Dupilumab vs Fluticasone for Esophagitis

(DeTECTS Trial)

Overseen By Michelle Landis, BS

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must not be taking: Dupilumab

Disqualifiers: Esophageal disease, IBD, liver disease, 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

Compensation: Varies

Number of Visits: 8

Duration: 16 weeks

72 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to \[primary purpose: e.g., learn if intervention or health behavior can treat, prevent, diagnose etc.\] in \[describe participant population/primary condition; could include any of the following: sex/gender, age groups, healthy volunteers\]. The main question\[s\] it aims to answer \[is/are\]: Does dupilumab or swallowed topical fluticasone improve the diameter of the esophagus more? Does dupilumab or swallowed topical fluticasone reduce inflammation in the esophagus more? Are comparative effective clinical trials feasible in this patient population? Researchers will compare dupilumab 300 mg weekly compared to swallowed fluticasone to see if there is a difference in treatment response. Participants will be asked to: * Be randomized to either dupilumab sq weekly or swallowed topical fluticasone twice daily. * Participate in 8 study visits over 52 weeks * Complete questionnaires * Have an endoscopy with biopsies and EndoFLIP measurements. * Swallow an Esophageal String Test

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but if you are on swallowed topical corticosteroids, you must be on a stable dose for 3 months before joining. Also, any diet restrictions and PPI use must remain unchanged for 8 weeks before and during the study.

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

Dupilumab has shown effectiveness in treating conditions with similar underlying inflammation, such as asthma, atopic dermatitis, and nasal polyps. Additionally, there is evidence suggesting improvement in eosinophilic esophagitis symptoms when Dupilumab is used for other allergic conditions. ^{1 2 3 4 5}

Is Dupilumab generally safe for humans?

Dupilumab has been shown to be generally safe for patients with moderate to severe asthma, with minimal adverse events compared to a placebo. However, it may cause increased blood eosinophils (a type of white blood cell) and has been associated with some ocular (eye-related) adverse reactions. ^{1 4 6 7 8}

How does the drug Dupilumab differ from other treatments for esophagitis?

Dupilumab is unique because it targets the IL-4 and IL-13 signaling pathways, which are involved in type 2 inflammation, and is already used for conditions like asthma and atopic dermatitis. This mechanism may help reduce inflammation in eosinophilic esophagitis, offering a novel approach compared to traditional treatments like fluticasone, which is a corticosteroid. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for individuals with Eosinophilic Esophagitis, a condition where the esophagus becomes inflamed with eosinophils. Participants will be involved in the study for about one year and must be willing to undergo random assignment to treatments, attend eight study visits, complete questionnaires, have an endoscopy with biopsies and EndoFLIP measurements, as well as swallow an Esophageal String Test.

Inclusion Criteria

I weigh at least 40 kg.

Seen at CHCO for clinical care

I have experienced swallowing difficulties at least twice a week in the last month.

Exclusion Criteria

Patients with a fasting morning cortisol <5 within 2 months of screening will not be enrolled. If repeat cortisol levels are normal, patients can be reconsented

Patients with a known gelatin allergy will be excluded from EST collection

I can be reconsidered for the trial if I meet all requirements after my stricture dilation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either dupilumab 300 mg weekly or swallowed topical fluticasone twice daily for 16 weeks

16 weeks

8 visits (in-person) over 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 weeks

Treatment Details

Interventions

• Dupilumab
• Fluticasone

Trial Overview The trial aims to determine whether dupilumab (300 mg weekly) or swallowed topical fluticasone (twice daily) is more effective at improving the diameter of the esophagus and reducing inflammation. It also assesses if such comparative clinical trials are feasible in this patient group.

Participant Groups

Group I: fluticasone (also known as Flovent) Active Control 1 Intervention

Group II: dupilumab (also known as Dupixent) Active Control 1 Intervention

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 Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Dupixent (dupilumab) is set to receive FDA approval for asthma treatment on October 20, expanding its use beyond atopic dermatitis.

Once approved, Dupixent will be part of a group of monoclonal antibodies, including Nucala, Cinqair, and Fasenra, that target type 2 inflammation in severe asthma, highlighting its role in managing this specific asthma phenotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupixent, a New Entrant In the Asthma Lists. Reinke, T.[2019]

Dupilumab is a monoclonal antibody that effectively targets the IL-4 receptor, significantly improving symptoms and quality of life in adults with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP) over 24 to 52 weeks in phase III studies.

The treatment was well tolerated and led to reductions in nasal polyp size, sinus opacification, and the need for systemic corticosteroids or nasal polyp surgery, showing benefits even in patients with comorbid asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab: A Review in Chronic Rhinosinusitis with Nasal Polyps. Hoy, SM.[2022]

In a real-life study of 12 patients with severe type-2 asthma, dupilumab treatment for 3 months led to significant improvements in asthma control (ACT score) and lung function (FEV1), indicating its efficacy in managing symptoms.

The treatment also resulted in a notable reduction in FeNO levels, a biomarker for type-2 inflammation, although blood eosinophil counts did not show significant change, suggesting that dupilumab effectively targets the IL4/IL13 pathway in asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early effectiveness of type-2 severe asthma treatment with dupilumab in a real-life setting; a FeNO-driven choice that leads to winning management. Carpagnano, GE., Scioscia, G., Buonamico, E., et al.[2022]

Dupilumab is a monoclonal antibody that targets the IL-4 receptor, blocking signals from IL-4 and IL-13, and is currently in phase III trials for treating moderate-to-severe asthma, showing promise for both eosinophilic and non-eosinophilic asthma phenotypes.

While dupilumab appears to be generally well tolerated, further large-scale studies are necessary to fully evaluate its long-term safety and efficacy, especially in pediatric populations where data is currently lacking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab for the treatment of asthma. Santini, G., Mores, N., Malerba, M., et al.[2019]

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 significantly improves lung function and asthma control in patients with moderate to severe asthma, as evidenced by better forced expiratory volume and asthma control questionnaire scores over 12 and 24 weeks in 13 trials.

The treatment is generally safe, showing no significant increase in adverse events compared to placebo, although it was associated with higher blood eosinophil levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab efficacy and safety in patients with moderate to severe asthma: A systematic review and meta-analysis. Zaazouee, MS., Alwarraqi, AG., Mohammed, YA., et al.[2022]

In the Phase 3 LIBERTY ASTHMA QUEST study, dupilumab significantly reduced severe asthma exacerbation rates by up to 67% compared to placebo in patients with elevated eosinophils, regardless of their inhaled corticosteroid dose or baseline lung function.

Dupilumab also improved lung function (measured by FEV1), asthma control, quality of life, and reduced levels of fractional exhaled nitric oxide (FeNO) across all patient subgroups, demonstrating its efficacy in managing moderate-to-severe asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab Efficacy in Patients Stratified by Baseline Treatment Intensity and Lung Function. Pavord, ID., Siddiqui, S., Papi, A., et al.[2022]

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]

References

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

Dupixent, a New Entrant In the Asthma Lists. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Dupilumab: A Review in Chronic Rhinosinusitis with Nasal Polyps. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Early effectiveness of type-2 severe asthma treatment with dupilumab in a real-life setting; a FeNO-driven choice that leads to winning management. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Dupilumab for the treatment of asthma. [2019]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Dupilumab efficacy and safety in patients with moderate to severe asthma: A systematic review and meta-analysis. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Dupilumab Efficacy in Patients Stratified by Baseline Treatment Intensity and Lung Function. [2022]

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

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