Lunsekimig for Asthma
(AIRLYMPUS Trial)
Recruiting in Palo Alto (17 mi)
+69 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Sanofi
Disqualifiers: Severe lung diseases, Immunosuppression, Active TB, others
Prior Safety Data
Breakthrough Therapy
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This is a parallel-group, Phase 2, randomized, double-blind, placebo-controlled, 2-arm study for the treatment of asthma.
The purpose of this study is to assess the efficacy, safety, and tolerability of add-on therapy with SC lunsekimig compared with placebo in male and female participants (aged 18 to 80 years, inclusive) with asthma, who are not currently eligible for biologic treatments.
Study details include:
* The study duration will be approximately 64 weeks for participants not transitioning into the LTS study and approximately 60 weeks for participants transitioning into the LTS study.
* The investigational treatment duration will be up to approximately 52 weeks.
* The number of visits will be 18.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.
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 and IL-4 blocking might be more effective, as seen with another drug, dupilumab, which improves lung function and reduces asthma attacks.
12345Is Lunsekimig (Anti-IL-13/TSLP) safe for humans?
Studies on similar treatments targeting IL-13, like tralokinumab and lebrikizumab, have shown no serious side effects in asthma patients. Dupilumab, which also affects IL-13, is generally safe with minimal side effects. These findings suggest that treatments targeting IL-13 are generally safe for humans.
13467What 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.
89101112Eligibility Criteria
This trial is for adults aged 18 to 80 with high-risk asthma who aren't eligible for biologic treatments. Participants will be involved in the study for about a year, with up to 18 visits.Inclusion Criteria
Pre-BD FEV1 of equal or more than 40% of predicted normal (by Global Lung Function Initiative [GLI] standards) at Screening (Visit 1)
I had at least one asthma attack in the last year.
I have had asthma diagnosed by a doctor for over a year.
Exclusion Criteria
I do not have severe illnesses like heart failure or kidney disease that would stop me from joining the study.
I do not have active or latent TB, nor have I been recently vaccinated for TB.
I do not have severe lung diseases like COPD that could affect my breathing.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive subcutaneous injections of lunsekimig or placebo every 4 weeks
52 weeks
13 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
8-12 weeks
Long-term follow-up (optional)
Participants may transition into a long-term study for continued monitoring
4 weeks
Participant Groups
The trial is testing Lunsekimig as an add-on therapy compared to a placebo. It's double-blind, meaning neither participants nor researchers know who gets the real treatment or placebo during the study.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: LunsekimigExperimental Treatment4 Interventions
Participants will receive lunsekimig (SC injection) every 4 weeks
Group II: PlaceboPlacebo Group4 Interventions
Participants will receive placebo (SC injection) every 4 weeks
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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Helix Biomedics- Site Number : 8400005Boynton Beach, FL
Innovations Biotech- Site Number : 8400044Miami, FL
Clinical Research Associates of Central PA- Site Number : 8400013DuBois, PA
Investigational Site Number : 1240011Kelowna, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
SanofiLead Sponsor
References
The Intriguing Role of Interleukin 13 in the Pathophysiology of Asthma. [2020]Approximately 5-10% of asthmatic patients worldwide suffer from severe asthma. Experimental and clinical studies have demonstrated that IL-13 is an important cytokine in chronic airways inflammation. IL-13 is involved in Th2 inflammation and has been identified as a possible therapeutic target in the treatment of asthma. Two different human monoclonal antibodies (mAbs) anti-IL-13 (tralokinumab and lebrikizumab) block binding and signaling of IL-13 to its receptors, IL-13Rα1 and IL-13Rα2. Several randomized, double-blind, placebo-controlled multicenter studies have evaluated the safety and efficacy of tralokinumab and lebrikizumab in the treatment of adult patients with severe asthma, but all have failed to meet their primary endpoints. No serious adverse events related to the treatment with these anti-IL-13 mAbs have been reported in these studies. These negative clinical results contrast with positive findings from blocking IL-13 signaling in experimental models of asthma, raising doubts about the transferrable value of some models. Interestingly, dupilumab, a mAb which blocks both IL-4 and IL-13 signaling reduces exacerbation rates and improves lung function in severe asthmatics. These results suggest that IL-4 and IL-13 share some, but not all functional activities in airway inflammation. Tralokinumab might show efficacy in a highly selected cohort of asthmatics characterized by overexpression of IL-13.
Tralokinumab for the treatment of severe, uncontrolled asthma: the ATMOSPHERE clinical development program. [2020]Tralokinumab, a fully human IgG4 monoclonal antibody, specifically neutralizes IL-13. The ATMOSPHERE clinical development program comprised four randomized, placebo-controlled clinical trials and an open-label study that aimed to assess the efficacy and safety of tralokinumab for the treatment of severe, uncontrolled asthma. The two pivotal trials (STRATOS 1 and STRATOS 2; NCT02161757 and NCT02194699) evaluated the efficacy and safety of tralokinumab, with STRATOS 1 identifying a subgroup most likely to demonstrate enhanced response to treatment. Further trials have assessed the ability of tralokinumab to reduce oral corticosteroid use (TROPOS; NCT02281357) and determined its mechanistic effects (MESOS; NCT02449473). An open-label study in Japanese individuals (NCT02902809) assessed the long-term safety and tolerability of tralokinumab in this population.
The Efficacy and Safety of Antiinterleukin 13, a Monoclonal Antibody, in Adult Patients With Asthma: A Systematic Review and Meta-Analysis. [2022]Effects of antiinterleukin 13 therapies in patients with asthma remain inconsistent. Therefore, we aimed to further clarify the efficacy and safety of antiinterleukin 13 therapies in adult asthmatics by a systematic review and meta-analysis.Randomized controlled trials which reported pulmonary functions, fraction of exhaled nitric oxide (FeNO), Asthma Control Questionnaire (ACQ), rescue use of short-acting-β-agonist (SABA), and rate of asthmatic exacerbation and adverse events were identified in Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), American College of Physician (ACP) Journal Club, and ISI Web of Science, reference lists and by manual searches. Randomized-effect models were used in meta-analysis to calculate pooled mean difference and relative risks (RR).Eight studies with 957 patients were enrolled. Systematic review showed that treatment with antiinterleukin 13 antibodies could significantly improve peak expiratory flow (PEF), decrease FeNO and asthmatic exacerbation, but could not decrease blood and sputum eosinophil levels, improve FEV1, inhibit methacholine PC20, or reduce ACQ scores. Two studies reported opposite results in reducing rescue use of SABA. Meta-analysis showed that antiinterleukin 13 monoclonal therapies could significantly decrease asthmatic exacerbation (RR 0.55, 95% CI: 0.31-0.96, z = 2.10, P = 0.04), but did not significantly improve the FEV1 (95% CI: -1.03 to 2.22, z = 0.72, P = 0.47) or increasing adverse events (RR 1.00, 95% CI: 0.91-1.10, z = 0.00, P = 1.00).Antiinterleukin 13 monoclonal therapies could be safely used to improve PEF, decrease FeNO and asthmatic exacerbation, and probably reduce rescue use of SABA, but could not decrease blood and sputum eosinophil levels, improve FEV1, inhibit methacholine PC20, or reduce ACQ scores.
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]IL-13 has been implicated in the development of airway inflammation and hyperresponsiveness. This study investigated the multiple-dose pharmacokinetics and safety profile of human anti-IL-13 antibody (CAT-354) in adults with asthma.
A meta-analysis of anti-interleukin-13 monoclonal antibodies for uncontrolled asthma. [2020]More and more clinical trials have tried to assess the clinical benefit of anti-interleukin (IL)-13 monoclonal antibodies for uncontrolled asthma. The aim of this study is to evaluate the efficacy and safety of anti-IL-13 monoclonal antibodies for uncontrolled asthma. Major databases were searched for randomized controlled trials comparing the anti-IL-13 treatment and a placebo in uncontrolled asthma. Outcomes, including asthma exacerbation rate, forced expiratory volume in 1 second (FEV1), Asthma Quality of Life Questionnaire (AQLQ) scores, rescue medication use, and adverse events were extracted from included studies for systematic review and meta-analysis. Five studies involving 3476 patients and two anti-IL-13 antibodies (lebrikizumab and tralokinumab) were included in this meta-analysis. Compared to the placebo, anti-IL-13 treatments were associated with significant improvement in asthma exacerbation, FEV1 and AQLQ scores, and reduction in rescue medication use. Adverse events and serious adverse events were similar between two groups. Subgroup analysis showed patients with high periostin level had a lower risk of asthma exacerbation after receiving anti-IL-13 treatment. Our study suggests that anti-IL-13 monoclonal antibodies could improve the management of uncontrolled asthma. Periostin may be a good biomarker to detect the specific subgroup who could get better response to anti-IL-13 treatments. In view of blocking IL-13 alone is possibly not enough to achieve asthma control because of the overlapping pathophysiological roles of IL-13/IL-4 in inflammatory pathways, combined blocking of IL-13 and IL-4 with monoclonal antibodies may be more encouraging.
A Critical Evaluation of Anti-IL-13 and Anti-IL-4 Strategies in Severe Asthma. [2022]Asthma is a high-prevalence disease, still accounting for mortality and high direct and indirect costs. It is now recognized that, despite the implementation of guidelines, a large proportion of cases remain not controlled. Certainly, adherence to therapy and the education of patients remain the primary objective, but the increasingly detailed knowledge about the pathogenic mechanisms and new biotechnologies offer the opportunity to better address and treat the disease. Interleukin (IL)-13 and IL-4 appear as the most suitable targets to treat the T helper 2 (TH2)-mediated forms (endotypes) of asthma. IL-13 and IL-4 partly share the same receptor and signaling pathways and both are deeply involved in immunoglobulin E (IgE) synthesis, eosinophil activation, mucus secretion and airways remodeling. Several anti-IL-13 strategies have been proposed (anrukinzumab, lebrikizunab and tralokinumab), with relevant clinical results reported with lebrikizumab. Such studies facilitate better definition of the possible predictive markers of response to a specific treatment (e.g. eosinophils, total IgE, fraction of exhaled nitric oxide and periostin). In parallel, anti-IL-4 strategies have been attempted (pascolizumab, pitakinra and dupilumab). So far, dupilumab was reported capable of reducing the severity of asthma and the rate of exacerbations. IL-13 and IL-4 are crucial in TH2-mediated inflammation in asthma, but it remains clear that only specific endotypes respond to these treatments. Although the use of anti-IL-14 and anti-IL-13 strategies is promising, the search for appropriate predictive biomarkers is urgently needed to better apply biological treatments.
Dupilumab efficacy and safety in patients with moderate to severe asthma: A systematic review and meta-analysis. [2022]Background: Dupilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-4 receptor and inhibits the signaling of IL-4 and IL-13. It is approved for treating asthma and other type-2 inflammatory diseases. There is a conflict in the literature regarding the safety and efficacy of dupilumab. Thus, we aimed to assess the safety and efficacy of dupilumab in patients with moderate to severe asthma. Methods: Six databases (PubMed, Embase, Scopus, Web of Science, Cochrane library, and clinicaltrials.gov registry) were searched until January 2022. We included randomized controlled trials that compared dupilumab with the placebo in moderate to severe asthma patients. We extracted the data at 12 and 24 weeks and analyzed them using review manager 5.4. Findings: Thirteen trials were included. Dupilumab significantly improved the forced expiratory volume in 1 s, asthma control questionnaire score, the fraction of exhaled nitric oxide level, and immunoglobulin E level at 12 and 24 weeks (p < 0.05). However, it was associated with increased blood eosinophils at 12 and 24 weeks. Dupilumab was generally a safe agent for asthmatic patients. It showed no significant difference compared with the placebo regarding most adverse events. Conclusion: Dupilumab improves pulmonary function and reduces local and systemic inflammatory markers with minimal adverse events in patients with moderate to severe asthma.
Comprehensive asthma management: guidelines for clinicians. [2019]Asthma is a chronic inflammatory disease characterized by reversible airway obstruction and nonspecific airway hyperreactivity. Asthma is managed in steps according to disease symptoms and severity. Treatment goals are to decrease symptoms, improve pulmonary function, and reduce overall morbidity and the associated cost of medical care. Antiasthma drugs are a key component of asthma management that are classified as either long-term-control medications that control symptoms and prevent disease exacerbations, or quick-relief medications that rapidly relieve airway obstruction and acute asthma symptoms. Several new leukotriene (LT) modulators have been developed that promise to improve asthma control, including LT receptor antagonists montelukast and zafirlukast and the 5-lipoxygenase inhibitor zileuton. Each decreases symptoms and the use of rescue medication, and improves pulmonary function in patients with mild intermittent to moderate persistent asthma.
Recent advances in the management of asthma using leukotriene modifiers. [2021]Asthma is a chronic inflammatory disease of the airways that affects approximately 100 million people worldwide. In order to reduce symptoms, improve pulmonary function, and decrease morbidity, current treatment guidelines emphasize the importance of controlling the underlying inflammation in patients with asthma. Leukotrienes are leukocyte-generated lipid mediators that promote airway inflammation. Recognition of the importance of leukotrienes in the pathogenesis of asthma has led to the development of leukotriene modifiers, the first new class of drugs for the treatment of asthma to become available in 25 years. Controlled clinical trials with the four currently used leukotriene modifiers (montelukast, zafirlukast, and zileuton in the US and pranlukast in Japan) have established their efficacy in improving pulmonary function, reducing symptoms, decreasing night-time awakenings, and decreasing the need for rescue medications. They exert anti-inflammatory effects that attenuate cellular infiltration and bronchial hyperresponsiveness and complement the anti-inflammatory properties of inhaled corticosteroids. In patients with moderate and severe asthma, they permit tapering of the corticosteroid dose. In patients with exercise-induced asthma, leukotriene modifiers limit the decline in and quicken the recovery of pulmonary functions without the tolerance issues seen with chronic long-acting beta(2)-adrenoceptor agonist use. In patients with aspirin (acetylsalicylic acid)-induced asthma, they improve pulmonary function and shift the dose response curve to the right, reducing the patient's response to aspirin. In patients with seasonal allergic rhinitis, with or without concomitant asthma, they improve nasal, eye, and throat symptoms as well as quality of life. Leukotriene modifiers are generally safe and well tolerated with adverse effect profiles similar to that of placebo. The one safety issue raised with leukotriene modifiers, Churg-Strauss Syndrome, appears to be the unmasking of an already present syndrome that is manifested when the leukotriene modifiers permit corticosteroid doses to be reduced. Although current treatment guidelines recommend their use in patients with mild persistent asthma, these guidelines were developed just as leukotriene modifiers were coming to the market, before much of the clinical efficacy data were published. Because asthma is a heterogeneous disease, the different asthma phenotypes respond differently to therapies; consequently asthma therapy needs to be individualized. Leukotriene modifiers increase the therapeutic options for patients with asthma and, based on recent data, it is expected that future guidelines will describe expanded uses for these agents in clinical circumstances where these drugs are effective.
Leukotriene receptor antagonists in the treatment of asthma: an update. [2019]Leukotriene receptor antagonists (LTRAs), such as montelukast and zafirlukast, have been demonstrated in a number of studies to possess bronchodilating and anti-inflammatory properties, that make these drugs ideal candidates for the treatment of asthma. The last 1998-updating of the GINA Guidelines for the diagnosis and therapy of asthma recommends the use of LTRAs in the treatment of moderate and mild asthma. In patients with moderate asthma not completely controlled with moderate doses of inhaled corticosteroids, the addition of a LTRA is indicated in alternative to either the increase of the inhaled corticosteroid dose or the addition of an inhaled long-acting beta2-agonist. Both in vitro and in vivo evidences indicate that LTRAs possess an anti-inflammatory activity that is presumably complementary to that presented by corticosteroids. Moreover, clinical studies show that the addition of an LTRA, montelukast, is able to improve clinical and functional indexes in patients with asthma not controlled with inhaled corticosteroids, and to allow a reduction in corticosteroid dosage in patients with asthma well controlled by inhaled corticosteroids. In patients with mild persistent asthma monotherapy with an LTRA is indicated in alternative to a low-dose inhaled corticosteroid, an inhaled cromone, or an oral slow-release theophylline. Previous clinical studies in patients with mild to moderate asthma had demonstrated that monotherapy with LTRAs is able to improve airway function, asthma symptoms, use of as-needed medications, exacerbation rate, and quality of life, without evidence of tolerance with prolonged use. Recently, in a subgroup analysis of patients with mild persistent asthma, a 6-week treatment with oral montelukast or inhaled beclomethasone gave similar improvements in "rescue-free" days, days with well controlled asthma, FEV1, blood eosinophils, beta-agonist use, and nocturnal awakes due to asthma.
Effects of zafirlukast on bronchial asthma and allergic rhinitis. [2021]Asthma and allergic rhinitis are common conditions, occurring with increasing prevalence and frequently coexist. In both conditions histamine and cysteinil leukotrienes are important pathogenic inflammatory mediators. We evaluated the effects of the leukotriene receptor antagonist zafirlukast, 20mg administered twice daily for 2 weeks, in patients with allergic rhinitis and bronchial asthma during the grass pollen season. Patients underwent skin prick testing, spirometry, rhinomanometry, mucus transport test with saccharine, nasal epithelial brushing to study ciliary beat and, finally, nasal lavage.Thirty-five subjects completed the study. At the end of the study period, zafirlukast significantly reduced asthma and rhinitis symptoms (P
Zafirlukast improves asthma symptoms and quality of life in patients with moderate reversible airflow obstruction. [2021]Previous trials demonstrated the effectiveness of the leukotriene receptor antagonist zafirlukast in patients with mild-to-moderate asthma.