Benralizumab for Asthma

(CHINOOK Trial)

Not currently recruiting at 42 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called benralizumab (also known as Fasenra) to determine its effectiveness for people with severe eosinophilic asthma. In this type of asthma, high levels of certain white blood cells (eosinophils) cause breathing issues. Researchers aim to find out if benralizumab can improve lung function and reduce asthma symptoms for those who continue to struggle despite using inhalers and other medications. Participants will receive either benralizumab or a placebo (a dummy treatment) to compare the effects. This trial suits individuals who have had severe asthma for over a year and continue to experience symptoms despite regular inhaler use. As a Phase 4 trial, benralizumab is already FDA-approved and proven effective, and this research helps understand how it benefits more patients.

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 is the safety track record for Benralizumab?

Research has shown that benralizumab is generally safe for people with severe asthma. In clinical studies, participants taking benralizumab experienced side effects similar to those taking a placebo, which contains no active medicine. Specifically, about 76% of people on benralizumab reported side effects, compared to 80% on placebo, indicating that benralizumab's safety is comparable to not taking the active treatment.

Furthermore, benralizumab is an approved asthma treatment, underscoring its safety. This approval indicates thorough testing for safety and effectiveness. Long-term studies have shown that many patients using benralizumab did not experience asthma flare-ups, further demonstrating its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Benralizumab is unique because it specifically targets and depletes eosinophils, which are inflammatory cells that play a key role in certain types of asthma. Unlike many standard treatments for asthma, which mainly focus on bronchodilation or general inflammation reduction, benralizumab works by binding to the IL-5 receptor on eosinophils, leading to their destruction. Researchers are excited about this approach because it offers a more targeted treatment option, potentially providing better control of symptoms and reducing the need for corticosteroids, which can have significant side effects.

What is the effectiveness track record for benralizumab in treating severe eosinophilic asthma?

Research has shown that benralizumab, which participants in this trial may receive, effectively treats severe eosinophilic asthma, a type of asthma related to high levels of certain white blood cells. Studies indicate that 50% to 68% of patients experienced better asthma control with benralizumab. Additionally, 59% of patients did not experience any asthma flare-ups during a long-term study. Benralizumab also reduced asthma flare-ups in patients who had tried other treatments before. Overall, the evidence strongly supports its effectiveness in managing severe eosinophilic asthma. ^{1 2 3 6 7}

Who Is on the Research Team?

Mario Castro, MD

Principal Investigator

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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11844207/

Benralizumab Outcomes in Patients with Severe Eosinophilic ... Overall, the percentage of patients with asthma control (ACT>19) increased during benralizumab treatment, ranging from 50% to 68% at every ...

2. fasenrahcp.com fasenrahcp.com/long-term-data

Long-Term Data | FASENRA® (benralizumab) | For HCPs Of the patients receiving FASENRA Q8W, 59% had zero exacerbations across the extension study period (n=110; over 304 total follow-up years). The primary ...

3. resmedjournal.com resmedjournal.com/article/S0954-6111(23)00173-7/fulltext

Real-world effectiveness of benralizumab in US ... Benralizumab was associated with improved outcomes in severe eosinophilic asthma. Exacerbation reduction was observed in patients switching from other ...

4. jaci-inpractice.org jaci-inpractice.org/article/S2213-2198(23)00470-1/fulltext

Real-World Effectiveness Study of Benralizumab for ... Benralizumab reduced asthma exacerbation rates in patients with blood eosinophil counts less than 150, more than or equal to 150, 150 to less ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0954611124000854

Benralizumab efficacy and safety in severe asthma MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 ...

6. respiratory-research.biomedcentral.com respiratory-research.biomedcentral.com/articles/10.1186/s12931-023-02539-7

Achieving clinical outcomes with benralizumab in severe ... Almost half (43.7%) of the OP on benralizumab met all four criteria for clinical remission. Patients with concomitant CRSwNP obtained similar or ...

7. astrazeneca.com astrazeneca.com/media-centre/medical-releases/results-miracle-phase-iii-trial-show-treatment-fasenra-statistically-reduction-74-annual-exacerbation-rate-patients-asia-severe-eosinophilic-asthma.html

Results from the MIRACLE Phase III trial show treatment ... The MIRACLE Phase III trial investigated the efficacy and safety of benralizumab compared to placebo in 695 patients (aged 12 to 75 years) in ...