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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 2a Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Subcutaneous Benralizumab (MEDI-563) in Reducing Eosinophilia in Subjects With 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

    Detailed Summary: Hypereosinophilic syndrome (HES) is a rare group of heterogeneous disorders characterized by marked peripheral eosinophilia (>1500/(micro)L) and evidence of eosinophil-associated tissue damage. Although a high proportion of patients respond initially to corticosteroid therapy, high doses are often necessary to control the eosinophilia and clinical symptoms, and many patients become relatively refractory to therapy and/or develop serious side effects. IL-5 receptor (alpha) (IL-5R (alpha) expression in humans is restricted to eosinophils, basophils, mast cells and their precursors and is, therefore, an ideal target for the therapy of HES. To date, there have been no safety concerns with benralizumab (anti-IL-5R(alpha)) in phase 1, 2 and 3 trials in asthma and efficacy data is promising. In order to explore the safety and efficacy of benralizumab in the treatment of HES, 20 adults (men and non-pregnant women, 18-75 years of age) with HES who are symptomatic with AEC >1000/(micro)L on stable HES therapy for at least 1 month will be recruited for this randomized, placebo-controlled, double-blind phase 2 trial. Benralizumab (30 mg) or placebo will be administered sc at weeks 0, 4, and 8. Eosinophil counts will be blinded for a subject and background HES therapy will not be tapered until that subject has been on study for 13 weeks. At weeks 12, 16, and 20, all subjects will receive a sc injection of benralizumab. Subjects demonstrating a response at the 24 week visit (eosinophil count <1000/(alpha) L and stable or improved clinical symptoms without an increase in background HES therapy) will continue to receive additional 30 mg sc injections every 4 weeks. Following the initial dose of benralizumab or placebo and the first open-label dose of benralizumab, subjects will be followed daily for 3 days, weekly for 4 weeks, and every 2 weeks for 8 weeks. Subsequent visits will be at 4 weeks intervals for responders and 12 weeks intervals for non-responders for the durat
    Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

    Current Primary Outcome: 50 percent reduction in peripheral blood eosinophilia on stable HES background therapy [ Time Frame: 12 weeks post-initiation of study drug ]

    Original Primary Outcome: Reduction of peripheral eosinophilia at 12 weeks [ Time Frame: 12 weeks ]

    Current Secondary Outcome:

    • Percent reduction in peripheral blood eosinophilia [ Time Frame: 12 weeks post-initiation of study drug ]
    • Frequency and severity of AEs [ Time Frame: Throughout study ]
    • Eosinophil count and background HES therapy at 1 year [ Time Frame: 1 year post-initiation of study drug ]


    Original Secondary Outcome:

    • Safety [ Time Frame: 12-48 weeks ]
    • Improvement in end organ manifestations, reduction of bone marrow eosinophils and mast cells [ Time Frame: 12-48 weeks ]
    • Long term efficacy, pharmacokinetics, development of antidrug antibodies [ Time Frame: 12-48 weeks ]


    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: April 3, 2014
    Date Started: March 13, 2014
    Date Completion: December 1, 2017
    Last Updated: April 20, 2017
    Last Verified: January 23, 2017