AzTrials
AzTrials

Respiratory System AgentsPhase 2/3HESIL5RNCT02130882

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

A Phase 2/3 study testing benralizumab in people with Respiratory System Agents and Anti-Asthmatic Agents, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
benralizumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
1 siteUnited States
Study dates
19 May 2014to 31 Dec 2023
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • A subject will be eligible for participation in the study only if all of the following criteria apply:
  • Male or female subject greater than or equal to18 and less than or equal to 75 years of age at screening.
  • A female subject is eligible for this study only if she is not pregnant or breast-feeding and one of the following:
  • Of childbearing potential but agrees to practice effective contraception, as determined by the PI, or abstinence throughout the study and for 3 months after administration of the last dose of investigational study drug
  • Of non-child-bearing potential
  • Females of non-child-bearing potential are defined as females with functioning ovaries with a documented history of tubal ligation or hysterectomy or females who are post-menopausal, as defined by 12 months of spontaneous amenorrhea with an appropriate clinical profile, e.g. age appropriate, >45 years, in the absence of hormone replacement therapy. In questionable cases, a blood sample for follicle stimulating hormone and estradiol will be obtained to confirm child-bearing potential.
Show all 17Show fewer
  • Acceptable methods of contraception may include one or more of the following:
  • 1) male partner who is sterile prior to the female subject s entry into the study and is the sole sexual partner for the female subject; 2) implants of levonorgestrel; 3) injectable progestogen, 4) an intrauterine device with a documented failure rate of <1%; and 5) double barrier methods including diaphragm or condom with a spermicide.
  • 3) A male subject is eligible for this study only if he is one of the following:
  • Surgically sterile
  • Agrees to practice effective contraception (see above) or abstinence throughout the study and for 3 months after the last administration of the investigational study drug
  • 4) Documented diagnosis of HES (history of persistent eosinophilia >1500/(micro) L without secondary cause and evidence of end organ manifestations attributable to the eosinophilia)
  • 5) Signs or symptoms of HES and AEC >1000/(micro) L on stable HES therapy for greater than or equal to 1 month at the time of enrollment
  • 6) Participation in protocol 94-I-0079 (Activation and function of eosinophils in conditions with blood or tissue eosinophilia)
  • 7) Agrees to storage of samples for study
  • Participation of Women:
  • Contraception: The effects of benralizumab on the developing human fetus are unknown. For this reason, men and women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Females of childbearing-age must have a negative pregnancy test result prior to receiving benralizumab. During the course of the study, if a woman becomes pregnant or suspects she is pregnant, she should inform the study staff and her primary care physician immediately. If a subject becomes pregnant, the investigational drug will be discontinued immediately, and the subject will be counselled as to how to resume approved therapeutic options in consultation with an obstetric provider.

Who cannot join

  • A subject will be excluded from participation in the study if any of the following criteria apply at the time of enrollment:
  • Subjects with life-threatening or other serious illness or clinical manifestation of HES deemed inappropriate for inclusion in study per the principal investigator, including but not restricted to severe cardiac involvement and prior thromboembolic disease.
  • Human immunodeficiency virus (HIV) or other known immunodeficiency
  • Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Patients with a history of hepatitis B vaccination without history of hepatitis B are allowed to enroll
  • Presence of FIP1L1/PDGFRA or another known imatinib-sensitive mutation
  • Diagnosis of systemic mastocytosis or serum tryptase level >40 ng/mL
Show all 20Show fewer
  • Known lymphoma, hematological malignancy, advanced and metastatic solid tumors and/or subjects who are under chemotherapy, radiotherapy or interleukin 2 treatment
  • Known history of allergic or anaphylactic reaction to previous antibody therapy, including intravenous immunoglobulin and licensed or experimental monoclonal antibodies.
  • A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained
  • Acute bacterial or viral infection (subjects may be enrolled once the acute infection has resolved).
  • Receipt of intravenous immunoglobulin (IVIG) within 30 days prior to the date informed consent is obtained
  • Receipt of any marketed (eg omalizumab) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer
  • Receipt of live attenuated vaccines 30 days prior to the date of randomization
  • Receipt of inactive/killed vaccinations (e.g. inactive influenza) are allowed provided they are not administered within 1 week before/after any study visit
  • Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer
  • History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained
  • Previous treatment with benralizumab (MEDI-563).
  • Co-enrollment Guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies or those evaluating the use of a licensed medication. Study staff should be notified of co-enrollment as it may require the approval of the Investigator.
  • Justification for Exclusion of Children:
  • Because there are insufficient data regarding dosing or adverse events available in adults with HES to judge the potential risk in children, children are excluded from this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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)

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.
Read more

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.
Read the detailed description

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 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-5 receptor 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 absolute eosinophil count >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 a minimum of two years. Subjects with stable and complete response for greater than or equal to 2 years may be eligible to receive benralizumab at a dosing interval of every 8 weeks. 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-initiation 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, pharmacokinetics and anti-drug antibody (ADA) levels and eosinophil count after 24 weeks of every 8 week dosing. Exploratory endpoints will address predictors of response to benralizumab and the impact of eosinophil depletion on vaccine responses and glucose homeostasis. 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.

Being tested
benralizumab, Placebo
Keywords
Benralizumab, Pathologic Processes, Syndrome, Eosinophils, eosinophilic gastrointestinal disorders
Medical subject headings
Hematologic Diseases, Leukocyte Disorders, Eosinophilia, Pathologic Processes, Syndrome, Eosinophilic Esophagitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • benralizumabDrug

    An afucosylated humanized antibody to IL-5 receptor alpha

  • PlaceboOther

    A sterile solution containing 20 millimolar histidine/histidine-hydrochloride (HCl) 0.25 M trehalose dihydrate, and 0.006% (w/v) polysorbate 20, pH 6.0, in saline

Study groups in NCT02130882
Study groupRoleWhat they receive
DrugActive comparatorBenralizumab (30mg) will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background hypereosinophilic syndrome (HES) therapy will not be tapered.
Receives: Drug: benralizumab
PlaceboPlacebo comparatorPlacebo will be administered sc every 4 weeks for 3 doses (at weeks 0, 4 and 8). Eosinophil counts will be blinded during this time and background HES therapy will not be tapered.
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With 50% Reduction in Peripheral Blood Eosinophilia

    50% reduction in peripheral blood eosinophilia on stable HES background therapy at 12 weeks post-initiation of study drug

    Measured: 3 months

Secondary outcomes (1)

  1. Percent Reduction in Eosinophil Count

    Percent reduction in peripheral blood eosinophilia at 12 weeks post-treatment

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 May 2014 (estimated)
  2. Study start19 May 2014
  3. Primary completion1 Jun 2020
  4. Study completion31 Dec 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02130882
Sponsor's protocol ID
140081
Acronym
HESIL5R
Status last verified
9 Sep 2021
First submitted
3 Apr 2014
Last updated
8 Feb 2022
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 30943337

  • 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.

    PubMed 20513525

  • 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.

    PubMed 21762978

  • 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.

    PubMed 40120806

  • 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.

    PubMed 35283330

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing benralizumab in people with Respiratory System Agents and Anti-Asthmatic Agents, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 8 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With 50% Reduction in Peripheral Blood Eosinophilia (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02130882, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in