Benralizumab for Eosinophilic Diseases

(CLIPS Trial)

Recruiting at 8 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Malignancy, Anaphylaxis history, System abnormalities, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

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

Compensation: Varies

Number of Visits: 4

Duration: 52 weeks

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests benralizumab to determine its safety and effectiveness for treating eosinophilic granulomatosis with polyangiitis (EGPA), a condition that inflames blood vessels and can affect organs. The study aims to assess the drug's efficacy and behavior in the body. Children and teens with EGPA who weigh more than 15 kilograms (about 33 pounds) and are on stable doses of corticosteroids or immunosuppressive therapy may qualify. Participants will receive benralizumab injections over 52 weeks, with an option to continue after completing the treatment period. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial requires that if you are on corticosteroids or immunosuppressive therapy, your dosage must be stable for at least 4 weeks before starting the trial. This means you should not change your current medication dose during that time.

Is there any evidence suggesting that benralizumab is likely to be safe for humans?

Research has shown that benralizumab is generally safe for people with eosinophilic granulomatosis with polyangiitis (EGPA). Studies have found that this treatment significantly improves many patients' conditions, often leading to remission, where symptoms greatly improve. Over two years, participants taking benralizumab experienced few relapses, suggesting the treatment's long-term effectiveness.

Regarding safety, benralizumab is well-tolerated, with most patients not experiencing severe side effects. While all treatments carry some risks, data indicate that serious issues are rare with benralizumab. This information may help prospective trial participants feel more at ease about the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Benralizumab is unique because it targets and depletes eosinophils, which are white blood cells that play a key role in eosinophilic diseases like Eosinophilic Granulomatosis with Polyangiitis (EGPA). While most treatments for EGPA, such as corticosteroids and immunosuppressants, broadly suppress the immune system, benralizumab specifically binds to the interleukin-5 receptor on eosinophils, leading to their destruction. This targeted approach not only aims to reduce the symptoms more effectively but also potentially minimizes the side effects associated with general immune suppression. Researchers are excited about benralizumab because it could offer a more precise and potentially safer alternative for managing EGPA.

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

Research has shown that benralizumab, the treatment under study in this trial, effectively treats eosinophilic diseases such as EGPA (Eosinophilic Granulomatosis with Polyangiitis). In earlier studies, 46% to 71% of patients experienced remission, with symptoms greatly reduced. Specifically, one study found a 59% remission rate at weeks 36 and 48 for those treated with benralizumab. This treatment also reduced the need for other medications, such as oral corticosteroids, and lowered eosinophil counts, a type of white blood cell involved in inflammation. Overall, benralizumab has shown promising results for patients with EGPA, making it a potential option for managing this condition. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for children with eosinophilic diseases such as Churg-Strauss Syndrome or Granulomatosis with Polyangiitis. Specific eligibility criteria are not provided, but typically participants must meet certain health conditions and cannot have factors that would exclude them from safely participating.

Inclusion Criteria

My body weight is at least 15 kg.

I am between 6 and 17 years old, and my caregiver has agreed to the study.

My steroid treatment for EGPA has been stable for at least 4 weeks.

Exclusion Criteria

My EGPA has relapsed within the last 3 months.

I have had a severe EGPA flare-up within the last 3 months.

All Cohorts: History of anaphylaxis to any biologic therapy or vaccine

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 to 4 weeks

Treatment

Participants receive benralizumab subcutaneous injections every 4 weeks

52 weeks

Visits every 4 weeks

Open-label extension

Participants may continue treatment for at least an additional year

At least 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Weeks after last investigational product administration

What Are the Treatments Tested in This Trial?

Interventions

• Benralizumab

Trial Overview The study is testing Benralizumab to see how safe it is for children, how well they tolerate it, and how their bodies process the drug (pharmacokinetics).

How Is the Trial Designed?

Group I: EGPA Cohort: Benralizumab Experimental Treatment 1 Intervention

Participants with greater than or equal to (\>=) 35 kg weight will receive benralizumab dose-1 and participants with less than (\<) 35 kg weight will receive benralizumab dose-2 as SC injection Q4W during the 52-week treatment period. All participants, who complete the 52-week treatment period, will be offered the opportunity to continue into an extension period.

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

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12584834/

Long-term effectiveness and safety of benralizumab in EGPA Benralizumab proved effective in achieving sustained remission, reducing OCS and immunosuppressant use, lowering blood eosinophil counts, and ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2213219825008293

Systematic Literature Review of Real-world Outcomes ... 46%–71% of patients from included cohorts experienced remission after benralizumab, with similar rates observed regardless of ANCA status, ...

3. astrazeneca.com astrazeneca.com/media-centre/medical-releases/mandara-phase-iii-data-published-new-england-journal-medicine-show-remission-achievable-goal-eosinophilic-granulomatosis-polyangiitis-egpa-fasenra.html

MANDARA Phase III data published in New England ... The primary endpoint of adjusted rate of remission was 59% for benralizumab-treated patients at weeks 36 and 48, compared with 56% for ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2311155

Benralizumab versus Mepolizumab for Eosinophilic ... Benralizumab was noninferior to mepolizumab for the induction of remission in patients with relapsing or refractory EGPA.

5. atsjournals.org atsjournals.org/doi/abs/10.1164/ajrccm.2025.211.Abstracts.A5029

Two-year Efficacy and Safety of Benralizumab in the ... In patients with EGPA receiving benralizumab, remission rates, OGC discontinuation, and bEOS depletion were durable over 104 weeks with low relapse rates.

6. jacionline.org jacionline.org/article/S0091-6749(24)02268-1/fulltext

Two-Year Efficacy and Safety of Benralizumab for the ... In patients with EGPA receiving benralizumab, remission rates, OGC discontinuation, and bEOS depletion are durable over 2 years, with low relapse rates.

7. ard.eular.org ard.eular.org/article/S0003-4967(25)04185-8/fulltext

Two-year efficacy and safety of anti-interleukin-5/receptor ... The anti-interleukin-5/receptor therapies mepolizumab and benralizumab are effective in inducing remission in some patients with EGPA. WHAT THIS ...