Dupilumab for Eosinophilic Esophagitis

Overseen By Ravinder Mittal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, San Diego

Must be taking: Dupilumab

Must not be taking: Systemic corticosteroids, Omalizumab, Methotrexate, others

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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: 2

Duration: 12 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to research Dupilumab, an FDA approved medication in treating patients diagnosed with Eosinophilic esophagitis (EoE). The drug works by controlling allergic inflammation of the esophagus. The esophagus is a food pipe that transfers food from the mouth into the stomach. Participants with EoE have dysfunction of the muscle of the esophagus (impaired peristalsis) that is not favorable for the transport function. Main question this study aims to answer is: Whether Dupilumab helps improve muscle activity of the esophagus in participants with EOE? Participants will: Take Dupilumab every week for 12 weeks. Visit the clinic before and after starting the medication. Keep a diary of symptoms.

Will I have to stop taking my current medications?

The trial requires that you have not taken inhalational, oral, or IV steroids for at least 8 weeks before starting. If you're on a stable dose of certain medications like proton pump inhibitors, leukotriene inhibitors, or corticosteroids, you can continue them but must not change the dose during the study. Always discuss with the investigators before making any changes to your medications.

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 5 6}

What makes the drug Dupilumab unique for 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 5 7 8}

Eligibility Criteria

This trial is for patients with Eosinophilic Esophagitis (EoE), a condition where the esophagus becomes inflamed due to allergies. Participants should have muscle dysfunction in their esophagus, affecting food movement. The study excludes details on specific inclusion and exclusion criteria.

Inclusion Criteria

I can take medication under the skin and will follow a 12-week treatment plan.

Provision of signed and dated informed consent form

Stated willingness to comply with all study procedures and availability for the duration of the study including regular follow-up with the study monitor

Exclusion Criteria

Abnormal lab values at screening

I haven't had cancer in the last 5 years, except for treated skin or cervical cancer.

I am currently being treated for liver disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive Dupilumab once a week for 12 weeks to assess its effect on esophageal peristaltic function

12 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Dupilumab

Trial Overview The study tests Dupilumab, an FDA-approved drug for allergic inflammation, to see if it improves the muscle function of the esophagus in EoE patients. Participants will take Dupilumab weekly for 12 weeks and monitor symptoms in a diary.

Participant Groups

Group I: EoE participants treated with Dupilumab Experimental Treatment 1 Intervention

All the participants will be treated with once a week subcutaneous injection of Dupilumab 300 mg through for 12 weeks. There is no placebo arm in the study.

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 California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

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

Findings from Research

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]

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]

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]

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]

References

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

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

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

New Indication for Dupilumab. [2022]

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

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

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

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

5. 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]

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

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

7. England pubmed.ncbi.nlm.nih.gov

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

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

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