Dupilumab for Esophagitis

Recruiting at 49 trial locations

Overseen By Trial Transparency email recommended (Toll free for US & Canada)

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Sanofi

Must not be taking: Topical corticosteroids, Dupilumab

Disqualifiers: Hypereosinophilic syndrome, Crohn's, others

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: 21

64 Participants Needed

Trial Summary

What is the purpose of this trial?

This is parallel, Phase 4 study which consists of a 24 week (0.5 years) randomized, double blind, placebo controlled, 2-arm treatment period followed by an open label segment of 104 weeks (2 years) for a total of 128 weeks (2.5 years) to evaluate the effect of dupilumab treatment on esophageal function, and remodeling in adults with eosinophilic esophagitis. Duration of study period (per participant) * Screening period: Up to 12 weeks before Week 0 * Randomized double-blind period: 24 weeks * Open label period: 104 weeks * Post Investigational Medicinal Product (IMP) intervention follow-up period: up to 12 weeks or until the participants switch to commercialized dupilumab, whatever comes first. There will be ten (10) site visits, and five (5) direct-to-participant IMP delivery visits (except if prohibited by local regulatory authorities or if participant is not willing. In this case, IMP will be dispensed at the study site).

Will I have to stop taking my current medications?

The trial requires that you stop taking swallowed topical corticosteroids at least 8 weeks before starting. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is dupilumab generally safe for humans?

Dupilumab has a favorable safety profile with few, reversible side effects in various conditions, including atopic dermatitis and asthma. It is generally considered safe, although it may cause some eye-related side effects and increased blood eosinophils (a type of white blood cell) in some cases. ^{1 2 3 4 5}

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, a condition with no prior approved treatments. It works by blocking certain proteins (IL-4 and IL-13) involved in inflammation, which is different from other treatments that may not target these specific pathways. ^{4 6 7 8 9}

Research Team

Clinical Sciences & Operations

Principal Investigator

Sanofi

Eligibility Criteria

Adults with a confirmed diagnosis of Eosinophilic Esophagitis (EoE) who experience at least two episodes of difficulty swallowing solid food per week and weigh over 40 kg can join. Those without proper biopsy confirmation or outside the weight criteria cannot participate.

Inclusion Criteria

A documented diagnosis of EoE by endoscopic biopsy

Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration

I weigh at least 40 kg.

Exclusion Criteria

Active Helicobacter pylori infection

Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to10 mm upper endoscope or any critical esophageal stricture that requires dilation at screening

Initiation or change of a food elimination diet regimen or reintroduction of a previously eliminated food group in the 6 weeks prior to screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 12 weeks

1 visit (in-person)

Randomized double-blind treatment

Participants receive either dupilumab or placebo in a double-blind manner

24 weeks

10 site visits, 5 direct-to-participant IMP delivery visits

Open-label treatment

Participants receive open-label dupilumab treatment

104 weeks

10 site visits, 5 direct-to-participant IMP delivery visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 weeks

Treatment Details

Interventions

• Dupilumab

Trial Overview The study is testing Dupilumab against a placebo to see its effects on esophageal function in EoE patients. Initially, participants are randomly assigned to receive either Dupilumab or placebo for six months, followed by everyone receiving Dupilumab for an additional two years.

Participant Groups

Group I: Dupilumab Experimental Treatment 1 Intervention

Subcutaneous injection (SC) as per protocol

Group II: Placebo Placebo Group 1 Intervention

SC injection as per protocol

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?

Sanofi

Lead 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

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

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 is an effective treatment for type 2 inflammatory diseases like atopic dermatitis, asthma, and nasosinusal polyposis, as it inhibits the IL-4 receptor, blocking the action of key cytokines involved in these conditions.

The drug has a favorable safety profile, with few and reversible side effects, making it a promising option for patients who do not respond well to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dupilumab: beyond atopic dermatitis, off-label use in dermatology]. Russo, G., Laffitte, E.[2023]

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 is a monoclonal antibody that targets the IL-4 receptor, effectively inhibiting the action of IL-4 and IL-13, which are key players in allergic diseases.

It received its first approval in March 2017 for treating moderate-to-severe atopic dermatitis in adults who do not respond well to topical treatments, and is also being developed for asthma, nasal polyps, and eosinophilic esophagitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab: First Global Approval. Shirley, M.[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]

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 (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]

In a study of 818 adults with moderate-to-severe atopic dermatitis treated with dupilumab for at least 16 weeks, 12% of patients successfully spaced their doses or withdrew treatment while still maintaining effectiveness.

Key predictors for successful dose spacing or treatment withdrawal included having non-cutaneous atopic manifestations, a prurigo nodularis phenotype, and being older at the start of treatment, suggesting specific patient profiles can benefit from adjusted treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of clinical predictors for dupilumab dose spacing in adults with atopic dermatitis: a real-world study. Chiricozzi, A., Dal Bello, G., Gori, N., et al.[2023]

In a phase III study involving 165 adult Chinese patients with moderate-to-severe atopic dermatitis, dupilumab significantly improved skin condition, with 26.8% of patients achieving the primary efficacy endpoint compared to only 4.8% in the placebo group (P < 0.001).

Dupilumab demonstrated a favorable safety profile, although there was a higher incidence of conjunctivitis and injection site reactions compared to placebo, indicating that while effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of dupilumab in Chinese patients with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled study. Zhao, Y., Wu, L., Lu, Q., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

[Dupilumab: beyond atopic dermatitis, off-label use in dermatology]. [2023]

3. 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]

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

Dupilumab: First Global Approval. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

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

New Indication for Dupilumab. [2022]

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

Identification of clinical predictors for dupilumab dose spacing in adults with atopic dermatitis: a real-world study. [2023]

9. England pubmed.ncbi.nlm.nih.gov

The efficacy and safety of dupilumab in Chinese patients with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled study. [2022]