Mepolizumab in Episodic Angioedema With Eosinophilia
- Conditions
- EosinophiliaAngioedema
- Interventions
- Biological: mepolizumab
- Registration Number
- NCT04128371
- 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 5
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Active treatment mepolizumab Participants with episodic angioedema with eosinophilia (EAE) received mepolizumab 700 mg intravenously monthly for three doses.
- Primary Outcome Measures
Name Time Method Percent Change in Maximum Daily Angioedema Activity Score (AAS) 1 month prior to treatment and 3 months after treatment We measure the number and severity of clinical symptoms associated with episodic angioedema with eosinophilia (EAE) using the maximum of the patient reported daily angioedema activity score, a validated patient reported outcome measure. The daily score was used to measure changes in swelling within a cycle. Participants answered 5 questions each day that were scored from 0-3 for each item. The daily score consisted of a minimum score of 0 and a maximum score of 15, the sum of the 5 question answers. Higher scores indicate a worse outcome. The change of the daily angioedema activity score is measured as the average percent reduction in the maximum score over the 3 cycles (about 3 months) after treatment compared to the cycle (about 1 month) pre-treatment. The estimated percent change and its confidence interval was calculated from a quasi-Poisson model. The model estimates a multiplicative treatment effect on the baseline AAS, and that effect is translated into a percent change.
- Secondary Outcome Measures
Name Time Method Percent Change in Peak Absolute Eosinophil Count (AEC) 1 month prior to treatment and 3 months after treatment Percent change in peak AEC is measured on each individual as the percentage change in peak AEC by visit 8 (3 months) compared to the peak AEC in the cycle prior to mepolizumab treatment. Those values are summarized by taking the mean of a transformation of each percent change in peak AEC, and back-transforming the results. Specifically, if x is the percent change in peak AEC, then the transformation is log(1-x/100). The estimated percent change and its confidence interval was calculated using the mean of the transformed values and using the associated one-sample t-test confidence interval on that mean, then translating those estimates and confidence intervals back to the percent change scale.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States