Dupilumab for Eosinophilic Esophagitis

(DESTRICT Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Evan Dellon, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Biologics, Blood thinners

Disqualifiers: Other eosinophilic GI disease, Recent steroid use, Recent live vaccine, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to determine how well an FDA-approved drug, dupilumab, works to treat patients with severe strictures and active Eosinophilic Esophagitis (EoE). This is an open-label study, meaning everyone in the study will receive dupilumab. Participants will have a screening visit where they will complete surveys and undergo an endoscopy (EGD). Blood and biopsies (small tissue samples) will also be collected. If eligible and enrolled into the study, participants will receive weekly subcutaneous (under the skin) injections of dupilumab for 52 weeks (one year). The first dose of dupilumab will be administered at the week 1 visit by a clinician and participants will receive training on how to self-administer the remaining doses. Participants will return for study visits every at weeks 4, 8, 12, 18, 24, 30, 36, 44, and 52. During these visits, vital signs (temperature, heart rate, etc.) will be collected and participants will complete surveys. During visits at week 12, 24, and 52, blood will be collected and an endoscopy with biopsy will be performed. At 64 weeks (12 weeks after the last dose of dupilumab), participants assigned male at birth (AMAB) will be contacted about their / their partner's pregnancy status and participants assigned female at birth (AFAB) may be asked to come for an in-person visit to complete a urine pregnancy test.

Will I have to stop taking my current medications?

The trial requires that you do not change your dose of proton pump inhibitors (PPI) and avoid using topical or systemic steroids for EoE during the study. If you are on blood thinners, you may need to stop them briefly before certain procedures.

What data supports the effectiveness of the drug Dupilumab for treating eosinophilic esophagitis?

Research shows that Dupilumab is effective in treating eosinophilic esophagitis by reducing inflammation in the esophagus. It has been approved for use in adults and children over 12 years old, and studies have shown it helps patients who have not responded to other treatments.

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Is Dupilumab safe for humans?

Dupilumab has been studied for its safety in treating eosinophilic esophagitis and other conditions. While it is generally considered safe, there is a known risk of eye-related side effects, which require prompt management.

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How is the drug Dupilumab unique in treating eosinophilic esophagitis?

Dupilumab is unique because it is the first drug approved specifically to treat eosinophilic esophagitis, targeting the underlying inflammation by blocking the receptor for interleukin (IL)-4 and IL-13, which are involved in the disease's immune response.

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Eligibility Criteria

This trial is for individuals with severe narrowing of the esophagus (strictures) due to Eosinophilic Esophagitis (EoE), a chronic allergic/immune condition. Participants must have active symptoms and will be screened with an endoscopy. The study requires weekly self-administered injections for one year, regular check-ups, blood tests, and additional endoscopies.

Inclusion Criteria

Diagnosis of EoE per 2018 AGREE consensus guidelines

I am 16 years old or older.

I did not respond well to PPI and steroid treatments for over 8 weeks.

Exclusion Criteria

Inability to read or understand English

Prior allergic reaction to dupilumab or its components, or dupilumab intolerance

Study doctor's determination that it would not be medically safe to complete an EGD

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive weekly subcutaneous injections of dupilumab for 52 weeks

52 weeks

10 visits (in-person) at weeks 1, 4, 8, 12, 18, 24, 30, 36, 44, and 52

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pregnancy status check

12 weeks

1 visit (in-person) for AFAB participants, phone call for AMAB participants

Participant Groups

The trial is testing Dupilumab, an FDA-approved drug, to see how effective it is in treating severe strictures caused by EoE. All participants will receive the drug through under-the-skin injections once a week for 52 weeks and their health progress will be monitored regularly.

Group I: Open Label dupilumab Experimental Treatment 1 Intervention

Open label dupilumab 300mg injection given subcutaneously weekly, for 52 weeks.

Dupilumab is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Dupixent for:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis

🇪🇺 Approved in European Union as Dupixent for:

• Atopic dermatitis
• Asthma
• Chronic rhinosinusitis with nasal polyps
• Eosinophilic esophagitis

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of North Carolina at Chapel Hill Chapel Hill, NC

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill Lead Sponsor

Regeneron Pharmaceuticals Industry Sponsor

Sanofi Industry Sponsor

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dupilumab up to 52 weeks in adults and adolescents with eosinophilic oesophagitis (LIBERTY EoE TREET study): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. [2023] Long-term management options that specifically target the underlying inflammation in eosinophilic oesophagitis are needed. Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13; we aimed to assess its long-term efficacy and safety in adults and adolescents with eosinophilic oesophagitis enrolled in part B of the LIBERTY EoE TREET study who continued to part C (part B-C).

2. United States pubmed.ncbi.nlm.nih.gov

Real-World Efficacy of Dupilumab in Severe, Treatment-Refractory, and Fibrostenotic Patients With Eosinophilic Esophagitis. [2023] Dupilumab is approved for treatment of eosinophilic esophagitis (EoE), but real-world data are lacking. We aimed to determine the real-world efficacy of dupilumab in patients with severe, treatment-refractory, and fibrostenotic EoE.

3. United States pubmed.ncbi.nlm.nih.gov

New Indication for Dupilumab. [2022] Dupilumab (Dupixent) has been approved to treat eosinophilic esophagitis in adults and children ages 12 years and older who weigh at least 40 kilograms. This is the first drug approved to treat this disease.

4. United States pubmed.ncbi.nlm.nih.gov

A Case Series on the Use of Dupilumab for Treatment of Refractory Eosinophilic Gastrointestinal Disorders. [2023] The incidence and prevalence of eosinophilic esophagitis (EoE), eosinophilic gastritis (EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC) are increasing ( 1 ). These conditions will inevitably become more widely recognized and better understood. There is currently no Food and Drug Administration (FDA)-approved treatment for EoE, but there are standard-of-care treatments that are well established and widely used. In contrast, there is a paucity of data regarding standard-of-care treatment for non-EoE eosinophilic gastrointestinal disorders (EGID). We identified 3 patients that all achieved clinical and histopathologic remission on dupilumab, a monoclonal antibody that blocks the downstream signaling of interleukin (IL)-4 and IL-13. These patients had extra-esophageal forms of EGID with two patients failing to achieve remission on standard-of-care therapies and one patient experiencing significant side effects on swallowed budesonide therapy. The reduction in mucosal eosinophilia in several GI tract segments in these 3 patients highlights a new potential clinical indication for dupilumab in the treatment of pediatric EGID patients.

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis. [2021] Eosinophilic esophagitis (EoE) is an allergen-mediated inflammatory disease with no approved treatment in the United States. Dupilumab, a VelocImmune-derived human monoclonal antibody against the interleukin (IL) 4 receptor, inhibits IL4 and IL13 signaling. Dupilumab is effective in the treatment of allergic, atopic, and type 2 diseases, so we assessed its efficacy and safety in patients with EoE.

6. England pubmed.ncbi.nlm.nih.gov

Safety update: dupilumab and ocular adverse reactions. [2022] Overview of: Medicines and Healthcare products Regulatory Agency. Dupilumab (Dupixent▼): risk of ocular adverse reactions and need for prompt management. Drug Safety Update 2022;16(4): 1.

7. United States pubmed.ncbi.nlm.nih.gov

Improvement in eosinophilic esophagitis when using dupilumab for other indications or compassionate use. [2022] Dupilumab has been approved to treat atopic dermatitis, asthma, and nasal polyps and is in active clinical trials for the treatment of eosinophilic esophagitis (EoE). Given its shared immunopathology, we hypothesized that EoE symptoms and inflammation would improve when dupilumab therapy was used for other allergic indications.

8. England pubmed.ncbi.nlm.nih.gov

Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management. [2022] Dupilumab is a human monoclonal antibody that targets both IL-4 and IL-13 signaling. It is currently indicated for the treatment of asthma, moderate-to-severe atopic dermatitis, and chronic rhinosinusitis with nasal polyps (CRSwNP). Eosinophilia has been reported as a potential adverse event in treated patients.