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

NCT02130882 | Unknown Phase 2 Results FDA Drug

• 1 other identifier: 140081
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Respiratory System Agents; Anti-Asthmatic Agents; Hematologic Diseases; Leukocyte Disorders; Hypereosinophilia

Keywords

Benralizumab; Pathologic Processes; Syndrome; Eosinophils; eosinophilic gastrointestinal disorders

Outcome Measures

Primary Outcomes (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

  3 months

Secondary Outcomes (1)

• Percent Reduction in Eosinophil Count

  3 months

Study Arms (2)

Drug

ACTIVE COMPARATOR

Benralizumab (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.

Drug: benralizumab

Placebo

PLACEBO COMPARATOR

Placebo 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.

Other: Placebo

Interventions

benralizumab DRUG

An afucosylated humanized antibody to IL-5 receptor alpha

Drug

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Acceptable methods of contraception may include one or more of the following:
• \) 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.
• \) 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
• \) Documented diagnosis of HES (history of persistent eosinophilia \>1500/(micro) L without secondary cause and evidence of end organ manifestations attributable to the eosinophilia)
• \) 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
• \) Participation in protocol 94-I-0079 (Activation and function of eosinophils in conditions with blood or tissue eosinophilia)
• \) Agrees to storage of samples for study

You may not qualify if:

• A subject will be excluded from participation in the study if any of the following criteria apply at the time of enrollment:
• 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
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• AstraZeneca: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 30943337 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.

  PMID: 20513525 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.

  PMID: 21762978 BACKGROUND

• 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.

  PMID: 35283330 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hematologic Diseases; Leukocyte Disorders; Eosinophilia; Pathologic Processes; Syndrome; Eosinophilic Esophagitis

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Pathological Conditions, Signs and Symptoms; Disease; Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Dr. Amy Klion
• Organization: National Institute of Allergy and Infectious Diseases, NIH

aklion@nih.gov

301-435-8903

Study Officials

• Amy D Klion, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2014
• First Posted: May 6, 2014
• Study Start: May 19, 2014
• Primary Completion: June 1, 2020
• Study Completion: December 31, 2023
• Last Updated: February 8, 2022
• Results First Posted: February 8, 2022

Record last verified: 2021-09-09

Locations

US (1)