EosinophiliaPhase 2NCT04128371
Mepolizumab in Episodic Angioedema With Eosinophilia
A Phase 2 study testing mepolizumab in people with Eosinophilia and Angioedema, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Eosinophilia, Angioedema
- What is being tested?
- mepolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2021to 31 Oct 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A subject will be eligible for participation in the study only if all of the following criteria apply:
- The subject is male or female, aged 18 years or older.
- The subject has a documented diagnosis of EAE.
- The subject has symptoms of EAE in the cycle prior to screening, including but not limited to fever, swelling, hives or rashes, weight gain, muscle pain, and lymphadenopathy.
- Cycling of eosinophils is ongoing as indicated by a peak absolute eosinophil count (AEC) greater than or equal to 1500/mm^3 during at least one cycle in the prior 3 months.
- If taking corticosteroids, the subject is able and willing to stay on a stable dose for 6 weeks prior to screening.
Show all 24Show fewer
- The subject agrees to storage of study samples.
- The subject is able to provide informed consent.
- Females are eligible for this study if they are:
- of non-childbearing potential (i.e., women who have had a hysterectomy or tubal ligation or are postmenopausal as defined by no menses in 1 year); OR
- of childbearing potential but willing to practice effective contraception or abstinence during administration of the study drug and for 100 days (5 terminal half-lives) after administration of the study drug.
- Not breastfeeding.
- 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 reproductive potential 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:
- Diaphragm with spermicide
- Cervical cap with spermicide or contraceptive sponge (for nulliparous subjects only)
- Male or female condom (cannot be used together)
- Non-Barrier Methods
- An intrauterine device with a documented failure rate of <1%
- Hormonal contraception: pill (estrogen/progestin or progestin-only), patch, vaginal ring, rod implanted in the skin, or subcutaneous injection 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.
Who cannot join
- A subject will not be eligible to participate in the study if any of the following conditions are fulfilled at the time of screening:
- Treatment with immunosuppressive or immunomodulatory agents including but not limited to cyclosporine, interferon-alpha, azathioprine, methotrexate, and cyclophosphamide within the past 3 months.
- Treatment with biologics including but not limited to mepolizumab, IVIG, anti-TNF agents, rituximab, benralizumab, alemtuzumab, reslizumab, dupilumab, lebrikizumab, and omalizumab within 6 months or 5 half-lives (whichever is longer). Subjects who received rituximab at any time in the past must have normal B-cell numbers to participate.
- Co-morbid illness, alcohol or substance abuse, or any other condition (e.g., HIV, active hepatitis) that, in the opinion of the investigator, places the subject at undue risk by participating in the study.
- Treatment with a daily dose of corticosteroids >40 mg.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Pilot Study of Mepolizumab in Episodic Angioedema With Eosinophilia
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.
Read more
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.
Read the 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.
- Conditions
- Eosinophilia, Angioedema
- Being tested
- mepolizumab
- Keywords
- Absolute Neutrophil Count, Cycling, Gleich's Syndrome, Urticaria, Serum Interleukin 5
- Medical subject headings
- Eosinophilia, Angioedema, Urticaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mepolizumabBiological
Also called Nucala
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.
| Study group | Role | What they receive |
|---|---|---|
| Active treatment | Experimental | Participants with episodic angioedema with eosinophilia (EAE) received mepolizumab 700 mg intravenously monthly for three doses. Receives: Biological: mepolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 month prior to treatment and 3 months after treatment
Secondary outcomes (2)
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.
Measured: 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.
Measured: 1 month prior to treatment and 3 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2019
- Study start14 Jan 2021
- Primary completion31 Oct 2022
- Study completion31 Oct 2022
Why it stopped: Study was closed after the first five participants completed their participation due to lack of efficacy.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for EosinophiliaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Paneez Khoury, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04128371
- Sponsor's protocol ID
- 200002
- Other IDs
- 20-I-0002
- Status last verified
- Nov 2022
- First submitted
- 15 Oct 2019
- Last updated
- 16 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, Schwartz LB, Rosenwasser LJ, Ring J, Griffin EF, Haig AE, Frewer PI, Parkin JM, Gleich GJ; Mepolizumab HES Study Group. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008 Mar 20;358(12):1215-28. doi: 10.1056/NEJMoa070812. Epub 2008 Mar 16.
PubMed 18344568Gleich GJ, Schroeter AL, Marcoux JP, Sachs MI, O'Connell EJ, Kohler PF. Episodic angioedema associated with eosinophilia. N Engl J Med. 1984 Jun 21;310(25):1621-6. doi: 10.1056/NEJM198406213102501.
PubMed 6727934Khoury P, Herold J, Alpaugh A, Dinerman E, Holland-Thomas N, Stoddard J, Gurprasad S, Maric I, Simakova O, Schwartz LB, Fong J, Lee CC, Xi L, Wang Z, Raffeld M, Klion AD. Episodic angioedema with eosinophilia (Gleich syndrome) is a multilineage cell cycling disorder. Haematologica. 2015 Mar;100(3):300-7. doi: 10.3324/haematol.2013.091264. Epub 2014 Dec 19.
PubMed 25527564Khoury P, Makiya MA, Rahim R, Bowman A, Espinoza D, Schiffenbauer A, Koch M, Anderson C, Constantine G, Maric I, Sun X, Pittaluga S, Brown T, Ware JM, Wetzler L, Fay MP, Klion AD. Mepolizumab incompletely suppresses clinical flares in a pilot study of episodic angioedema with eosinophilia. J Allergy Clin Immunol. 2024 Mar;153(3):821-830.e6. doi: 10.1016/j.jaci.2023.11.002. Epub 2023 Nov 10.
PubMed 37951310
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Mepolizumab in Episodic Angioedema With Eosinophilia
- ClinicalTrials.gov ID
- NCT04128371
- Acronym / sponsor ID
- 200002
- Conditions
- Eosinophilia, Angioedema
- Keywords
- Absolute Neutrophil Count, Cycling, Gleich's Syndrome, Urticaria, Serum Interleukin 5
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was closed after the first five participants completed their participation due to lack of efficacy.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 14 Jan 2021 (actual)
- Primary completion
- 31 Oct 2022 (actual)
- Study completion
- 31 Oct 2022 (actual)
- First posted
- 16 Oct 2019 (actual)
- Results
- Posted 16 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Active treatment | Experimental | Biological: mepolizumabParticipants with episodic angioedema with eosinophilia (EAE) received mepolizumab 700 mg intravenously monthly for three doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- A subject will be eligible for participation in the study only if all of the following criteria apply:
- The subject is male or female, aged 18 years or older.
- The subject has a documented diagnosis of EAE.
- The subject has symptoms of EAE in the cycle prior to screening, including but not limited to fever, swelling, hives or rashes, weight gain, muscle pain, and lymphadenopathy.
- Cycling of eosinophils is ongoing as indicated by a peak absolute eosinophil count (AEC) greater than or equal to 1500/mm^3 during at least one cycle in the prior 3 months.
Key exclusion criteria (6 listed)
- A subject will not be eligible to participate in the study if any of the following conditions are fulfilled at the time of screening:
- Treatment with immunosuppressive or immunomodulatory agents including but not limited to cyclosporine, interferon-alpha, azathioprine, methotrexate, and cyclophosphamide within the past 3 months.
- Treatment with biologics including but not limited to mepolizumab, IVIG, anti-TNF agents, rituximab, benralizumab, alemtuzumab, reslizumab, dupilumab, lebrikizumab, and omalizumab within 6 months or 5 half-lives (whichever is longer). Subjects who received rituximab at any time in the past must have normal B-cell numbers to participate.
- Co-morbid illness, alcohol or substance abuse, or any other condition (e.g., HIV, active hepatitis) that, in the opinion of the investigator, places the subject at undue risk by participating in the study.
- Treatment with a daily dose of corticosteroids >40 mg.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mepolizumabAlso: NucalaMepolizumab 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. | Biological | Active treatment |
Primary outcome
Percent Change in Maximum Daily Angioedema Activity Score (AAS)
Time frame: 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.
2 secondary outcomes
Percent Change in Peak Absolute Eosinophil Count (AEC)
Time frame: 1 month prior to treatment and 1 month after treatment
Percent Change in Peak Absolute Eosinophil Count (AEC)
Time frame: 1 month prior to treatment and 3 months after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18344568Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, Schwartz LB, Rosenwasser LJ, Ring J, Griffin EF, Haig AE, Frewer PI, Parkin JM, Gleich GJ; Mepolizumab HES Study Group. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008 Mar 20;358(12):1215-28. doi: 10.1056/NEJMoa070812. Epub 2008 Mar 16.
- Background: PubMed 6727934Gleich GJ, Schroeter AL, Marcoux JP, Sachs MI, O'Connell EJ, Kohler PF. Episodic angioedema associated with eosinophilia. N Engl J Med. 1984 Jun 21;310(25):1621-6. doi: 10.1056/NEJM198406213102501.
- Background: PubMed 25527564Khoury P, Herold J, Alpaugh A, Dinerman E, Holland-Thomas N, Stoddard J, Gurprasad S, Maric I, Simakova O, Schwartz LB, Fong J, Lee CC, Xi L, Wang Z, Raffeld M, Klion AD. Episodic angioedema with eosinophilia (Gleich syndrome) is a multilineage cell cycling disorder. Haematologica. 2015 Mar;100(3):300-7. doi: 10.3324/haematol.2013.091264. Epub 2014 Dec 19.
- Results publication: PubMed 37951310Khoury P, Makiya MA, Rahim R, Bowman A, Espinoza D, Schiffenbauer A, Koch M, Anderson C, Constantine G, Maric I, Sun X, Pittaluga S, Brown T, Ware JM, Wetzler L, Fay MP, Klion AD. Mepolizumab incompletely suppresses clinical flares in a pilot study of episodic angioedema with eosinophilia. J Allergy Clin Immunol. 2024 Mar;153(3):821-830.e6. doi: 10.1016/j.jaci.2023.11.002. Epub 2023 Nov 10.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paneez Khoury, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing mepolizumab in people with Eosinophilia and Angioedema, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Maximum Daily Angioedema Activity Score (AAS) (time frame: 1 month prior to treatment and 3 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04128371, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2024.