Ignite Creation Date:
2024-05-06 @ 1:47 PM
Last Modification Date:
2024-10-26 @ 1:20 PM
Study NCT ID:
NCT04128371
Status:
TERMINATED
Last Update Posted:
2024-04-16
First Post:
2019-10-15
Brief Title:
Mepolizumab in Episodic Angioedema With Eosinophilia
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Pilot Study of Mepolizumab in Episodic Angioedema With Eosinophilia
Status:
TERMINATED
Status Verified Date:
2022-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Study was closed after the first five participants completed their participation due to lack of efficacy
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Gleich syndrome is also called episodic angioedema with eosinophilia EAE People with EAE have episodes of swelling They may also have itching hives fever and weight gain During episodes the body has very high numbers of white blood cells especially a kind called eosinophils Researchers think a drug called mepolizumab could help
Objective
To see if mepolizumab causes EAE symptoms to be less severe and happen less often
Eligibility
People ages 18 or older with EAE
Design
Participants will be screened under NIH protocol 94-I-0079
Participants will have 8 visits over about 6 months The timing of some visits will depend on each participant s EAE episodes Visits will include
Medical history
Physical exam
Blood and urine tests
Optional bone marrow collection at first or second visit For this a needle will be inserted through the participant s hip bone into the marrow
Participants will get mepolizumab 3 times over about 3 months They will get their first dose when their eosinophils are at their lowest point They will get the drug by IV A needle will guide a thin plastic tube into an arm vein The drug will be given through the tube over about 30 minutes
Participants will keep a daily online log for about 3 months The log will track their weight temperature and EAE symptoms During the whole study they will complete 2 online questionnaires about their symptoms They will fill out 1 daily and 1 monthly
Participants will have blood and urine tests 2-3 times a week For these they will go to their local doctor
Gleich syndrome is also called episodic angioedema with eosinophilia EAE People with EAE have episodes of swelling They may also have itching hives fever and weight gain During episodes the body has very high numbers of white blood cells especially a kind called eosinophils Researchers think a drug called mepolizumab could help
Objective
To see if mepolizumab causes EAE symptoms to be less severe and happen less often
Eligibility
People ages 18 or older with EAE
Design
Participants will be screened under NIH protocol 94-I-0079
Participants will have 8 visits over about 6 months The timing of some visits will depend on each participant s EAE episodes Visits will include
Medical history
Physical exam
Blood and urine tests
Optional bone marrow collection at first or second visit For this a needle will be inserted through the participant s hip bone into the marrow
Participants will get mepolizumab 3 times over about 3 months They will get their first dose when their eosinophils are at their lowest point They will get the drug by IV A needle will guide a thin plastic tube into an arm vein The drug will be given through the tube over about 30 minutes
Participants will keep a daily online log for about 3 months The log will track their weight temperature and EAE symptoms During the whole study they will complete 2 online questionnaires about their symptoms They will fill out 1 daily and 1 monthly
Participants will have blood and urine tests 2-3 times a week For these they will go to their local doctor
Detailed Description:
Episodic angioedema with eosinophilia EAE also known as Gleich s Syndromeis a rare disorder characterized by recurrent episodes of urticaria fever angioedema weight gain and dramatic eosinophilia that occur at 3- to 6-week intervals and resolve with spontaneous diuresis in the absence of therapy Although the syndrome is often classified in the broad category of idiopathic hypereosinophilic syndrome HES EAE is a distinct eosinophilic syndrome that is remarkably homogeneous in clinical presentation More recently it has become apparent that there is multilineage cycling involving lymphocytes and neutrophils in addition to eosinophils Early studies described cyclic elevations of serum interleukin 5 IL-5 preceding the rise in eosinophilia and additional studies have shown cyclic elevations in other type II cytokines as well as in eosinophilic chemokines Aberrant T cells with a CD3-CD4 surface phenotype have also been detected in the majority of subjects with EAE The cyclic nature of the disorder and the involvement of multiple cell lineages have made it difficult to determine the underlying cause of EAE
We hypothesize that IL-5 driven eosinophilia is central to the pathogenesis of EAE Suppression of eosinophil cycling by blocking IL-5 would help determine whether eosinophils are indeed the main drivers of the symptoms of angioedema and urticaria and pave the way for future mechanistic studies investigating the etiology of this unusual disorder The purpose of this pilot study is to evaluate the effect of mepolizumab a humanized antibody to IL-5 on eosinophil cycling in 12 subjects with EAE Subjects with EAE will undergo screening on the National Institutes of Health protocol 94-I-0079 to establish the periodicity of their cycling if not previously determined and the optimal timing for the baseline visit After screening subjects will be followed closely with signs and symptoms recorded in a daily log and daily and monthly questionnaires as well as complete blood counts and research blood collected for one cycle prior to administration of mepolizumab Subjects will receive a total of 3 monthly administrations of mepolizumab at 700 mg followed by drug de-escalation over 6 additional monthly administrations for subjects who demonstrate benefit from mepolizumab All subjects will have a follow-up visit about 1 month after the last study administration of mepolizumab
The primary efficacy endpoint will be reduction of symptoms and severity of symptoms after mepolizumab Secondary endpoints will include reduction in peak eosinophils after mepolizumab continued suppression of absolute eosinophil count and reduction in symptoms following monthly dosing of mepolizumab therapy
We hypothesize that IL-5 driven eosinophilia is central to the pathogenesis of EAE Suppression of eosinophil cycling by blocking IL-5 would help determine whether eosinophils are indeed the main drivers of the symptoms of angioedema and urticaria and pave the way for future mechanistic studies investigating the etiology of this unusual disorder The purpose of this pilot study is to evaluate the effect of mepolizumab a humanized antibody to IL-5 on eosinophil cycling in 12 subjects with EAE Subjects with EAE will undergo screening on the National Institutes of Health protocol 94-I-0079 to establish the periodicity of their cycling if not previously determined and the optimal timing for the baseline visit After screening subjects will be followed closely with signs and symptoms recorded in a daily log and daily and monthly questionnaires as well as complete blood counts and research blood collected for one cycle prior to administration of mepolizumab Subjects will receive a total of 3 monthly administrations of mepolizumab at 700 mg followed by drug de-escalation over 6 additional monthly administrations for subjects who demonstrate benefit from mepolizumab All subjects will have a follow-up visit about 1 month after the last study administration of mepolizumab
The primary efficacy endpoint will be reduction of symptoms and severity of symptoms after mepolizumab Secondary endpoints will include reduction in peak eosinophils after mepolizumab continued suppression of absolute eosinophil count and reduction in symptoms following monthly dosing of mepolizumab therapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 20-I-0002 | None | None | None |