Benralizumab for Asthma

(CHINOOK Trial)

Recruiting at 28 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: AstraZeneca

Must be taking: Inhaled corticosteroids, Long acting B2-agonist

Must not be taking: Immunosuppressives, Biologics

Disqualifiers: Current smokers, Cancer, Life-threatening asthma, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

Duration: 48 weeks

81 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to evaluate effect of benralizumab on structural and lung function changes in severe eosinophilic asthmatics. Changes will be assessed over 48 week treatment period in patients with persistent symptoms despite standard therapy of inhaled corticosteroids (ICS) plus long acting B2-agonist (LABA) with or without additional controller medication. Patients who complete treatment will enter 4 weeks follow-up period.

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 be on a high-dose inhaled corticosteroid plus a long-acting B2-agonist for at least 3 months before joining the trial.

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

Research shows that Benralizumab can significantly reduce asthma attacks and improve lung function in patients with severe asthma. It works by targeting and reducing eosinophils, a type of white blood cell that can cause inflammation in asthma. ^{1 2 3 4 5}

Is Benralizumab safe for humans?

Benralizumab, also known as Fasenra, has been shown to be generally safe and well-tolerated in clinical trials for severe eosinophilic asthma. Studies have demonstrated its safety in both healthy individuals and patients with asthma, with no major safety concerns reported. ^{1 2 6 7 8}

How is the drug Benralizumab different from other asthma treatments?

Benralizumab is unique because it is a monoclonal antibody that targets the interleukin-5 receptor, which helps reduce the number of eosinophils (a type of white blood cell involved in inflammation) in the body. This makes it particularly effective for patients with severe eosinophilic asthma, a type of asthma that is not well controlled by standard treatments like inhaled corticosteroids and long-acting beta-agonists. ^{1 2 3 6 9}

Research Team

Mario Castro, MD

Principal Investigator

University of Kansas School of Medicine 3901 Rainbow Blvd. Kansas City, KS 66160, USA

Eligibility Criteria

Adults aged 18-70 with severe eosinophilic asthma, not well-controlled despite using inhaled steroids and long-acting beta agonists. They must have specific levels of blood eosinophils and less than 12 asthma attacks in the past six months. Excluded are those who've had certain treatments like benralizumab or bronchial thermoplasty recently, current smokers, cancer patients, pregnant women, or those on immunosuppressants.

Inclusion Criteria

I've had fewer than 12 asthma attacks in the last 6 months.

My blood test shows I have high eosinophils, or I have nasal polyps, or my lung function is reduced.

I've had fewer than 12 flare-ups of my condition in the last 6 months.

Exclusion Criteria

I haven't taken immunosuppressive drugs or received blood products in the last 30 days.

Currently pregnant, breastfeeding or lactating women.

I haven't had certain asthma treatments or vaccines recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive benralizumab or placebo subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks over a 48-week period

48 weeks

10 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Benralizumab

Trial Overview The trial is testing if benralizumab can improve lung structure and function over a 48-week period compared to a placebo in patients with severe eosinophilic asthma. Participants will be monitored for changes after treatment and during a four-week follow-up.

Participant Groups

Group I: Benralizumab Experimental Treatment 1 Intervention

Administrated subcutaneously (SC) every 4 weeks for the first 3 doses, then every 8 weeks

Group II: Placebo Placebo Group 1 Intervention

Administrated subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks

Benralizumab is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Fasenra for:

• Severe eosinophilic asthma

Approved in United States as Fasenra for:

• Severe asthma with an eosinophilic phenotype

Approved in Canada as Fasenra for:

• Severe eosinophilic asthma

Approved in Japan as Fasenra for:

• Severe eosinophilic asthma

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 a study of 441 patients with severe asthma, 19% were found to be eligible for benralizumab treatment, indicating a significant subset of patients who may benefit from this therapy.

Patients eligible for benralizumab had poorer lung function and asthma control, experiencing more frequent exacerbations and hospitalizations, highlighting the need for effective treatment options in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of patients with severe, uncontrolled, eosinophilic asthma enrolled in a French cohort. Aubier, M., Thabut, G., Fabry-Vendrand, C.[2022]

Benralizumab (Fasenra™) is a monoclonal antibody that targets the interleukin-5 receptor alpha chain, specifically designed to treat severe eosinophilic asthma and chronic obstructive pulmonary disease (COPD).

The drug has been approved by the US FDA as an add-on maintenance therapy for patients with severe asthma characterized by eosinophilia, highlighting its efficacy in depleting eosinophils, which are linked to asthma and COPD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benralizumab: First Global Approval. Markham, A.[2022]

Benralizumab is a monoclonal antibody that targets the interleukin-5 receptor, effectively inhibiting eosinophil and basophil proliferation, which is crucial for managing severe asthma.

Clinical trials have shown that benralizumab significantly reduces asthma exacerbation rates, improves lung function (measured by FEV1), and enhances quality of life for patients with high eosinophil counts, while being well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benralizumab for the treatment of asthma. Matera, MG., Rogliani, P., Calzetta, L., et al.[2018]

In a prospective study of 26 patients with severe asthma, benralizumab significantly improved asthma control and quality of life, as evidenced by increased scores on the asthma quality of life questionnaire and asthma control test after 12 weeks of treatment.

The treatment also led to a significant increase in lung function (FEV1) and a reduction in blood eosinophil counts, while showing a good safety profile with only one mild headache reported, indicating its potential effectiveness in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of benralizumab for severe asthma in clinical practice (J-BEST): a prospective study. Izumo, T., Tone, M., Kuse, N., et al.[2022]

In a study of 24 patients with severe type 2 asthma, benralizumab significantly reduced exacerbation rates and oral corticosteroid use after 24 weeks, with 76.2% of patients meeting the criteria for treatment response.

Baseline blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels were effective predictors of how well patients would respond to benralizumab, indicating that these biomarkers could help identify suitable candidates for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood eosinophil count and FeNO to predict benralizumab effectiveness in real-life severe asthma patients. Watanabe, H., Shirai, T., Hirai, K., et al.[2022]

In a Phase 1 study involving 36 healthy Chinese adults, a single subcutaneous injection of benralizumab was found to be well tolerated, with only mild adverse events reported, indicating a favorable safety profile.

Benralizumab effectively depleted eosinophils within 2 days of administration, and this effect was maintained for up to 85 days, demonstrating its potential efficacy in targeting eosinophilic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Pharmacokinetics of Benralizumab: A Phase 1, Randomized, Single-Blind Study of Healthy Chinese Participants. Cheung, TT., Mai, TH., Chia, YL., et al.[2023]

In a real-world study of 205 patients with severe eosinophilic asthma treated with benralizumab for an average of 9.8 months, there was a dramatic reduction in exacerbations, with 81% of patients becoming exacerbation-free and a 93.3% decrease in the annualized exacerbation rate.

Benralizumab treatment also led to significant reductions in oral corticosteroid use, with 43.2% of patients able to stop OCS therapy and an overall dose reduction of 56%, indicating its effectiveness in managing severe asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving Benralizumab in a real-life setting: the observational rEtrospective ANANKE study. Menzella, F., Bargagli, E., Aliani, M., et al.[2022]

Benralizumab effectively reduces asthma exacerbations, symptom burden, and the need for oral glucocorticoids while improving lung function in patients with severe eosinophilic asthma, highlighting its clinical efficacy.

The drug works by depleting eosinophils through its unique mechanism of action, which involves binding to the anti-IL5 receptor, and is well tolerated with a less frequent dosing schedule, making it a favorable option for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benralizumab: an updated treatment of eosinophilic asthma. Cushen, B., Menzies-Gow, A.[2021]

Benralizumab, a monoclonal antibody targeting the IL-5 receptor, led to complete histological remission of eosinophilic esophagitis (EoE) in a patient with severe asthma, demonstrating its potential as a treatment for eosinophil-associated diseases beyond asthma.

Despite achieving histological remission, the patient did not experience complete clinical remission, highlighting the complexity of EoE and the need for further research on the psychosomatic aspects and chronic nature of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histological remission of eosinophilic esophagitis under asthma therapy with IL-5 receptor monoclonal antibody: A case report. Huguenot, M., Bruhm, AC., Essig, M.[2022]

References

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

Characteristics of patients with severe, uncontrolled, eosinophilic asthma enrolled in a French cohort. [2022]

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

Benralizumab: First Global Approval. [2022]

3. Spain pubmed.ncbi.nlm.nih.gov

Benralizumab for the treatment of asthma. [2018]

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

Effectiveness and safety of benralizumab for severe asthma in clinical practice (J-BEST): a prospective study. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Blood eosinophil count and FeNO to predict benralizumab effectiveness in real-life severe asthma patients. [2022]

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

Safety, Tolerability, and Pharmacokinetics of Benralizumab: A Phase 1, Randomized, Single-Blind Study of Healthy Chinese Participants. [2023]

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

ChAracterization of ItaliaN severe uncontrolled Asthmatic patieNts Key features when receiving Benralizumab in a real-life setting: the observational rEtrospective ANANKE study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Benralizumab: an updated treatment of eosinophilic asthma. [2021]

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

Histological remission of eosinophilic esophagitis under asthma therapy with IL-5 receptor monoclonal antibody: A case report. [2022]