AZD8630 for Uncontrolled Asthma

(Levante Trial)

Recruiting at 204 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 steroids, Biologics

Disqualifiers: COPD, HIV, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

516 Participants Needed

Trial Summary

What is the purpose of this trial?

A dose range-finding study to assess the efficacy and safety of multiple dose levels of AZD8630 administered via a dry powder inhaler in adults with uncontrolled asthma at risk of exacerbations, receiving medium -to -high dose inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it requires that you are compliant with your asthma background medication. If you are taking systemic steroids or certain biologics, you may need to stop them before joining the trial.

What data supports the effectiveness of the drug AZD8630 for uncontrolled asthma?

The research on tezepelumab, a drug used for severe, uncontrolled asthma, shows it can reduce asthma attacks by up to 71% and improve lung function and quality of life. This suggests that similar treatments targeting severe asthma may also be effective. ^{1 2 3 4 5}

How is the drug AZD8630 different from other asthma treatments?

AZD8630 is unique because it may offer a new approach for patients with uncontrolled asthma who do not respond well to standard treatments like inhaled corticosteroids and long-acting beta-agonists, addressing a significant unmet need in reducing reliance on systemic steroids. ^{2 6 7 8 9}

Research Team

Njira Lugogo

Principal Investigator

Univeristy of Michigan Hospital, Ann Arbor, MI, US

Eligibility Criteria

Adults with uncontrolled asthma who are still having issues despite using medium to high doses of inhaled steroids and long-acting inhalers. They must have had at least one severe asthma attack in the past year.

Inclusion Criteria

I am between 18 and 80 years old.

I have been diagnosed with asthma for over a year.

Pre-BD FEV1 ≥ 40% at both Visit 1 and Visit 2

Exclusion Criteria

My recent health checks showed some abnormal results.

I have a significant lung condition that is not asthma.

I have a history of hepatitis B, C, or HIV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inhaled AZD8630 or placebo once daily for 12 weeks

12 weeks

Weekly visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Optional Safety Extension

Participants may continue treatment for up to 52 weeks in an optional safety extension study

52 weeks

Treatment Details

Interventions

• AZD8630

Trial Overview The trial is testing different doses of a new drug called AZD8630, given through an inhaler, to see if it's effective and safe for people whose asthma isn't well-controlled by their current medications.

Participant Groups

Group I: AZD8630 dose C Experimental Treatment 2 Interventions

Inhaled AZD8630 administered at a dose C

Group II: AZD8630 dose B Experimental Treatment 2 Interventions

Inhaled AZD8630 administered at a dose B

Group III: AZD8630 dose A Experimental Treatment 2 Interventions

Inhaled AZD8630 administered at a dose A

Group IV: Placebo Placebo Group 2 Interventions

Inhaled placebo

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]

In a study of 774 asthma patients at specialty clinics, 53% were found to have uncontrolled asthma despite using inhaled corticosteroids and long-acting β2-agonists, indicating a significant gap in effective management.

Patients with uncontrolled asthma reported worse health-related quality of life, more respiratory illnesses, and higher rates of asthma exacerbations and hospitalizations, highlighting the need for better treatment strategies and adherence to guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence: Patient views on asthma in respiratory specialist clinics in America. Oppenheimer, J., Slade, DJ., Hahn, BA., et al.[2021]

Omalizumab, an anti-IgE monoclonal antibody, significantly reduced asthma exacerbations by 38% and emergency visits by 47% in patients with severe persistent asthma, based on data from 4308 patients across seven studies.

The efficacy of omalizumab was consistent across various demographic groups, with the greatest benefits observed in patients with more severe asthma, indicating its potential as a crucial treatment option for those inadequately controlled by standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. Bousquet, J., Cabrera, P., Berkman, N., et al.[2022]

Asthma action plans (AAPs) are effective in reducing healthcare use and improving quality of life, yet less than 25% of patients receive them due to challenges in prescribing 'yellow zone' instructions for acute asthma control.

The study developed an evidence-based tool to enhance the delivery of AAPs, providing clear guidelines for increasing inhaled corticosteroid doses during acute episodes, which addresses existing gaps in current asthma management practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evidence-based, point-of-care tool to guide completion of asthma action plans in practice. Kouri, A., Boulet, LP., Kaplan, A., et al.[2018]

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]

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 study of 349 adults with refractory asthma, improvements in lung function were observed, along with reductions in hospital admissions and unscheduled healthcare visits, indicating that current treatments are having a positive impact.

Despite the use of maintenance oral corticosteroids, most steroid-sparing agents showed limited effectiveness, highlighting a significant need for new therapies that can reduce reliance on systemic steroids in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical management and outcome of refractory asthma in the UK from the British Thoracic Society Difficult Asthma Registry. Sweeney, J., Brightling, CE., Menzies-Gow, A., et al.[2022]

In a Phase IIb study involving 1,140 patients with persistent allergic asthma, the addition of AZD1981 to standard inhaled corticosteroids and long-acting β2-agonists did not result in significant improvements in lung function compared to placebo, particularly at the highest dose of 400 mg twice daily.

AZD1981 was well tolerated, with a safety profile similar to that of the placebo, indicating that while it may not enhance asthma control, it does not pose additional risks to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the CRTh2 antagonist AZD1981 as add-on therapy to inhaled corticosteroids and long-acting β2-agonists in patients with atopic asthma. Bateman, ED., O'Brien, C., Rugman, P., et al.[2022]

In a randomized trial with 246 patients suffering from severe allergic asthma, omalizumab significantly improved asthma control, allowing for a greater reduction in inhaled corticosteroid doses compared to placebo (60% vs. 50%).

Omalizumab not only enabled a reduction in corticosteroid use but also improved asthma symptoms and quality of life, without increasing the need for rescue medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Holgate, ST., Chuchalin, AG., Hébert, J., et al.[2022]

References

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

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

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

Real-world evidence: Patient views on asthma in respiratory specialist clinics in America. [2021]

3. Denmark pubmed.ncbi.nlm.nih.gov

The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. [2022]

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

An evidence-based, point-of-care tool to guide completion of asthma action plans in practice. [2018]

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

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

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

Clinical management and outcome of refractory asthma in the UK from the British Thoracic Society Difficult Asthma Registry. [2022]

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

Efficacy and safety of the CRTh2 antagonist AZD1981 as add-on therapy to inhaled corticosteroids and long-acting β2-agonists in patients with atopic asthma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. [2022]