Steroid Treatment for Hypereosinophilic Syndrome

NCT01524536 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 12002612-I-0026
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Hypereosinophilic syndrome (HES) is a disorder in which the body has too many eosinophils (a type of white blood cell). Too many eosinophils in HES can cause damage to the heart, nerves, or skin. Certain drugs can help lower eosinophil counts to prevent tissue damage. Corticosteroids, such as prednisone, are used for initial therapy in this disorder. Although most people respond to prednisone, some people develop side effects from it, or do not respond very well to treatment. Better ways of determining the dose to give could help to decide on the best therapy for HES. Objectives:

• To determine whether a single-dose of prednisone can be used to predict which people with hypereosinophilia respond to treatment.
• To study lack of response to steroid treatment in people with HES. Eligibility: Inclusion criteria:
• Individuals with hypereosinophilic syndrome with high eosinophil counts.
• Individuals who are willing to have blood drawn before and after getting steroids. Exclusion criteria:
• Individuals who are on more than 10mg of prednisone (or similar drug)
• Individuals with hypereosinophilic syndrome who are on other medications that could interfere with the study
• Women who are pregnant or breast-feeding
• Individuals who have a known gene mutation associated with chronic eosinophilic leukemia
• Children less than 18 years old who weigh less than 48kg or 106lb Design:
• Participants will have a screening visit with a physical exam and medical history. Blood and urine samples will be collected.
• Participants will have a single dose of the steroid prednisone by mouth in the morning. Blood samples will be collected 2, 4, 24 hours after this dose.
• On the day after the steroid dose, participants will provide another blood sample in the morning.
• Participants will start to take prednisone daily when they return home. Blood samples will be collected weekly at the participant s doctor s office. The dose of prednisone will be lowered depending on the weekly eosinophil count. We will try to get each person on the lowest dose of prednisone possible that will control the disorder. Participants who do not respond or have severe side effects will be taken off prednisone. Other treatments will be considered for people who do not respond to steroids. The goal is to evaluate the response to prednisone. Our research will try to figure out why some people do not respond to steroids. Most people will complete the study within 6 to 16 weeks, depending on their response to prednisone.

Conditions

Eosinophilia; Hypereosinophilic Syndrome; Leukocyte Disorder; Hematologic Diseases

Keywords

Hypereosinophilia; Hypereosinophilic Syndrome; Corticosteroids; Therapy; HES

Outcome Measures

Primary Outcomes (1)

• Mean Percent Change in Eosinophil Count After Glucocorticoid Challenge

  Response to glucocorticoid challenge as assessed by the percentage of the eosinophil count 24 hours post-glucocorticoid challenge relative to the Baseline AEC for each participant. Measure Description (%): Percent of baseline AEC is defined as the Absolute Eosinophil Count at 24 hours divided by the Absolute Eosinophil Count at Baseline \*100.

  24 hours

Secondary Outcomes (8)

• Participants With Glucocorticoid Responsiveness - IHES Variant

  Baseline (Day 1)

• Participants With Glucocorticoid Responsiveness - LHES Variant

  Baseline (Day 1)

• Participants With Glucocorticoid Responsiveness - MHES Variant

  Baseline (Day 1)

• Participants With Glucocorticoid Responsiveness - Overlap HES Subtypes

  Baseline (Day 1)

• Mean Baseline IgE Level

  Baseline (Day 1)

Study Arms (1)

Steroid Challenge

OTHER

A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) was administered to all participants. The following day, participant began glucocorticoid therapy of prednisone 30 mg oral daily for one week followed by a standardized taper until a minimally effective dose was achieved or participant tapered to prednisone 5 mg oral daily.

Drug: prednisone

Interventions

prednisone DRUG

Glucocorticoids (GC) are considered the first- line therapy for hypereosinophilic syndrome.

Steroid Challenge

Eligibility Criteria

• Age: 7 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects on Protocol #94-I-0079 will be eligible for participation in the study only if all of the following criteria apply:
• Subjects must be 7 years of age or older to enroll
• Subject meets diagnostic criteria for HES (AEC \>1500/microL, absence of a secondary cause and signs and/or symptoms attributable to the eosinophilia)
• AEC greater than 1500 microL obtained within 14 days prior to enrollment
• Willingness to perform the timed steroid challenge
• Appropriate candidate for GC treatment after challenge
• Willingness to have samples stored for future research

You may not qualify if:

• A subject will not be eligible to participate in the study if any of the following apply:
• Receiving \>10 mg prednisone or equivalent at the time of enrollment.
• Receiving less than or equal to 10 mg of prednisone or equivalent but have not been on a fixed dose for at least 3 weeks (subjects on a current corticosteroid taper will be excluded).
• AEC less than or equal to 1500/microl on the day of the steroid challenge
• Use of immunomodulatory medications, (other than less than or equal to 10 mg/day prednisone) including but not limited to biologics, within the past 6 months.
• Pregnant at the time of screening.
• Have a known mutation in the FIP1L1-PDGFR gene.
• Any condition that, in the opinion of the investigator, places the subject at undue risk by participating in the protocol.
• Weight less than 48 kg (106 lbs) in subjects less than 18 years of age.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, Leiferman KM, Nutman TB, Pfab F, Ring J, Rothenberg ME, Roufosse F, Sajous MH, Sheikh J, Simon D, Simon HU, Stein ML, Wardlaw A, Weller PF, Klion AD. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 2009 Dec;124(6):1319-25.e3. doi: 10.1016/j.jaci.2009.09.022.

  PMID: 19910029 BACKGROUND

• Prin L, Lefebvre P, Gruart V, Capron M, Storme L, Formstecher P, Loiseau S, Capron A. Heterogeneity of human eosinophil glucocorticoid receptor expression in hypereosinophilic patients: absence of detectable receptor correlates with resistance to corticotherapy. Clin Exp Immunol. 1989 Dec;78(3):383-9.

  PMID: 2612051 BACKGROUND

• Hamilos DL, Leung DY, Muro S, Kahn AM, Hamilos SS, Thawley SE, Hamid QA. GRbeta expression in nasal polyp inflammatory cells and its relationship to the anti-inflammatory effects of intranasal fluticasone. J Allergy Clin Immunol. 2001 Jul;108(1):59-68. doi: 10.1067/mai.2001.116428.

  PMID: 11447383 BACKGROUND

• Stokes K, Yoon P, Makiya M, Gebreegziabher M, Holland-Thomas N, Ware J, Wetzler L, Khoury P, Klion AD. Mechanisms of glucocorticoid resistance in hypereosinophilic syndromes. Clin Exp Allergy. 2019 Dec;49(12):1598-1604. doi: 10.1111/cea.13509. Epub 2019 Oct 27.

  PMID: 31657082 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Eosinophilia; Hypereosinophilic Syndrome; Leukocyte Disorders; Hematologic Diseases

Interventions

Prednisone

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Paneez Khoury
• Organization: National Institute of Allergy and Infectious Diseases

khouryp@niaid.nih.gov

+1 301 402 3773

Study Officials

• Paneez Khoury, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2012
• First Posted: February 2, 2012
• Study Start: February 16, 2012
• Primary Completion: December 10, 2020
• Study Completion: December 10, 2020
• Last Updated: February 15, 2022
• Results First Posted: February 15, 2022

Record last verified: 2021-02-22

Locations

US (1)