Dupilumab for Eosinophilic Esophagitis

(DESTRICT Trial)

Recruiting in Chapel Hill (>99 mi)

Overseen By Lindsay Cortright, MA

Age: Any Age

Sex: Any

Trial Phase: Phase 4

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 52 weeks

30 Participants Needed

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. ^{1 2 3 4 5}

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. ^{1 2 3 4 6}

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. ^{1 2 3 7 8}

Research Team

Evan Dellon, MD

Principal Investigator

University of North Carolina, Chapel Hill

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

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

Treatment Details

Interventions

• Dupilumab

Trial Overview 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.

Participant Groups

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

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

Regeneron Pharmaceuticals

Industry Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

In a study involving 240 patients with eosinophilic oesophagitis, dupilumab treatment maintained significant improvements in eosinophil counts and symptoms over 52 weeks, demonstrating its long-term efficacy.

Weekly administration of dupilumab was more effective than biweekly dosing, with 85% of patients on weekly dupilumab achieving a peak eosinophil count of 6 eos/hpf or less, highlighting the importance of dosing frequency in treatment outcomes.

NCBI (Pubmed)

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. Rothenberg, ME., Dellon, ES., Collins, MH., et al.[2023]

In a study of 46 patients with severe, treatment-refractory fibrostenotic eosinophilic esophagitis (EoE), dupilumab treatment led to significant improvements in endoscopic, histologic, and symptomatic outcomes after a median of 6 months.

The treatment resulted in an 80% histologic response rate, with a marked decrease in eosinophil counts and a significant increase in esophageal diameter, indicating effective management of this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Efficacy of Dupilumab in Severe, Treatment-Refractory, and Fibrostenotic Patients With Eosinophilic Esophagitis. Lee, CJ., Dellon, ES.[2023]

Dupilumab (Dupixent) is the first medication approved for the treatment of eosinophilic esophagitis, marking a significant advancement in managing this condition.

It is approved for use in both adults and children aged 12 years and older who weigh at least 40 kilograms, highlighting its safety and efficacy for a specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Indication for Dupilumab. Aschenbrenner, DS.[2022]

Dupilumab, a monoclonal antibody that inhibits interleukin-4 and interleukin-13 signaling, showed promising results in achieving clinical and histopathologic remission in three pediatric patients with non-eosinophilic esophagitis gastrointestinal disorders (EGID) who did not respond to standard treatments.

This study suggests that dupilumab may be a potential new treatment option for pediatric patients with eosinophilic gastrointestinal disorders, as it effectively reduced mucosal eosinophilia in multiple segments of the gastrointestinal tract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case Series on the Use of Dupilumab for Treatment of Refractory Eosinophilic Gastrointestinal Disorders. Patel, N., Goyal, A., Thaker, A., et al.[2023]

In a phase 2 trial involving 47 adults with eosinophilic esophagitis (EoE), dupilumab significantly reduced dysphagia symptoms and histological markers of the disease compared to placebo, indicating its efficacy in treating EoE.

Dupilumab also improved esophageal distensibility by 18% and was generally well tolerated, although some patients experienced injection-site reactions and nasopharyngitis more frequently than those receiving placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis. Hirano, I., Dellon, ES., Hamilton, JD., et al.[2021]

Dupilumab (Dupixent) has been associated with a risk of ocular adverse reactions, highlighting the importance of monitoring patients for eye-related side effects during treatment.

Prompt management of any ocular issues is essential for patients receiving dupilumab, ensuring their safety and well-being while benefiting from the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety update: dupilumab and ocular adverse reactions. [2022]

In a study of 45 patients with eosinophilic esophagitis (EoE) who were treated with dupilumab for other allergic conditions, 22 out of 26 showed a significant reduction in eosinophil counts in their esophagus after treatment, indicating effective histologic improvement.

The majority of patients (28 out of 45) reported symptom improvement, with 24 achieving complete resolution, and many were able to reduce their EoE medications or expand their diets, demonstrating dupilumab's efficacy in managing EoE symptoms when used for other atopic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in eosinophilic esophagitis when using dupilumab for other indications or compassionate use. Spergel, BL., Ruffner, MA., Godwin, BC., et al.[2022]

Dupilumab, a monoclonal antibody used to treat conditions like asthma and atopic dermatitis, can cause hypereosinophilia (high eosinophil levels) as a potential adverse effect, which poses a challenge for clinicians.

An algorithm has been proposed to help manage dupilumab-induced hypereosinophilia, allowing for proper investigation of related health issues while minimizing unnecessary discontinuation of the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management. Caminati, M., Olivieri, B., Dama, A., et al.[2022]

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]

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

Real-World Efficacy of Dupilumab in Severe, Treatment-Refractory, and Fibrostenotic Patients With Eosinophilic Esophagitis. [2023]

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

New Indication for Dupilumab. [2022]

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

A Case Series on the Use of Dupilumab for Treatment of Refractory Eosinophilic Gastrointestinal Disorders. [2023]

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

Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis. [2021]

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

Safety update: dupilumab and ocular adverse reactions. [2022]

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

Improvement in eosinophilic esophagitis when using dupilumab for other indications or compassionate use. [2022]

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

Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management. [2022]