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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates two treatments, dupilumab and swallowed fluticasone, to determine which more effectively improves the size and reduces inflammation of the esophagus in people with eosinophilic esophagitis (EoE). EoE causes difficulty swallowing due to inflammation. Participants will receive either dupilumab injections or oral fluticasone to compare their effects. This trial is suitable for individuals aged 12 to 25 who frequently experience difficulty swallowing and have been diagnosed with EoE through a biopsy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that dupilumab is safe. Research indicates it reduces disease markers in children with eosinophilic esophagitis (EoE) and is generally well-tolerated. Most side effects are mild to moderate, such as injection site reactions or mild breathing symptoms.

Studies on fluticasone also demonstrate its effectiveness and safety in treating EoE. It provides long-term relief for children, with most side effects being mild, like throat irritation or hoarseness.

Both treatments have been well-studied and are safe for most people. However, discussing personal health concerns with a doctor before joining a trial is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for esophagitis, like proton pump inhibitors and topical steroids, Dupilumab (also known as Dupixent) targets the inflammatory pathway. It specifically blocks the IL-4 and IL-13 signaling, which are key drivers of inflammation in many allergic conditions. Researchers are excited about Dupilumab because it offers a novel approach by addressing the root cause of inflammation rather than just treating symptoms. On the other hand, Fluticasone (also known as Flovent) is a steroid that works by reducing inflammation locally in the esophagus, offering a more targeted approach compared to systemic treatments. These options have the potential to provide relief for patients who don't fully respond to existing therapies.

What evidence suggests that this trial's treatments could be effective for esophagitis?

This trial will compare the effectiveness of dupilumab and fluticasone in treating eosinophilic esophagitis (EoE). Research has shown that dupilumab, which participants may receive, effectively treats EoE by leading to histologic remission and significantly reducing the buildup of certain white blood cells in the esophagus. One study found that dupilumab reduced the peak number of these cells by over 100%, demonstrating its ability to significantly decrease swelling.

Fluticasone, another treatment option in this trial, is also effective for long-term EoE treatment. It is often used to maintain improvement and can help achieve histologic remission. Both treatments show promise in reducing swelling, but the specific benefits may vary for each person. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Group II: fluticasone (also known as Flovent) 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+

Published Research Related to This Trial

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 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 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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04394351

NCT04394351 | Study to Investigate the Efficacy and ... The Primary objective is to demonstrate the efficacy of dupilumab treatment compared with placebo in pediatric patients with active eosinophilic esophagitis ...

2. 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.

3. va.gov va.gov/formularyadvisor/DOC_PDF/MON_Dupilumab_DUPIXENT_in_Eosinophilic_Esophagitis_Monograph_Nov_2022.pdf

Dupilumab (DUPIXENT) in Eosinophilic Esophagitis ... Efficacy data for the approved dose of dupilumab in EoE (300 mg QW) are summarized in Table 2. Page 3. Dupilumab in EoE Monograph. 3. Table 2 Efficacy results ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2022/761055Orig1s040.pdf

761055Orig1s040 | FDA For the treatment of adult and pediatric patients ages 12 years and older, weighing at least 40 kg, with eosinophilic esophagitis. Page 2 ...

5. gastrojournal.org gastrojournal.org/article/S0016-5085(19)41415-7/fulltext

Efficacy of Dupilumab in a Phase 2 Randomized Trial ... At week 12, dupilumab reduced the peak esophageal intraepithelial eosinophil count by a mean 86.8 eosinophils per high-power field (reduction of 107.1%; P < .

6. 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, ...

7. 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 Press Release: Dupixent® (dupilumab) Phase 3 trial shows positive results in children. 1 to 11 years of age with eosinophilic esophagitis. 2022.

8. 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 ...

9. news.sanofi.us news.sanofi.us/2023-10-22-Dupixent-R-dupilumab-Phase-3-Results-show-sustained-efficacy-for-up-to-one-year-in-children-1-to-11-years-of-age-with-eosinophilic-esophagitis-EoE

Dupixent® (dupilumab) Phase 3 Results show sustained ... Data from this Phase 3 trial support the potential of dupilumab to treat EoE in children, with sustained efficacy and safety, which is ...