Benralizumab vs Mepolizumab for Vasculitis
(MANDARA Trial)
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial compares two treatments, benralizumab (Fasenra, an injection) and mepolizumab (an injection), for individuals with Eosinophilic Granulomatosis with Polyangiitis (EGPA), a condition often involving asthma and elevated levels of certain white blood cells. The researchers aim to determine which treatment is more effective and safe for those whose EGPA symptoms persist or recur despite standard treatments. Individuals who have experienced EGPA flare-ups in the past two years and are on a stable dose of corticosteroids may qualify. Participants will receive one of the treatments through injections and may access an additional treatment phase upon completing the initial study period. As a Phase 3 trial, this study represents the final step before FDA approval, allowing participants to contribute to the potential availability of a new treatment option.
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.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
In a previous study, almost all patients taking benralizumab experienced some side effects, with serious ones occurring in about 23% of cases. Despite this, research has shown that benralizumab is generally safe for treating EGPA, a type of blood vessel inflammation. It also appears to help patients reach remission, meaning their disease symptoms lessen or disappear.
For mepolizumab, research suggests it is safe and effective in reducing the need for other medications like steroids. However, nearly all patients experienced some side effects, with about 38% facing serious ones. The most common issue was a reaction at the injection site.
Both treatments have proven effective in managing EGPA and are considered generally safe based on past studies.12345Why are researchers excited about this trial's treatments?
Unlike the standard treatments for vasculitis, which often include broad immunosuppressants, Benralizumab and Mepolizumab target specific components of the immune system. Benralizumab is unique because it targets the IL-5 receptor on eosinophils, leading to their rapid depletion, potentially reducing inflammation more directly and effectively. Mepolizumab, on the other hand, blocks IL-5 itself, which is also crucial in eosinophil survival and activity, offering a precise approach to managing eosinophil-driven inflammation. Researchers are excited about these treatments because they promise more targeted action with possibly fewer side effects compared to traditional therapies.
What evidence suggests that this trial's treatments could be effective for EGPA?
This trial will compare benralizumab and mepolizumab for treating eosinophilic granulomatosis with polyangiitis (EGPA), a type of blood vessel inflammation. Research has shown that benralizumab is promising, with about 59% of patients achieving remission and requiring fewer oral steroids. One study found that 67.1% of patients were in remission after one year of benralizumab treatment. Mepolizumab has also proven effective, with patients spending more time in remission compared to those on a placebo. Specifically, in one study, all patients achieved remission after about four months of mepolizumab treatment. Both treatments demonstrate effectiveness, each with strengths in helping patients achieve remission and reduce steroid use. Participants in this trial will receive either benralizumab or mepolizumab to evaluate their effectiveness in this condition.26789
Who Is on the Research Team?
Michael Wechsler, MD
Principal Investigator
National Jewish Health, 1400 Jackson St Denver, CO 80206
Are You a Good Fit for This Trial?
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
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive either benralizumab 30 mg or mepolizumab 300 mg administered by subcutaneous injection for 52 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
Open-label extension
Participants may opt into continuation of treatment with open-label benralizumab 30 mg for at least 1 year
What Are the Treatments Tested in This Trial?
Interventions
- Benralizumab
- Mepolizumab
Benralizumab is already approved in European Union, United States, Canada, Japan for the following indications:
- Severe eosinophilic asthma
- Severe asthma with an eosinophilic phenotype
- Severe eosinophilic asthma
- Severe eosinophilic asthma
Find a Clinic Near You
Who Is Running the Clinical Trial?
AstraZeneca
Lead Sponsor
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