Mepolizumab in Episodic Angioedema With Eosinophilia

NCT04128371 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 20000220-I-0002
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

Eosinophilia; Angioedema

Keywords

Absolute Neutrophil Count; Cycling; Gleich's Syndrome; Urticaria; Serum Interleukin 5

Outcome Measures

Primary Outcomes (1)

• 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.

  1 month prior to treatment and 3 months after treatment

Secondary Outcomes (2)

• Percent Change in Peak Absolute Eosinophil Count (AEC)

  1 month prior to treatment and 1 month after treatment

• Percent Change in Peak Absolute Eosinophil Count (AEC)

  1 month prior to treatment and 3 months after treatment

Study Arms (1)

Active treatment

EXPERIMENTAL

Participants with episodic angioedema with eosinophilia (EAE) received mepolizumab 700 mg intravenously monthly for three doses.

Biological: mepolizumab

Interventions

mepolizumab BIOLOGICAL

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

Active treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 18344568 BACKGROUND

• Gleich 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.

  PMID: 6727934 BACKGROUND

• Khoury 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.

  PMID: 25527564 BACKGROUND

• Khoury 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.

  PMID: 37951310 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Eosinophilia; Angioedema; Urticaria

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Diseases; Cardiovascular Diseases; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Limitations and Caveats

Study was closed due to futility

Results Point of Contact

• Title: Dr. Paneez Khoury
• Organization: National Institute of Allergy and Infectious Diseases

paneez.khoury@nih.gov

+1 301 402 3673

Study Officials

• Paneez Khoury, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2019
• First Posted: October 16, 2019
• Study Start: January 14, 2021
• Primary Completion: October 31, 2022
• Study Completion: October 31, 2022
• Last Updated: April 16, 2024
• Results First Posted: April 16, 2024

Record last verified: 2022-11

Locations

US (1)