Benralizumab for Asthma

(DOMINICA Trial)

Recruiting at 74 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

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 evaluate its effectiveness and safety for children and teens with severe asthma that often flares up. Participants will receive either benralizumab or a placebo, both administered as injections under the skin. The trial targets individuals who have experienced severe asthma for at least a year, with frequent attacks despite high doses of inhaled steroids and other asthma medications. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for severe asthma.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that benralizumab is generally safe for people with severe asthma. In studies, about 76% of patients taking benralizumab reported side effects, similar to the 80% of patients who experienced side effects with a placebo (a non-active treatment). This suggests that benralizumab is well-tolerated. Additionally, long-term evidence indicates that many people using benralizumab experienced fewer asthma flare-ups over time. While side effects can occur with any treatment, these findings offer reassurance about the safety of benralizumab for treating severe asthma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for asthma?

Benralizumab is unique because it targets and depletes eosinophils, a type of white blood cell that plays a major role in asthma inflammation. Unlike standard treatments like corticosteroids that broadly suppress the immune system, benralizumab specifically targets the IL-5 receptor on eosinophils, potentially leading to fewer side effects. Researchers are excited about this targeted action, as it holds promise for a more tailored and effective treatment for asthma patients, particularly those with eosinophilic asthma.

What evidence suggests that benralizumab might be an effective treatment for severe eosinophilic asthma?

Research has shown that benralizumab, which participants in this trial may receive, effectively treats severe eosinophilic asthma, a type of asthma with high levels of eosinophils, a type of white blood cell. Studies have found that 50% to 68% of patients experienced better asthma control with benralizumab. Additionally, about 59% of patients did not have any asthma attacks over a long-term study period. Specifically, there was a significant decrease in asthma attacks within 48 weeks of starting treatment. These findings suggest that benralizumab can help manage symptoms and reduce flare-ups in patients with severe eosinophilic asthma. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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 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 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 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 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 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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10200058/

Long-term effectiveness of benralizumab in severe ... The results from the post hoc analysis conducted here show a dramatic reduction in any and severe AER at 48 weeks, with a further decrease ...

4. 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 ...

5. 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 ...

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

Benralizumab efficacy and safety in severe asthma The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. Conclusions. MIRACLE data reinforces the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10807277/

Real-World Safety and Effectiveness of Benralizumab in ... In total, 632 patients were evaluated for safety and 274 for effectiveness; 139 patients were included in the severe uncontrolled asthma ...