Atuliflapon for Uncontrolled Asthma

(FLASH Trial)

Recruiting at 198 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must be taking: Inhaled corticosteroids, Long-acting β2-agonists

Must not be taking: Systemic corticosteroids, Marketed biologics

Disqualifiers: COVID-19, Pulmonary disease, Cardiac disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

Duration: 12 weeks

666 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing Atuliflapon, a new medication, in adults with moderate to severe uncontrolled asthma. It aims to see if Atuliflapon can better manage asthma symptoms for those who do not respond well to current treatments.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of your current asthma medications, such as inhaled corticosteroids and long-acting β2-agonists, for at least 3 months before starting. However, certain medications like systemic corticosteroids, leukotriene receptor antagonists, and some biologics must be stopped for a specified period before joining the trial.

What data supports the effectiveness of the drug Atuliflapon for uncontrolled asthma?

Research shows that montelukast, a component of Atuliflapon, is effective in treating chronic asthma and is particularly helpful for exercise-induced asthma. This suggests that Atuliflapon may also be beneficial for asthma management. ^{1 2 3 4 5}

How does the drug Atuliflapon differ from other asthma treatments?

Atuliflapon (AZD5718) is unique because it targets leukotrienes, which are substances in the body that can cause asthma symptoms. Unlike many asthma treatments that are inhaled, Atuliflapon is taken orally, which may improve patient compliance. ^{1 2 4 6 7}

Eligibility Criteria

Adults with moderate to severe uncontrolled asthma for over a year, able to perform lung function tests, and on stable asthma medication can join. They must have had at least one severe asthma attack in the past year and be vaccinated against flu/pneumonia. Exclusions include recent drug trials, certain medications like high-dose statins or systemic steroids, liver impairment, other significant diseases, current cancer (except some skin cancers), substance abuse history, pregnancy or breastfeeding.

Inclusion Criteria

My weight is between 50 and 100 kg, and my BMI is between 18 and 30.

My asthma control score is 1.5 or higher.

Your lung function test results in the morning before taking any medication should show that you can exhale a certain amount of air.

Exclusion Criteria

I have not received any live vaccines in the last 4 weeks.

I have not taken strong drugs affecting liver enzymes in the last 4 weeks.

I am on birth control pills that contain ethinyl estradiol.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Lead-in PK

Participants are randomised to Atuliflapon or placebo to assess pharmacokinetics

2 weeks

2 visits (in-person)

Treatment

Participants receive Atuliflapon or placebo once daily for 12 weeks

12 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• AZD5718
• Montelukast
• Placebo

Trial Overview The trial is testing Atuliflapon's effectiveness and safety compared to a placebo over 12 weeks in adults with uncontrolled asthma. It's randomized (participants are assigned by chance), double-blind (neither participants nor researchers know who gets what treatment) and placebo-controlled (compared against an inactive substance).

Participant Groups

Group I: Part 1 (Atuliflapon) Experimental Treatment 1 Intervention

Randomised participants will receive Atuliflapon in Part 1 of the study.

Group II: Lead-in PK cohort (Atuliflapon) Experimental Treatment 1 Intervention

Randomised participants will receive Atuliflapon in Lead-in PK period of the study.

Group III: Lead-in PK cohort (Placebo) Placebo Group 1 Intervention

Randomised participants will receive matching placebo to Atuliflapon in Lead-in PK cohort of the study.

Group IV: Part 1 (Placebo) Placebo Group 1 Intervention

Randomised participants will receive matching placebo to Atuliflapon in Part 1 of the study.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

In the phase 2b PATHWAY study involving 550 adults with severe, uncontrolled asthma, tezepelumab significantly reduced asthma exacerbations by up to 71% and improved lung function and quality of life compared to placebo.

Tezepelumab treatment led to higher rates of patient-reported outcomes, with up to 82% of patients showing improved asthma control and quality of life, indicating its effectiveness in managing severe asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY. Corren, J., Garcia Gil, E., Griffiths, JM., et al.[2021]

Antileukotrienes, including montelukast and zafirlukast, are effective in treating chronic asthma and have shown particular efficacy in exercise-induced asthma, with montelukast being the most studied in children.

All antileukotrienes are generally well tolerated, but zileuton may pose a risk for liver-related side effects; the occurrence of Churg-Strauss syndrome in patients is more likely linked to corticosteroid withdrawal rather than the antileukotrienes themselves.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antileukotrienes in asthma: present situation. García-Marcos, L., Schuster, A.[2021]

A comprehensive analysis of 3,234 asthma drug-related articles from 1982 to 2021 revealed that the United States leads in research output, with the Karolinska Institute in Sweden being the most active institution, indicating a strong global interest in asthma treatment advancements.

Current research hotspots include optimizing existing asthma medications and developing new monoclonal antibodies like omalizumab and mepolizumab, which aim to improve asthma control and safety, particularly for severe asthma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A bibliometric and scientific knowledge map study of the drug therapies for asthma-related study from 1982 to 2021. Zhen, G., Yingying, L., Weifang, X., et al.[2022]

Zafirlukast, when added to standard asthma treatment, showed improvements in pulmonary function and quality of life in patients with stable asthma, with significant increases in morning and evening peak expiratory flow (PEF) values.

In patients experiencing an asthma attack, zafirlukast combined with a reduced dose of glucocorticoids led to better pulmonary function outcomes compared to standard treatment alone, although the differences were not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Influence of zafirlukast on pulmonary functions and quality of life in patients with asthma]. Xiang, XD., Zhou, R., Chen, Y.[2021]

Tezepelumab has shown significant efficacy in treating severe, uncontrolled asthma, as demonstrated in a pooled analysis of the PATHWAY and NAVIGATOR clinical trials, which included a diverse group of participants.

The results indicate that tezepelumab effectively reduces asthma exacerbations and improves lung function, making it a promising treatment option for patients with difficult-to-control asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In severe, uncontrolled asthma, tezepelumab reduced exacerbations over 1 y regardless of type 2 inflammation level. Estrada, RA., Maselli, DJ.[2023]

Leukotriene receptor antagonists (like zafirlukast and montelukast) are effective in treating asthma, significantly improving symptoms, pulmonary function, and reducing the need for other medications, with a 50% reduction in asthma exacerbations compared to placebo.

These medications are well tolerated, have a similar side effect profile to placebo, and their use can lead to over a 50% reduction in healthcare costs associated with asthma management, making them a valuable option for patients with persistent asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asthma controller therapy: role of antileukotrienes, a new therapeutic class. Allegra, L., Canonica, GW., Donner, CF., et al.[2016]

In a study of 53 patients with persistent allergic rhinitis, the combination treatment MP-AzeFlu significantly reduced symptom severity, with a visual analogue scale score dropping from 73.4 mm at baseline to 28.1 mm by day 42, indicating rapid and sustained relief.

Endoscopic evaluations showed substantial improvements in nasal mucosa, with severe edema decreasing from 53.1% to 3.8% and thick discharge from 28.3% to 4.8% after 28 days, confirming the safety and effectiveness of MP-AzeFlu in a real-world setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-life effectiveness of MP-AzeFlu in Irish patients with persistent allergic rhinitis, assessed by visual analogue scale and endoscopy. Kaulsay, R., Nguyen, DT., Kuhl, HC.[2023]

References

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

Tezepelumab improves patient-reported outcomes in patients with severe, uncontrolled asthma in PATHWAY. [2021]

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

Antileukotrienes in asthma: present situation. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A bibliometric and scientific knowledge map study of the drug therapies for asthma-related study from 1982 to 2021. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Influence of zafirlukast on pulmonary functions and quality of life in patients with asthma]. [2021]

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

In severe, uncontrolled asthma, tezepelumab reduced exacerbations over 1 y regardless of type 2 inflammation level. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

Asthma controller therapy: role of antileukotrienes, a new therapeutic class. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Real-life effectiveness of MP-AzeFlu in Irish patients with persistent allergic rhinitis, assessed by visual analogue scale and endoscopy. [2023]