Dupilumab for Eosinophilic Esophagitis

(DESTRICT Trial)

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how well the drug dupilumab treats individuals with severe strictures and active Eosinophilic Esophagitis (EoE), a condition where the esophagus becomes inflamed due to an excess of eosinophils, a type of white blood cell. Participants in this open-label study will receive weekly injections of dupilumab for one year. Ideal candidates are those with active EoE who have not responded to standard treatments like proton pump inhibitors or topical steroids and have a history of a narrow esophagus or multiple esophageal dilations. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

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 is the safety track record for dupilumab?

Research has shown that dupilumab is generally safe and well-tolerated. In one study, all participants who received weekly dupilumab showed significant improvement in their condition over 52 weeks, with no major safety issues. Another study found that dupilumab helped more children with eosinophilic esophagitis achieve remission compared to those who took a placebo. Since the FDA has already approved dupilumab for other conditions, its safety has been well-studied. Most side effects are mild, such as reactions at the injection site or cold-like symptoms. Therefore, dupilumab is considered safe for treating eosinophilic esophagitis. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Dupilumab is unique because it targets interleukin-4 and interleukin-13, which are key drivers of inflammation in eosinophilic esophagitis (EoE). Unlike standard treatments like dietary management or topical steroids, which can be challenging to maintain or have side effects, dupilumab offers a targeted biological approach. Researchers are excited about its potential to reduce inflammation more effectively and improve symptoms for patients who may not respond adequately to existing therapies. Plus, the convenience of a weekly subcutaneous injection could make it a more attractive option for long-term management of EoE.

What is the effectiveness track record for dupilumab in treating Eosinophilic Esophagitis?

Research has shown that dupilumab, the treatment under study in this trial, effectively treats eosinophilic esophagitis (EoE), a condition causing inflammation in the esophagus. Studies indicate that it provides significant symptom relief, with patients experiencing up to a 76% reduction in symptoms over a year. Dupilumab also improved the esophagus by reducing eosinophils, the white blood cells involved in inflammation. In one study, all patients taking weekly dupilumab experienced a significant decrease in these cells. Overall, dupilumab has demonstrated strong results in managing EoE symptoms and reducing inflammation. ^{5 6 7 8 9}

Who Is on the Research Team?

Evan Dellon, MD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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, 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39998943/

Real-world Effectiveness of Dupilumab in Eosinophilic ... The pooled outcome for symptom improvement with dupilumab was 89.2% [95% Cl: 68.0%-97.0%; I2 =58%]. Peak eosinophil count improved markedly ...

2. dupixenthcp.com dupixenthcp.com/eoe/efficacy-safety/efficacy

Efficacy in EoE | DUPIXENT® (dupilumab) Week 52b: -23.4-point reduction (76%) from baseline after 52 weeks of treatment with DUPIXENT (n=29) · Week 52b: -21.7-point reduction (66%) from baseline after

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2205982

Dupilumab in Adults and Adolescents with Eosinophilic ... Among patients with eosinophilic esophagitis, subcutaneous dupilumab administered weekly improved histologic outcomes and alleviated symptoms of the disease.

4. gi.org gi.org/journals-publications/ebgi/eluri_dec2024/

Long Term Efficacy and Safety of Dupilumab for ... All 65 (100%) patients on weekly dupilumab achieved peak ≤15 eos/hpf after 52 weeks of treatment. Weekly dupilumab significantly reduced ...

5. sanofi.com sanofi.com/en/media-room/press-releases/2023/2023-10-22-19-00-00-2764338

Press Release: Dupixent® (dupilumab) Phase 3 Results ... Positive results from a Phase 3 trial demonstrated the efficacy and safety profile of Dupixent (dupilumab) for up to one year (52 weeks) in children aged 1 to ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT06693531?term=NCT06693531&rank=1

A U.S. Registry of Eosinophilic Esophagitis Adolescent and ... This observational research study is to better understand patients with eosinophilic esophagitis (EoE) who have recently been prescribed ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02379052

NCT02379052 | Study of Dupilumab in Adult Participants ... The primary objective of the study is to assess the clinical efficacy of repeat subcutaneous (SC) doses of dupilumab, compared with placebo, ...

8. io.nihr.ac.uk io.nihr.ac.uk/wp-content/uploads/2023/07/29964-Dupilumab-for-Eosinophilic-Oesophagitis-V1.0-MAY2023-NON-CONF.pdf

Health Technology Briefing May 2023 A Study to Determine the Safety and Tolerability of Dupilumab. (REGN668/SAR231893) in Patients Aged ≥6 to <18 Years With Atopic Dermatitis ( ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38924731/

Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 ... Dupilumab resulted in histologic remission in a significantly higher percentage of children with eosinophilic esophagitis than placebo.