Lunsekimig for Asthma

(AIRPHRODITE Trial)

Recruiting at 36 trial locations

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

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi

Must be taking: ICS, LABA, LAMA, LTRA

Disqualifiers: New pulmonary disease, Smoking, Substance abuse, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

530 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 2, open-label extension study to evaluate the long-term safety and efficacy of lunsekimig in adult participants with moderate-to-severe asthma who have previously completed the parent study. After completion of the parent study, eligible participants will be offered the opportunity to participate in the long-term extension (LTE) study with lunsekimig. The study duration will be up to 100 weeks with a treatment duration being up to 96 weeks.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, you must have a stable background therapy of certain asthma medications to participate.

What data supports the effectiveness of the drug Lunsekimig for asthma?

Research shows that blocking IL-13, a protein involved in airway inflammation, can help reduce asthma attacks and improve lung function in some patients. However, combining IL-13 blocking with other treatments, like IL-4 blocking, might be more effective for asthma control. ^{1 2 3 4 5}

Is Lunsekimig (Anti-IL-13/TSLP) generally safe for humans?

Studies on similar treatments targeting IL-13, like tralokinumab and lebrikizumab, have shown no serious side effects in patients with asthma. These treatments were generally safe, although they did not always meet their effectiveness goals. ^{1 3 4 6 7}

What makes the drug Lunsekimig unique for treating asthma?

Lunsekimig is unique because it targets both IL-13 and TSLP, which are proteins involved in the inflammation process of asthma, potentially offering a novel approach compared to existing treatments that primarily focus on leukotrienes or corticosteroids. ^{8 9 10 11 12}

Eligibility Criteria

This trial is for adults with moderate-to-severe asthma who completed the DRI16762 study. They must be on a stable regimen of medium to high-dose inhaled corticosteroids and up to two other controller meds, just like in the previous study. Participants should agree to long-term follow-up, use contraception if applicable, and not be pregnant or donating gametes.

Inclusion Criteria

I am willing and able to follow the study's schedule and procedures.

I cannot become pregnant.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a subcutaneous injection of lunsekimig according to established dosing interval

96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Lunsekimig

Trial Overview The trial is testing Lunsekimig's long-term safety and effectiveness for those with moderate-to-severe asthma over a period of up to 96 weeks. It's an open-label extension meaning everyone gets Lunsekimig and knows it; there’s no placebo group.

Participant Groups

Group I: Lunsekimig Experimental Treatment 1 Intervention

Participants will receive a subcutaneous injection of lunsekimig according to established dosing interval

Lunsekimig is already approved in China for the following indications:

Approved in China as Lunsekimig for:

• High-risk asthma in adults
• Moderate to severe asthma in adults

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

Findings from Research

Two monoclonal antibodies targeting IL-13, tralokinumab and lebrikizumab, were tested in multiple studies for severe asthma but did not meet their primary efficacy endpoints, despite showing safety with no serious adverse events reported.

In contrast, dupilumab, which blocks both IL-4 and IL-13 signaling, has been effective in reducing asthma exacerbations and improving lung function, suggesting that targeting both pathways may be more beneficial than targeting IL-13 alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma. Marone, G., Granata, F., Pucino, V., et al.[2020]

Tralokinumab, a monoclonal antibody targeting IL-13, has been evaluated in four randomized, placebo-controlled trials for its efficacy and safety in treating severe, uncontrolled asthma, showing promising results.

The pivotal trials (STRATOS 1 and STRATOS 2) identified specific patient subgroups that may benefit most from tralokinumab, while additional studies explored its potential to reduce reliance on oral corticosteroids and assessed long-term safety in Japanese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tralokinumab for the treatment of severe, uncontrolled asthma: the ATMOSPHERE clinical development program. Panettieri, RA., Wang, M., Braddock, M., et al.[2020]

Anti-interleukin 13 therapies significantly reduced the rate of asthmatic exacerbations and improved peak expiratory flow (PEF) in adult asthmatics, based on a systematic review of 8 studies involving 957 patients.

These therapies did not significantly improve lung function measures like FEV1 or reduce eosinophil levels, indicating that while they are effective in reducing exacerbations, their overall impact on asthma control may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Efficacy and Safety of Antiinterleukin 13, a Monoclonal Antibody, in Adult Patients With Asthma: A Systematic Review and Meta-Analysis. Luo, J., Liu, D., Liu, CT.[2022]

The study of CAT-354, a human anti-IL-13 antibody, involved 23 adults with asthma and demonstrated a linear pharmacokinetic profile, with a half-life of 12-17 days and low clearance, indicating it can be safely administered in multiple doses.

Most adverse events were mild to moderate and unrelated to the medication, suggesting that CAT-354 has an acceptable safety profile for treating asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study evaluating the pharmacokinetics, safety and tolerability of repeat dosing with a human IL-13 antibody (CAT-354) in subjects with asthma. Singh, D., Kane, B., Molfino, NA., et al.[2021]

Anti-IL-13 monoclonal antibodies, specifically lebrikizumab and tralokinumab, significantly improve asthma management in uncontrolled asthma patients, as shown in a meta-analysis of five studies with 3476 participants, leading to reduced asthma exacerbations, improved lung function (FEV1), and better quality of life scores.

The safety profile of anti-IL-13 treatments is comparable to placebo, with no significant increase in adverse events, and patients with high periostin levels may benefit the most from this treatment, suggesting that periostin could be a useful biomarker for identifying responsive patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A meta-analysis of anti-interleukin-13 monoclonal antibodies for uncontrolled asthma. Li, H., Wang, K., Huang, H., et al.[2020]

Dupilumab significantly improves lung function and asthma control in patients with moderate to severe asthma, as evidenced by better forced expiratory volume and asthma control questionnaire scores over 12 and 24 weeks in 13 trials.

The treatment is generally safe, showing no significant increase in adverse events compared to placebo, although it was associated with higher blood eosinophil levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab efficacy and safety in patients with moderate to severe asthma: A systematic review and meta-analysis. Zaazouee, MS., Alwarraqi, AG., Mohammed, YA., et al.[2022]

Interleukin (IL)-13 and IL-4 are key targets for treating TH2-mediated asthma, as they play significant roles in the disease's inflammatory processes, including IgE synthesis and airway remodeling.

Anti-IL-13 treatments, like lebrikizumab, and anti-IL-4 treatments, such as dupilumab, have shown promise in reducing asthma severity and exacerbations, but identifying specific biomarkers for patient response is crucial for optimizing these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Critical Evaluation of Anti-IL-13 and Anti-IL-4 Strategies in Severe Asthma. Bagnasco, D., Ferrando, M., Varricchi, G., et al.[2022]

Leukotriene modifiers, a new class of asthma medications, have been shown to effectively improve pulmonary function, reduce symptoms, and decrease the need for rescue medications in patients with asthma, based on controlled clinical trials.

These medications are generally safe and well tolerated, with side effects similar to placebo, although there is a noted association with Churg-Strauss Syndrome, which may be related to reducing corticosteroid doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in the management of asthma using leukotriene modifiers. Kemp, JP.[2021]

In a 13-week study involving 454 participants aged 12 to 68, zafirlukast significantly reduced daytime asthma symptoms, nighttime awakenings, and beta2-agonist use compared to placebo, indicating its efficacy in managing asthma.

Zafirlukast also improved quality of life across various domains, with a safety profile similar to that of placebo, suggesting it is a well-tolerated treatment option for patients with moderate asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zafirlukast improves asthma symptoms and quality of life in patients with moderate reversible airflow obstruction. Nathan, RA., Bernstein, JA., Bielory, L., et al.[2021]

Leukotriene receptor antagonists (LTRAs) like montelukast and zafirlukast are effective in treating asthma, showing bronchodilating and anti-inflammatory properties that complement inhaled corticosteroids, especially in patients with moderate asthma.

Clinical studies indicate that LTRAs can improve asthma control and allow for reduced corticosteroid dosages, with montelukast providing similar benefits to inhaled corticosteroids in patients with mild persistent asthma over a 6-week treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leukotriene receptor antagonists in the treatment of asthma: an update. Balzano, G., Fuschillo, S., Gaudiosi, C.[2019]

In a study of 35 patients with allergic rhinitis and asthma, the leukotriene receptor antagonist zafirlukast significantly reduced symptoms of both conditions after 2 weeks of treatment during the grass pollen season.

Zafirlukast improved nasal resistance and ciliary beat frequency, while also decreasing eosinophil counts in nasal lavage fluid, indicating its potential effectiveness in managing inflammation associated with these respiratory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of zafirlukast on bronchial asthma and allergic rhinitis. Piatti, G., Ceriotti, L., Cavallaro, G., et al.[2021]

New leukotriene modulators, such as montelukast, zafirlukast, and zileuton, have been developed to improve asthma control by reducing symptoms and the need for rescue medications.

These medications are effective for patients with mild intermittent to moderate persistent asthma, as they help improve pulmonary function and overall management of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive asthma management: guidelines for clinicians. Kemp, JP.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Tralokinumab for the treatment of severe, uncontrolled asthma: the ATMOSPHERE clinical development program. [2020]

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

The Efficacy and Safety of Antiinterleukin 13, a Monoclonal Antibody, in Adult Patients With Asthma: A Systematic Review and Meta-Analysis. [2022]

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

A phase 1 study evaluating the pharmacokinetics, safety and tolerability of repeat dosing with a human IL-13 antibody (CAT-354) in subjects with asthma. [2021]

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

A meta-analysis of anti-interleukin-13 monoclonal antibodies for uncontrolled asthma. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Dupilumab efficacy and safety in patients with moderate to severe asthma: A systematic review and meta-analysis. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Critical Evaluation of Anti-IL-13 and Anti-IL-4 Strategies in Severe Asthma. [2022]

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

Recent advances in the management of asthma using leukotriene modifiers. [2021]

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

Zafirlukast improves asthma symptoms and quality of life in patients with moderate reversible airflow obstruction. [2021]

10. Denmark pubmed.ncbi.nlm.nih.gov

Leukotriene receptor antagonists in the treatment of asthma: an update. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of zafirlukast on bronchial asthma and allergic rhinitis. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Comprehensive asthma management: guidelines for clinicians. [2019]