Mepolizumab in Episodic Angioedema With Eosinophilia
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|ClinicalTrials.gov Identifier: NCT04128371|
Recruitment Status : Recruiting
First Posted : October 16, 2019
Last Update Posted : May 20, 2021
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.
To see if mepolizumab causes EAE symptoms to be less severe and happen less often.
People ages 18 or older with EAE.
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.
|Condition or disease||Intervention/treatment||Phase|
|Eosinophilia Angioedema||Biological: Nucala (mepolizumab)||Phase 2|
Episodic angioedema with eosinophilia (EAE), also known as Gleich s Syndrome,is 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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of Mepolizumab in Episodic Angioedema With Eosinophilia|
|Actual Study Start Date :||January 14, 2021|
|Estimated Primary Completion Date :||March 31, 2022|
|Estimated Study Completion Date :||March 31, 2022|
Subjects will receive mepolizumab 700 mg IV x 3 doses at approximately one month intervals, at predicted eosinophil nadir (2-3 weeks after peak), at study visits 4, 6, and 7.
Biological: Nucala (mepolizumab)
Mepolizumab is a fully humanized monoclonal antibody (IgG1, kappa mAb) supplied as 100 mg of lyophilized powder in sterile, single-dose vials. Mepolizumab 100 mg vials will be reconstituted with 1.2 ml sterile water for injection (according to the product labeling) and secondarily diluted in 100-250 ml of 0.9% normal saline (NaCl) for infusion (to a final concentration of 0.3-7.5 mg/ml).
- Reduction in the number and severity of clinical symptoms associated with EAE after 3 doses of mepolizumab (as compared to symptoms logged in the approximately monthly cycle preceding initiation of mepolizumab). [ Time Frame: Visit 8 ]Reduction in the number and severity of clinical symptoms associated with EAE after 3 doses of mepolizumab (as compared to symptoms logged in the approximately monthly cycle preceding initiation of mepolizumab).
- Sustained reduction of eosinophilia after administration of mepolizumab (at Visit 8). [ Time Frame: Visit 8 ]
- A =75% reduction in peak blood eosinophil count following the first dose of mepolizumab (as compared to the peak eosinophil count in the cycle preceding initiation of mepolizumab therapy). [ Time Frame: Visits 3 and 4 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04128371
|Contact: Thomas W Brown, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Paneez Khoury, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|