β2-adrenoreceptor agonist (uLABA). [2018]

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

Preventing Clinically Important Deterioration of COPD with Addition of Umeclidinium to Inhaled Corticosteroid/Long-Acting &#946;2-Agonist Therapy: An Integrated Post Hoc Analysis. [2023]