Benralizumab for Asthma

(DOMINICA Trial)

Recruiting at 68 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: High-dose ICS, Controller meds

Must not be taking: Immunosuppressives, Biologics

Disqualifiers: Pulmonary disease, Life-threatening asthma, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 15

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests benralizumab, an injectable medication, in children and teenagers aged 6 to 18 with severe eosinophilic asthma. The medication works by reducing specific white blood cells that cause lung inflammation, helping to control asthma symptoms. Benralizumab helps improve lung function for patients with severe, uncontrolled asthma with eosinophilic inflammation.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should be on stable asthma treatment with high-dose inhaled corticosteroids and at least one additional controller medication for at least 6 months before joining the study.

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

Research shows that Benralizumab helps reduce asthma attacks and improves symptoms and quality of life for people with severe eosinophilic asthma. It also decreases certain immune cells in the blood, which may help predict how well the drug will work for different patients. ^{1 2 3 4 5}

Is Benralizumab safe for humans?

Benralizumab has been studied for safety in healthy individuals and patients with severe asthma. It is generally considered safe, but like any medication, it may have side effects. Always consult with a healthcare provider for personalized advice. ^{4 5 6 7 8}

How is the drug Benralizumab different from other asthma treatments?

Benralizumab is unique because it is a monoclonal antibody (a type of protein made in the lab) that targets and depletes eosinophils, which are a type of white blood cell involved in inflammation in severe eosinophilic asthma. This drug is used as an add-on maintenance therapy for patients whose asthma is not well controlled with standard treatments like inhaled corticosteroids and long-acting beta-agonists. ^{4 6 7 8 9}

Eligibility Criteria

This trial is for children and teenagers aged 6 to under 18 with severe eosinophilic asthma. They must have a history of asthma exacerbations, be on high-dose inhaled corticosteroids plus another controller medication, and show certain levels of blood eosinophils. Females who can bear children must use effective contraception. Those with recent respiratory infections or steroid use, other significant health issues, or previous benralizumab treatment are excluded.

Inclusion Criteria

Patient and the caregiver (where applicable) must be willing to and be able to answer questionnaires that are part of the study procedures.

I have had severe asthma attacks needing steroids or hospital visits.

I can sign the consent form, and my caregiver can give consent for me.

Exclusion Criteria

You are allergic to benralizumab or any of the ingredients in the medication.

You have had a severe allergic reaction to any biologic medication in the past.

Previous randomisation in the present study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

8-12 weeks

Multiple visits as needed

Double-blind Treatment

Participants receive either benralizumab or placebo until an asthma exacerbation occurs or the required number of events is observed

Minimum 16 weeks

Visits at Day -7, Day 56, Day 112, and every 16 weeks

Open-label Extension

Participants who experience an asthma exacerbation receive benralizumab

48 weeks for ages 12-18, 104 weeks for ages 6-12

Regular visits throughout the period

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

End-of-treatment visit 8 weeks after last dose

Treatment Details

Interventions

• Benralizumab
• Placebo

Trial Overview The study tests the effectiveness and safety of benralizumab given by injection compared to a placebo in managing severe eosinophilic asthma in young patients. It focuses on reducing the number of asthma attacks (exacerbations) while monitoring any potential side effects from the treatment.

Participant Groups

Group I: Benralizumab Experimental Treatment 1 Intervention

Patients will receive Benralizumab as an active solution via a subcutaneous (SC) injection.

Group II: Placebo Placebo Group 1 Intervention

Patients will receive a matching solution of the placebo via SC injection.

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

Parexel

Industry Sponsor

Trials

322

Recruited

137,000+

Peyton Howell

Parexel

Chief Executive Officer

Master of Healthcare Administration from The Ohio State University, Bachelor of Arts in Health Communications from the University of Illinois

Dr. Austin Smith

Parexel

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

In a study of 36 patients with severe eosinophilic asthma, benralizumab treatment for one year significantly reduced exacerbations and improved symptoms, as measured by the ACT score and FEV1.

The study identified that changes in circulating Th17 cell frequencies and FeNO levels could serve as predictive biomarkers for determining the effectiveness of benralizumab treatment in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pretreatment Frequency of Circulating Th17 Cells and FeNO Levels Predicted the Real-World Response after 1 Year of Benralizumab Treatment in Patients with Severe Asthma. Sandhu, Y., Harada, N., Sasano, H., et al.[2023]

In a study of 64 patients with severe eosinophilic asthma treated with benralizumab for 4 months, significant improvements in lung function (FEV1) were observed, particularly in patients with higher levels of Type 2-related inflammatory markers.

The research identified five distinct phenotypes of severe eosinophilic asthma based on their response to benralizumab, suggesting that certain characteristics, like lower total IgE and FeNO levels, may predict better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of distinct phenotypes related to benralizumab responsiveness in patients with severe eosinophilic asthma. Yamada, H., Nakajima, M., Matsuyama, M., et al.[2021]

In a study of 18 patients with severe eosinophilic asthma, treatment with benralizumab led to a significant reduction in exacerbations from an average of 2.90 to 0.05 over 26 weeks, along with complete weaning off oral corticosteroids for all patients.

After 52 weeks, lung function improved markedly, with an average increase in FEV1 of 26.8%, and even greater improvements observed in patients with nasal polyposis and high blood eosinophil counts, indicating that benralizumab is a safe and effective treatment option for severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world effectiveness of benralizumab on respiratory function and asthma control. Menzella, F., Fontana, M., Galeone, C., et al.[2022]

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]

In the ANDHI study, 53.3% of non-oral corticosteroid (OCS)-dependent asthma patients were able to reduce their background medications after treatment with benralizumab, with this rate increasing to 72.6% for those who maintained asthma control.

For OCS-dependent patients, 50.5% were able to completely eliminate their OCS use, and 74.7% achieved a dosage of 5 mg or lower, indicating that benralizumab not only improves asthma control but also allows for significant reductions in corticosteroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy. Louis, R., Harrison, TW., Chanez, P., et al.[2023]

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 (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 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 429 patients with severe eosinophilic asthma treated with benralizumab, asthma exacerbation rates significantly decreased by 52% to 64% after treatment, demonstrating its effectiveness across various eosinophil levels.

Patients switching from other biologics to benralizumab also experienced substantial reductions in exacerbation rates, with 39% to 49% of patients having no exacerbations during the first 24 months of follow-up, indicating long-term clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Effectiveness Study of Benralizumab for Severe Eosinophilic Asthma: ZEPHYR 2. Carstens, D., Maselli, DJ., Mu, F., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Pretreatment Frequency of Circulating Th17 Cells and FeNO Levels Predicted the Real-World Response after 1 Year of Benralizumab Treatment in Patients with Severe Asthma. [2023]

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

Identification of distinct phenotypes related to benralizumab responsiveness in patients with severe eosinophilic asthma. [2021]

3. Italy pubmed.ncbi.nlm.nih.gov

Real world effectiveness of benralizumab on respiratory function and asthma control. [2022]

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

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

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

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Benralizumab: First Global Approval. [2022]

8. 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]

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

Real-World Effectiveness Study of Benralizumab for Severe Eosinophilic Asthma: ZEPHYR 2. [2023]