Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 16 of 20 for:    Recruiting Studies | Interventional Studies | Eosinophilic Esophagitis

Mepo for EoE Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03656380
Recruitment Status : Recruiting
First Posted : September 4, 2018
Last Update Posted : January 28, 2021
Sponsor:
Collaborators:
GlaxoSmithKline
University of Utah
Northwestern University
MNGI Digestive Health, P.A.
Information provided by (Responsible Party):
University of North Carolina, Chapel Hill

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 after an initial 3 month treatment course, and will also assess the impact of an additional 3 months of treatment.

Condition or disease Intervention/treatment Phase
EoE Eosinophilic Esophagitis Drug: Mepolizumab 300 mg Drug: Mepolizumab 100 mg Other: Placebo Phase 2

Detailed Description:

This is a multi-center, randomized, double blind, parallel-arm, placebo controlled trial of mepolizumab. After the first 3 month blinded phase, there will be a second 3 month blinded phase where all patients receive active medication, but the dose will be lower in the subjects initially randomized to the placebo arm.

In the first arm, subjects will receive mepolizumab 300 mg SQ monthly for 3 months. In the second arm, subjects will receive a placebo SQ injection monthly for 3 months. Both groups will have the injection administered under direct observation in a Clinical & Translational Research Center (CTRC) or other clinic to ensure proper administration and compliance. Each visit will also provide an opportunity for symptom questionnaires to be completed and for blood samples to be drawn. After 3 months (the time point where the primary outcome is assessed), all subjects initially randomized to active treatment will continue with mepolizumab dosing 300 mg SQ monthly, and will remain blinded. All subjects initially randomized to placebo will receive mepolizumab 100mg SQ monthly, and will remain blinded. Of note, no dietary changes, changes in baseline Proton Pump Inhibitor (PPI) medication dose, changes in inhaled or intranasal steroid doses, or administration or oral, topical/swallowed, or systemic steroids will be allowed during the study period. Subjects will undergo endoscopy after the first blinded phase (at 3 months) and after the second blinded phase (after 6 months).

Layout table for study information
Study Type : Interventional
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Double Blind, Parallel-arm, Placebo Controlled Trial of Mepolizumab for Treatment of Adults and Adolescents With Active Eosinophilic Esophagitis and Dysphagia-predominant Symptoms
Actual Study Start Date : March 20, 2019
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022


Arm Intervention/treatment
Experimental: Mepolizumab 300 mg
Subjects will receive Mepolizumab 300 mg subcutaneously (SQ) monthly for 6 months
Drug: Mepolizumab 300 mg
Mepolizumab 300 mg subcutaneous injection
Other Name: Nucala

Placebo, followed by Mepolizumab 100 mg
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
Mepolizumab 100 mg subcutaneous injection
Other Name: Nucala

Other: Placebo
Saline subcutaneous injection
Other Name: Saline




Primary Outcome Measures :
  1. Mean Change in Dysphagia from Baseline to 3 months Post-treatment [ Time Frame: Baseline, Month 3 Post-Treatment ]
    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.


Secondary Outcome Measures :
  1. Proportion of Participants with a Clinical Remission (EEsAI Score of ≤ 20 points) after 3 months of treatment [ Time Frame: After 3 months of treatment ]
    The EEsAI 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.

  2. Proportion of Participants with a Clinical Response (EEsAI Score Decrease of ≥ 20 points) after 3 months of treatment [ Time Frame: After 3 months of treatment ]
    The EEsAI 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.

  3. Absolute Peak Eosinophil count (measured in eos/hpf) after 3 months of treatment [ Time Frame: After 3 months of treatment ]
    Absolute peak eosinophil count (measured in EOS/hpf) after 3 months of treatment.

  4. Histologic Response Levels after 3 Treatment Months [ Time Frame: After 3 months of treatment ]
    Histologic levels for <15, ≤ 6, and ≤ 1 EOS/hpf.

  5. Mean Change in EoE Endoscopic Reference Score (EREFS) from Baseline to 3 months Post-treatment [ Time Frame: Baseline, 3 months post-treatment ]
    Mean change in severity of endoscopic findings as measured by the EoE Endoscopic Reference Score (EREFS). The EREFS, measures features of EoE including esophageal edema, rings, exudate, furrows, and strictures. The instrument grades edema and furrows as absent (0) or present (1); rings as absent (0), mild (1, subtle circumferential ridges), moderate (2, distinct rings) and severe (3, rings that impair passage of a standard adult diagnostic endoscope); exudates as absent (0), mild (1, less than 10% of the esophageal surface area) or severe (2, greater or equal to 10% of the esophageal surface area); and strictures as absent (0) or present (1) with an estimation of the minimal luminal diameter. Higher scores indicate more severe disease (range 0 - 9).

  6. Mean change in the Straumann Dysphagia Instrument (SDI) Score from Baseline to 3 months Post-treatment [ Time Frame: Baseline, 3 months post-treatment ]
    The Straumann Dysphagia Instrument (SDI) is a direct measure of dysphagia frequency and severity which is completed by participants and reported over the previous week. The score ranges from 0-9, with higher scores indicating more severe dysphagia.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   16 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 16-75
  • Diagnosis of EoE as per consensus guidelines (including PPI non-response). PPI non-response is defined as >15 EOS/hpf after 8 weeks of high dose administration (40mg total per day or higher) of any approved PPI medication.
  • Active eosinophilia on esophageal biopsy, with a peak count of least 15 EOS/hpf 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. See section 5.3 for additional details.

Exclusion Criteria:

  • 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 systemic corticosteroids within 8 weeks of the screening endoscopy.
  • Not having maintained a stable diet for at least 6 weeks preceding enrollment.
  • 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.
  • Women of children bearing potential who are not on highly-effective contraception.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03656380


Contacts
Layout table for location contacts
Contact: Susan E Moist, MPH 919-966-7655 susan_moist@med.unc.edu
Contact: Lindsay M Cortright, MA 919-445-0203 lindsay_cortright@med.unc.edu

Locations
Layout table for location information
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Ikuo Hirano, MD    312-695-4036    i-hirano@northwestern.edu   
Contact: Meagan Yong    312-503-2737    meagan.yong@northwestern.edu   
Principal Investigator: Ikuo Hirano, MD         
United States, Minnesota
MNGI Digestive Health, P.A. Recruiting
Minneapolis, Minnesota, United States, 55446
Contact: Irena Davies    612-870-5587    irena.davies@mngi.com   
Principal Investigator: Benjamin Mitlyng, MD         
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Lindsay M Cortright, MA    919-445-0203    lindsay_cortright@med.unc.edu   
Principal Investigator: Evan S Dellon, MD, MPH         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Kathryn Peterson, MD       Kathryn.Peterson@hsc.utah.edu   
Contact: Stephanie McDonough    801-585-0894    Stephanie.Mcdonough@hsc.utah.edu   
Principal Investigator: Kathryn Peterson, MD         
Sponsors and Collaborators
University of North Carolina, Chapel Hill
GlaxoSmithKline
University of Utah
Northwestern University
MNGI Digestive Health, P.A.
Investigators
Layout table for investigator information
Principal Investigator: Evan S Dellon, MD, MPH UNC Chapel Hill
Layout table for additonal information
Responsible Party: University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT03656380    
Other Study ID Numbers: 18-0431
First Posted: September 4, 2018    Key Record Dates
Last Update Posted: January 28, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases