Study to Evaluate Safety and Efficacy of Benralizumab in Subjects With Hypereosinophilic Syndrome

Summary

Background: \- Eosinophils are white blood cells that help fight infections. High eosinophil levels can damage people s organs, causing hypereosinophilic syndrome (HES). Researchers want to study if the drug benralizumab can help people with HES. Objective: \- To test if benralizumab can safely decrease eosinophils in people with HES. Eligibility: \- Adults age 18-65 who have been on stable HES therapy for at least 1 month but still have symptoms and high eosinophil levels. Design: * Participants will be screened with medical history, physical exam, and urine and blood tests. They will take simple heart and lung tests. * Participants will also have a bone marrow biopsy. A numbing medicine is injected into the outer covering of the bone. Then a needle is inserted into the bone. A fast suction movement takes bone marrow cells. * Phase 1: Participants will randomly receive either the study drug or placebo as an injection. * They will have daily visits for the next 3 days, then 4 weekly visits, and then 4 biweekly visits. Each time, they will have medical history, physical exam, blood tests, and a check of side effects. * They will receive another dose of the study drug or placebo at 1 month and 2 months after the first injection. * Phase 2 repeats the Phase 1 schedule. All participants will receive the study drug. * At 1 visit, participants will also receive a vaccine. At 4 visits, they will repeat the heart and lung tests. They will also have one other bone marrow biopsy. * After week 24, participants will receive the study drug either 6 times over 6 months or twice over 6 months.

Timeline

Start

2014-05-19

Primary completion

2020-06-01

Completion

2023-12-31

Publications

• Background Kuang FL, Legrand F, Makiya M, Ware J, Wetzler L, Brown T, Magee T, Piligian B, Yoon P, Ellis JH, Sun X, Panch SR, Powers A, Alao H, Kumar S, Quezado M, Yan L, Lee N, Kolbeck R, Newbold P, Goldman M, Fay MP, Khoury P, Maric I, Klion AD. Benralizumab for PDGFRA-Negative Hypereosinophilic Syndrome. N Engl J Med. 2019 Apr 4;380(14):1336-1346. doi: 10.1056/NEJMoa1812185.
• Background Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, Reed JL, Woods R, Dall'acqua WW, Stephens GL, Erjefalt JS, Bjermer L, Humbles AA, Gossage D, Wu H, Kiener PA, Spitalny GL, Mackay CR, Molfino NA, Coyle AJ. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010 Jun;125(6):1344-1353.e2. doi: 10.1016/j.jaci.2010.04.004.
• Background Wilson TM, Maric I, Shukla J, Brown M, Santos C, Simakova O, Khoury P, Fay MP, Kozhich A, Kolbeck R, Metcalfe DD, Klion AD. IL-5 receptor alpha levels in patients with marked eosinophilia or mastocytosis. J Allergy Clin Immunol. 2011 Nov;128(5):1086-92.e1-3. doi: 10.1016/j.jaci.2011.05.032. Epub 2011 Jul 16.
• Kuang FL, Makiya MA, Ware JM, Wetzler L, Nelson C, Brown T, Khoury P, Klion AD. Long-Term Efficacy and Safety of Benralizumab Treatment for PDGFRA-Negative Hypereosinophilic Syndrome. J Allergy Clin Immunol Pract. 2025 Jun;13(6):1421-1429.e2. doi: 10.1016/j.jaip.2025.03.016. Epub 2025 Mar 20.
• Kuang FL, De Melo MS, Makiya M, Kumar S, Brown T, Wetzler L, Ware JM, Khoury P, Collins MH, Quezado M, Pittaluga S, Klion AD. Benralizumab Completely Depletes Gastrointestinal Tissue Eosinophils and Improves Symptoms in Eosinophilic Gastrointestinal Disease. J Allergy Clin Immunol Pract. 2022 Jun;10(6):1598-1605.e2. doi: 10.1016/j.jaip.2022.02.037. Epub 2022 Mar 10.

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Indications