Study to Evaluate Safety and Efficacy of Benralizumab in Subjects With Hypereosinophilic Syndrome
- 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.
- To test if benralizumab can safely decrease eosinophils in people with HES.
- Adults age 18-65 who have been on stable HES therapy for at least 1 month but still have symptoms and high eosinophil levels.
- 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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|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 Hypereosinophilic Syndrome (HES)|
- 50 percent reduction in peripheral blood eosinophilia on stable HES background therapy [ Time Frame: 12 weeks post-initiation of study drug ] [ Designated as safety issue: No ]
- Percent reduction in peripheral blood eosinophilia [ Time Frame: 12 weeks post-initiation of study drug ] [ Designated as safety issue: No ]
- Frequency and severity of AEs [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
- Eosinophil count and background HES therapy at 1 year [ Time Frame: 1 year post-initiation of study drug ] [ Designated as safety issue: No ]
|Study Start Date:||March 2014|
|Estimated Study Completion Date:||March 2017|
|Estimated Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Monthly benralizumab (30 mg) administered as 1 mL sc
An afucosylated humanized antibody to IL-5 receptor alpha
Placebo Comparator: 2
Monthly placebo administered as 1 mL sc
A sterile solution containing 20 mM histidine/histidine-HCl, 0.25 M trehalose dihydrate, and 0.006% (w/v) polysorbate 20, pH 6.0, in saline
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 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 II trial. Benralizumab or placebo will be administered subcutaneously for 3 months, after which all subjects will receive benralizumab subcutaneously for 3 months. Eosinophil counts will be blinded for a subject and background 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 subcutaneous 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 duration of the study. Subjects will receive diphtheria-tetanus-acellular pertussis (TdaP) booster immunization at the 22 week visit. Titers will be measured 6 weeks after immunization.The primary endpoint of the study is a 50% reduction in peripheral blood eosinophilia on stable background therapy at 12 weeks post-inititation of study drug. Secondary endpoints will include absolute eosinophil count, the frequency and severity of adverse events, reduction in signs and symptoms of HES, tissue eosinophilia, numbers of eosinophils, mast cells and their precursors in bone marrow, levels of markers of eosinophil and mast cell activation, eosinophil count and background HES therapy at 1 year, and pharmacokinetics and anti-drug antibody (ADA) levels. Subjects who complete the study and for whom benralizumab provides sustained clinical benefit, may be eligible to receive drug on an open-label extension protocol until regulatory approval and commercial availability of the marketed drug to prescribing physicians (for any indication), or until development of benralizumab is discontinued by MedImmune.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02130882
|Contact: Tamika S Magee, R.N.||(301) email@example.com|
|Contact: Amy D Klion, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Amy D Klion, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|