Does your child have eosinophilic esophagitis (EoE)?

Study ID: STU-2019-0556

Summary

This study consists of three parts: Part a and Part B are 24-week treatment, randomized, double-blind, placebo-controlled study phases and Part C is a 28-week, open-label phase that will enroll patients from Part a and Part B. The primary objectives by study part are: Part a To determine the treatment effect of dupilumab compared with placebo in adult and adolescent patients with eoe after 24 weeks of treatment as assessed by histological and clinical measures and to inform/confirm the final sample size determination for Part B. note: Patients enrolled in Part a may not participate in Part B. Part B To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and adolescent patients with eoe after 24 weeks of treatment as assessed by histological and clinical measures. Part C To assess the safety and efficacy of dupilumab treatment in adult and adolescent patients with eoe after up to 52 weeks of treatment as assessed by histological [See protocol for complete text]

Participant Eligibility

Who can participate? (Additional criteria to be met prior to participation)

Adolescents between ages 12-18 years old
Adolescents that have been diagnosed with eosinophilic esophagitis by biopsy or a doctor
Adolescents who are willing to undergo an endoscopy procedure and allow the doctor to obtain biopsy samples from the esophagus, stomach and small intestine, as indicated.
Adolescents who are willing to receive an investigational subcutaneous (SQ) injection for eosinophilic esophagitis and are willing to participate for about 18 months (about 20 visits)

Who cannot participate? (Additional exclusion criteria to be reviewed prior to participation)

Those who are pregnant or breastfeeding
Those who have certain gastrointestinal disorders
Those who have a history of bleeding disorders
Those who are hepatitis B and HIV positive

What will you be asked to do? Participants will be asked to have a parent/guardian give investigational subcutaneous injections of dupilumab or placebo for EoE. There is a 2/3 chance of receiving dupilumab vs placebo for the first half of the study. For the second half of the study ALL participants will recieve dupilumab. Participants will be asked to undergo 3 endoscopy procedures which include obtaining biopsies of esophagus, stomach and small intestine, as indicated. Other assessments include vital signs, blood draws, EKG and physical examinations.

For additional information about the study, visit clinicaltrials.gov.

I am Interested

Cancer Related: No
Healthy Volunteers: No
UT Southwestern Principal Investigator: CHRISTOPHER PAUL PARRISH

Contact:

Amy Arneson

amy.arneson@childrens.com

eosinophilic esophagitis (eoe) is a chronic, inflammatory, allergic/immune-mediated disease of the esophagus. The disease is characterized by local eosinophilic inflammation leading to symptoms of esophageal dysfunction. although considered a rare disease, the current prevalence is estimated at 22.7 per 100,000 worldwide (arias, 2016) and appears to be on the increase. eosinophilic esophagitis has been reported in all ages; however, most cases are in children and adults younger than 50 years. The primary clinical manifestations of eoe in both adults and children over 10 years of age are dysphagia and food impaction. These symptoms lead to substantially impaired quality of life (QoL). The inflammatory damage to the esophageal epithelium results in symptoms of esophageal dysfunction, such as dysphagia. Chronic inflammation of the esophagus may also lead to remodeling, stricture formation, and fibrosis. The fibrotic aspect of progressed disease is not well understood, and whether or not this can be reversed with treatment is unknown. Dupilumab is a human monoclonal immunoglobulin G4 (igG4) antibody (ab) that inhibits iL-4 and iL-13 signaling by specifically binding to the iL-4 receptor alpha (iL-4R[RegisteredTM]) subunit shared by the iL-4 and iL-13 receptor complexes. Blocking iL-4R[RegisteredTM] with dupilumab inhibits iL-4 and iL-13 Type 2 cytokine-induced responses, including the release of pro-inflammatory cytokines, chemokines, and ige. additionally, preclinical data demonstrate that treatment with dupilumab prevents infiltration of eosinophils into tissues. The primary objectives of the study by study part are: Part a-To determine the treatment effect of dupilumab compared with placebo in adult and adolescent patients with eoe after 24 weeks of treatment as assessed by histological and clinical measures, and to inform/confirm the final sample size determination for Part B. Part B- To demonstrate the efficacy of dupilumab treatment compared with placebo in adult and adolescent patients with eoe after 24 weeks of treatment as assessed by histological and clinical measures. Part C- To assess the safety and efficacy of dupilumab treatment in adult and adolescent patients with eoe after up to 52 weeks of treatment as assessed by histological and clinical measures. The secondary objectives of the study are: 1: To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 52 weeks in adult and adolescent patients with eoe. 2.- To explore the relationship between dupilumab concentration and responses in adult and adolescent patients with eoe, using descriptive analyses. Hypothesis- in adult and adolescent patients [GreaterThanorequalTo]12 years of age with eoe, treatment with dupilumab will result in a statistically significant benefit compared to treatment with placebo, as measured by: 1.Relief of dysphagia, assessed by change in the Dysphagia Symptom Questionnaire (DSQ) score. 2.Reduction in eosinophilic esophageal infiltration, assessed by change in esophageal intraepithelial eosinophil count. 3. improvement in endoscopically identified esophageal mucosal inflammatory and remodeling features, assessed by change in the eosinophilic esophagitis-endoscopic Reference Score (eoe-eReFS)