A Phase 2 interventional study of mepolizumab in Eosinophilia and Angioedema, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-04-16.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 2, Interventional, and Treatment
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:
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.
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.
52 studies on the registry are indexed under Eosinophilia; 9 are open to participants now.
This study's enrollment of 5 is below the median of 48 across 32 interventional studies indexed under Eosinophilia.
Browse Eosinophilia studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
A subject will be eligible for participation in the study only if all of the following criteria apply:
Females are eligible for this study if they are:
Participation of Women:
Pregnancy: The effects of mepolizumab on the developing human fetus are unknown. For this reason, women of childbearing potential must agree to use adequate contraception (see below for acceptable methods) prior to study entry, for the duration of study participation, and for >5 terminal half-lives (approximately 100 days) after administration of the last dose of study drug. Nonreproductive potential is defined as post-menopausal, male partner who has azoospermia or is surgically sterile (at least 6 weeks before screening) and is the sole sexual partner, surgical sterility, or a congenital or acquired condition that definitely prevents conception. Further, postmenopausal is defined as at least 12 consecutive months with no menses at age 50 or older, or a high follicle-stimulating hormone level in the postmenopausal range at ages 45-50 years in subjects not using hormonal contraception or hormone replacement therapy.
Females with must either practice complete and uninterrupted abstinence from heterosexual activity or use 2 of the following methods of contraception with their partners. The 2 methods must include either 2 barrier methods, or 1 barrier method and 1 non-barrier method, both of which must be consistently used:
Barrier Methods:
Non-Barrier Methods
Females of childbearing-potential must have a negative pregnancy test result prior to receiving mepolizumab at each on-site study visit. During the course of the study, if a woman becomes pregnant or suspects she is pregnant, she should inform the study staff and her primary care physician immediately. A pregnancy registry has been created for subjects who become pregnant while receiving the approved dose of mepolizumab (100 mg subcutaneous injection) for asthma.
Fertility: There is no fertility data in humans. Animal studies showed no adverse effects of anti-IL-5 treatment on fertility.
EXCLUSION CRITERIA:
A subject will not be eligible to participate in the study if any of the following conditions are fulfilled at the time of screening:
Co-enrollment Guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies or those evaluating the use of a licensed medication. Study staff should be notified of co-enrollment as it may require the approval of the investigator.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants with episodic angioedema with eosinophilia (EAE) received mepolizumab 700 mg intravenously monthly for three doses.
Biological: 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 were reconstituted according to the manufacturer, for a total dose of 700mg administered as intravenous infusion.
Also known as: Nucala
Percent Change in Maximum Daily Angioedema Activity Score (AAS)
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.
Time frame: 1 month prior to treatment and 3 months after treatment
Percent Change in Peak Absolute Eosinophil Count (AEC)
Percent change in peak AEC is measured on each individual as the percentage change in peak AEC in the cycle following the first mepolizumab infusion 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.
Time frame: 1 month prior to treatment and 1 month after treatment
Percent Change in Peak Absolute Eosinophil Count (AEC)
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.
Time frame: 1 month prior to treatment and 3 months after treatment
| Milestone | Active Treatment |
|---|---|
| Started | 5 |
| Completed | 4 |
| Not completed | 1 |
| Withdrew: Lack of efficacy | 1 |
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.
| Percent change | Active Treatment |
|---|---|
| Percent Change in Maximum Daily Angioedema Activity Score (AAS) | 16.5 (-64.6 to 57.7) |
Percent change in peak AEC is measured on each individual as the percentage change in peak AEC in the cycle following the first mepolizumab infusion 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.
| Percent change | Active Treatment |
|---|---|
| Percent Change in Peak Absolute Eosinophil Count (AEC) | 82.2 (-108.5 to 98.5) |
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.
| Percent change | Active Treatment |
|---|---|
| Percent Change in Peak Absolute Eosinophil Count (AEC) | 96.2 (71.4 to 99.5) |
Collected over Up to 12 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Active Treatment | 0/5 (0%) | 0/5 (0%) | 4/5 (80%) |
| Event | Active Treatment |
|---|---|
| Coronavirus test positiveInvestigations | 2/5 |
| NauseaGastrointestinal disorders | 1/5 |
| Upper respiratory tract infectionInfections and infestations | 1/5 |
| Haemoglobin decreasedInvestigations | 1/5 |
| ParaesthesiaNervous system disorders | 1/5 |
| CoughRespiratory, thoracic and mediastinal disorders | 1/5 |
| PharyngitisRespiratory, thoracic and mediastinal disorders | 1/5 |
| Age, Categorical(Participants) | Active Treatment |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 5 |
| >=65 years | 0 |
| Sex: Female, Male(Participants) | Active Treatment |
|---|---|
| Female | 4 |
| Male | 1 |
| Ethnicity (NIH/OMB)(Participants) | Active Treatment |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 5 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Active Treatment |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 0 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 5 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Jan 2021 to primary completion in Oct 2022, 21 months.
Results were first posted in Apr 2024, 1 year 5 months after primary completion.
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This study is terminated, as verified in Nov 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Mepolizumab
National Institute of Allergy and Infectious Diseases (NIAID) →