Benralizumab vs Mepolizumab for Vasculitis

(MANDARA Trial)

Recruiting at 67 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Corticosteroids

Must not be taking: Mepolizumab, Reslizumab

Disqualifiers: GPA, MPA, Malignancy, Cardiovascular, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

140 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of oral prednisolone or prednisone and, if applicable, stable immunosuppressive therapy (except cyclophosphamide) for at least 4 weeks before starting the trial and during the study. Some medications, like certain biologics and corticosteroids, must not have been taken recently before joining the trial.

What data supports the effectiveness of the drug Mepolizumab for vasculitis?

Research shows that Mepolizumab, when used for severe asthma, provides modest benefits, especially when other treatments do not fully control symptoms. This suggests it may help in conditions like vasculitis where inflammation is a problem. ^{1 2 3 4 5}

How do the drugs benralizumab and mepolizumab differ from other treatments for vasculitis?

Benralizumab and mepolizumab are unique because they target specific components of the immune system involved in inflammation, with benralizumab targeting the IL-5 receptor and mepolizumab targeting IL-5 itself. This approach is different from traditional treatments for vasculitis, which often rely on broad immunosuppressive drugs, and may offer more targeted relief for conditions like eosinophilic granulomatosis with polyangiitis (EGPA). ^{6 7 8 9 10}

What is the purpose of this trial?

This is a randomized, double blind, active-controlled, parallel group, multicenter 52-week Phase 3 study to compare the efficacy and safety of benralizumab 30 mg versus mepolizumab 300 mg administered by subcutaneous (SC) injection in patients with relapsing or refractory EGPA on corticosteroid therapy with or without stable immunosuppressive therapy. All patients who complete the 52-week double-blind treatment period on IP may be eligible to continue into an open label extension (OLE) period. The OLE period is intended to allow each patient at least 1 year of treatment with open-label benralizumab 30 mg administered SC (earlier enrolled patients may therefore be in the OLE for longer than 1 year).

Research Team

Michael Wechsler, MD

Principal Investigator

National Jewish Health, 1400 Jackson St Denver, CO 80206

Eligibility Criteria

Adults with relapsing or refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA) who are on stable corticosteroid and possibly immunosuppressive therapy, not pregnant, without recent malignancies or severe diseases that could interfere with the study. They must have a history of asthma and eosinophilia.

Inclusion Criteria

My EGPA has returned or didn't respond to treatment recently.

My dose of immunosuppressive medication has been stable.

Females of childbearing potential must use an acceptable method of birth control

Exclusion Criteria

I have or had cancer within the specified timeframes.

I am on long-term medication for an infection.

My liver condition is not stable.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either benralizumab 30 mg or mepolizumab 300 mg administered by subcutaneous injection for 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants may opt into continuation of treatment with open-label benralizumab 30 mg for at least 1 year

At least 1 year

Treatment Details

Interventions

• Benralizumab
• Mepolizumab

Trial Overview The trial is testing the effectiveness and safety of Benralizumab compared to Mepolizumab in treating EGPA. Both drugs are given by injection over a year, with an option for extended open-label treatment using Benralizumab.

Participant Groups

Group I: Benralizumab arm Experimental Treatment 2 Interventions

1x benralizumab SC injection + 3x placebo to mepolizumab SC injections

Group II: Mepolizumab arm Active Control 2 Interventions

3x mepolizumab SC injections + 1x placebo to benralizumab 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

Findings from Research

Dapirolizumab pegol (DZP) showed improvements in clinical and immunological outcomes for patients with moderately to severely active systemic lupus erythematosus (SLE) after 24 weeks, although the primary dose-response relationship was not statistically significant.

DZP was well tolerated with low incidences of serious adverse events, suggesting it is a safe option for SLE treatment, warranting further investigation into its clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2, randomized, placebo-controlled trial of dapirolizumab pegol in patients with moderate-to-severe active systemic lupus erythematosus. Furie, RA., Bruce, IN., Dörner, T., et al.[2022]

In a study of 10 prednisone-dependent asthma patients, weight-adjusted intravenous reslizumab significantly reduced sputum eosinophils by 91.2% and blood eosinophils by 87.4%, showing a strong efficacy compared to placebo.

Reslizumab also led to greater improvements in lung function (FEV1) and asthma control compared to the previously used mepolizumab, indicating it may be a more effective treatment option for managing eosinophilia in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight-adjusted Intravenous Reslizumab in Severe Asthma with Inadequate Response to Fixed-Dose Subcutaneous Mepolizumab. Mukherjee, M., Aleman Paramo, F., Kjarsgaard, M., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase 2, randomized, placebo-controlled trial of dapirolizumab pegol in patients with moderate-to-severe active systemic lupus erythematosus. [2022]

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

Safety and efficacy of brodalumab for psoriasis after 120 weeks of treatment. [2019]

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

Weight-adjusted Intravenous Reslizumab in Severe Asthma with Inadequate Response to Fixed-Dose Subcutaneous Mepolizumab. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The comparative efficacy of brodalumab in patients with moderate-to-severe psoriasis: a systematic literature review and network meta-analysis. [2019]

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

Long-term efficacy and safety of brodalumab in the treatment of psoriasis: 120-week results from the randomized, double-blind, placebo- and active comparator-controlled phase 3 AMAGINE-2 trial. [2020]

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

Effects of anti-IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real-life multicentre study (BIONIGE). [2022]

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

Targeting the IL-5 pathway in eosinophilic asthma: a comparison of mepolizumab to benralizumab in the reduction of peripheral eosinophil counts. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Benralizumab in Patients with Severe Eosinophilic Asthma: A Multicentre Real-Life Experience. [2023]

9. Japan pubmed.ncbi.nlm.nih.gov

Long-term Safety and Efficacy of Benralizumab for Eosinophilic Granulomatosis with Polyangiitis Complicated with Severe Neuropathy. [2023]

10. Japan pubmed.ncbi.nlm.nih.gov

[A CASE OF SEVERE ASTHMA SWITCHED TO MEPOLIZUMAB DUE TO LATE-OCCURRING UNRESPONSIVENESS TO BENRALIZUMAB]. [2020]