Mepo for Eosinophilic Esophagitis (EoE) Study

NCT03656380 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 18-0431
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 4

Brief Summary

Multi-center, randomized, double blind, parallel-arm, placebo controlled trial to determine whether mepolizumab is more effective than placebo for improving symptoms of dysphagia and decreasing esophageal eosinophil counts in adults and adolescents with active eosinophilic esophagitis (EoE) after an initial 3 month treatment course, and will also assess the impact of an additional 3 months of treatment.

Conditions

EoE; Eosinophilic Esophagitis

Outcome Measures

Primary Outcomes (1)

• Mean Change in Dysphagia Score

  Dysphagia will be assessed by the Eosinophilic Esophagitis Symptom Activity Index (EEsAI) which measures dysphagia frequency, dysphagia severity, and food avoidance/modification behaviors. EEsAI scores range from 0 to 100, with higher scores indicating more severe symptoms. A decrease of ≥ 20 points is felt to be a meaningful clinical response and scores ≤ 20 representing clinical remission.

  Baseline, Month 3 Post-Treatment

Secondary Outcomes (6)

• Percent of Participants With a Clinical Remission (EEsAI Score of ≤ 20 Points)

  After 3 months of treatment

• Percent of Participants With a Clinical Response (EEsAI Score Decrease of ≥ 20 Points)

  After 3 months of treatment

• Absolute Peak Eosinophil Count

  After 3 months of treatment

• Number of Participants With Histologic Response as Assessed by Eosinophils Per High Powered Field

  After 3 months of treatment

• Mean Change in Eosinophilic Esophagitis Endoscopic Reference Score (EREFS)

  Baseline, 3 months post-treatment

Study Arms (2)

Mepolizumab 300 mg

EXPERIMENTAL

Subjects will receive Mepolizumab 300 mg subcutaneously (SQ) monthly for 6 months

Drug: Mepolizumab 300 mg

Placebo, followed by Mepolizumab 100 mg

OTHER

This arm will receive placebo, followed by Mepolizumab 100 mg. Subjects will receive placebo subcutaneously (SQ) monthly for 3 months, followed by Mepolizumab 100 mg subcutaneously (SQ) monthly for 3 months. Mepolizumab will be administered with 2 SQ injections of placebo and 1 SQ injection of Mepolizumab 100 mg to maintain blinding.

Drug: Mepolizumab 100 mg; Other: Placebo

Interventions

Mepolizumab 300 mg DRUG

Mepolizumab 300 mg subcutaneous injection

Also known as: Nucala

Mepolizumab 300 mg

Mepolizumab 100 mg DRUG

Mepolizumab 100 mg subcutaneous injection

Also known as: Nucala

Placebo, followed by Mepolizumab 100 mg

Placebo OTHER

Saline subcutaneous injection

Also known as: Saline

Placebo, followed by Mepolizumab 100 mg

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 16-75
• Diagnosis of EoE (eosinophilic esophagitis) as per consensus guidelines (including PPI non-response)\*
• Active eosinophilia on esophageal biopsy, with a peak count of least 15 EOS/hpf (eosinophils per high power field) from at least one esophageal level.
• Biopsies from the stomach and duodenum that have ruled out alternative etiologies in all children and in adults with abnormal endoscopic findings or when other gastric or small intestinal conditions are clinical possibilities. If these samples have been obtained during a previous endoscopic evaluation and in the judgement of the site-Investigator the patient has not had a clinically significant change that would merit repeat gastric/duodenal biopsies, then prior normal gastric and duodenal biopsies are acceptable to exclude alternate etiologies.
• Active symptoms of dysphagia with more than 3 episodes of dysphagia over a period of 2 weeks during the screening period, and an Eosinophilic Esophagitis Symptom Activity Index (EEsAI; see below for details) score of ≥ 27 at baseline.
• Able to read, comprehend, and sign consent form.
• Have maintained a stable diet for 6 weeks prior to enrollment.
• Able to maintain a stable diet throughout the duration of the study period.
• Female subjects of childbearing potential who have had their first menses agree to use a highly effective method of birth control during the study and for 30 days after the last dose of study drug. Female subjects with reproductive potential who are using systemic contraceptives (e.g., oral contraceptives, injectable contraceptives, implantable/insertable hormonal contraceptive products, or transdermal patches) to prevent pregnancy must have stable use for ≥28 days prior to screening.
• PPI non-response is defined as \>15 eos/hpf after at least 6 weeks of high dose administration (40mg total per day or higher) of any approved PPI medication or documented evidence of intolerance or allergy to PPIs. The length of the PPI trial period or documented intolerance/allergy will be determined according to the local clinical standard of care.

You may not qualify if:

• Esophageal dilation within 8 weeks of the screening endoscopy.
• Inability to pass a standard upper endoscope (8-10mm) due to esophageal narrowing or stricturing.
• Swallowed/topical steroids for EoE within 4 weeks of the screening endoscopy, or a course of systemic corticosteroids within 8 weeks of the screening endoscopy.
• Not having maintained a stable diet for at least 6 weeks preceding the screening endoscopy.
• Initiation, discontinuation, or change of dose regimen of PPIs; leukotriene inhibitors; or nasal, inhaled, and/or orally administered topical corticosteroids for any condition (such as gastroesophageal reflux disease, asthma, or allergic rhinitis) within the 8 weeks prior to the qualifying esophagogastroduodenoscopy (EGD).
• Presence of concomitant eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), eosinophilic colitis (EC), Crohn's disease, ulcerative colitis, or celiac disease.
• History of malignancy within 5 years prior to screening, except completely treated in situ carcinoma of the cervix and completely treated non-metastatic squamous or basal cell carcinoma of the skin.
• History of achalasia.
• Prior esophageal surgery.
• History of bleeding disorder or esophageal varices.
• Active parasitic infection or suspicion of an active parasitic infection, which, in the opinion of the site-Investigator, has not been previously evaluated or treated. Subjects presenting with signs of active parasitic infection or suspicion of active parasitic infection as assessed by current diarrhea and/or blood or mucus in stool will be referred to their clinical physician for further testing to rule out parasitic infection.
• Any other active infections judged at the discretion of the site-Investigator.
• Any other medical or psychological condition that, in the opinion of the site-investigator, may present an unreasonable risk to the study patient as a result of his/her participation in this clinical trial, may make patient's participation unreliable, or may interfere with study assessments. The specific justification for patients excluded under this criterion will be noted in study documents.
• Patient or his/her immediate family is a member of the investigational team.
• Pregnancy or breastfeeding.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• GlaxoSmithKline: collaborator
• University of Utah: collaborator
• Northwestern University: collaborator
• MNGI Digestive Health, P.A.: collaborator

Study Sites (4)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MNGI Digestive Health, P.A.

Minneapolis, Minnesota, 55446, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Dellon ES, Peterson KA, Mitlyng BL, Iuga A, Bookhout CE, Cortright LM, Walker KB, Gee TS, McGee SJ, Cameron BA, Galanko JA, Woosley JT, Eluri S, Moist SE, Hirano I. Mepolizumab for treatment of adolescents and adults with eosinophilic oesophagitis: a multicentre, randomised, double-blind, placebo-controlled clinical trial. Gut. 2023 Oct;72(10):1828-1837. doi: 10.1136/gutjnl-2023-330337. Epub 2023 Jul 9.

  PMID: 37423717 DERIVED

MeSH Terms

Conditions

Eosinophilic Esophagitis

Interventions

mepolizumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Lindsay Cortright, MA
• Organization: University of North Carolina at Chapel Hill

lindsay_cortright@med.unc.edu

919-445-4911

Study Officials

• Evan S Dellon, MD, MPH

  UNC Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: September 4, 2018
• Study Start: March 20, 2019
• Primary Completion: June 6, 2022
• Study Completion: December 9, 2022
• Last Updated: August 23, 2023
• Results First Posted: June 23, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)