Dupilumab vs Fluticasone for Esophagitis
(DeTECTS Trial)
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Colorado, Denver
Must not be taking: Dupilumab
Disqualifiers: Esophageal disease, IBD, liver disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
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.
12345Is 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.
14678How 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.
12345Eligibility 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.
+3 more
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.
+6 more
Trial 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
Participant Groups
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.
2Treatment groups
Active Control
Group I: dupilumab (also known as Dupixent)Active Control1 Intervention
Group II: fluticasone (also known as Flovent)Active Control1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Children's Hospital Colorado/University of Colorado School of MedicineAurora, CO
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Who Is Running the Clinical Trial?
University of Colorado, DenverLead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
References
Dupixent, a New Entrant In the Asthma Lists. [2019]Sanofi and Regeneron's Dupixent (dupilumab)-which is already approved for atopic dermatitis-has an FDA action date of October 20 for its asthma indication. It will join Nucala, (mepolizumab), Cinqair (reslizumab), and Fasenra (benralizumab) as a monoclonal antibody approved as a treatment for the type 2 inflammation phenotype in severe asthma.
Dupilumab: A Review in Chronic Rhinosinusitis with Nasal Polyps. [2022]Dupilumab (Dupixent®) is a fully human IgG4 monoclonal antibody against the interleukin (IL)-4 receptor α (IL-4Rα) subunit, which is shared by the type I IL-4 and the type II IL-4/IL-13 receptor complexes. By binding to and blocking this subunit, dupilumab inhibits IL-4 and IL-13, which are the major drivers of human type 2 inflammatory disease [e.g. asthma, atopic dermatitis and chronic rhinosinusitis with nasal polyps (CRSwNP)]. Dupilumab, administered subcutaneously, is the first biological therapy to be approved for the treatment of adults with inadequately controlled CRSwNP in the EU and the USA. In two placebo-controlled, multinational, phase III studies of 24 and 52 weeks' duration, the addition of dupilumab (300 mg every 2 weeks) to the intranasal corticosteroid treatment of adults with severe, inadequately controlled CRSwNP was generally well tolerated and improved nasal polyp size, sinus opacification and health-related quality of life (HR-QOL), relieved the major symptoms of CRSwNP (nasal congestion or obstruction, nasal discharge and loss of smell) and reduced the use of systemic corticosteroids and the need for nasal polyp surgery. Improvements in nasal polyp size, sinus opacification and nasal congestion or obstruction were achieved regardless of the presence of comorbid asthma or NSAID-exacerbated respiratory disease, or a history of previous nasal polyp surgery, with patients with comorbid asthma also demonstrating improvements in lung function and asthma control regardless of their baseline eosinophil count. Thus, add-on subcutaneous dupilumab is a valuable treatment option for adults with inadequately controlled CRSwNP.
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]Dupilumab is a humanized monoclonal antibody targeting the IL4/IL13 signaling pathway, already used for atopic dermatitis and chronic rhinitis with nasal polyps, recently approved for severe type-2 asthma. Its efficacy has been demonstrated in randomized control trials. The aim of our study is to evaluate possible early clinical improvement and type 2 biomarkers modifications in severe asthmatic patients treated with dupilumab in a real-life setting.
Dupilumab for the treatment of asthma. [2019]Dupilumab (REGN668/SAR231893), produced by a collaboration between Regeneron and Sanofi, is a monoclonal antibody currently in phase III for moderate-to-severe asthma. Dupilumab is directed against the α-subunit of the interleukin (IL)-4 receptor and blocks the IL-4 and IL-13 signal transduction. Areas covered: Pathophysiological role of IL-4 and IL-13 in asthma; mechanism of action of dupilumab; pharmacology of IL-4 receptor; phase I and phase II studies with dupilumab; regulatory affairs. Expert opinion: Patients with severe asthma who are not sufficiently controlled with standard-of-care represent the target asthma population for dupilumab. If confirmed, efficacy of dupilumab in both eosinophilic and non-eosinophilic severe asthma phenotype might represent an advantage over approved biologics for asthma, including omalizumab, mepolizumab, and reslizumab. Head-to-head studies to compare dupilumab versus other biologics with different mechanism of action are required. Pediatric studies with dupilumab are currently lacking and should be undertaken to assess efficacy and safety of this drug in children with severe asthma. The lack of preclinical data and published results of the completed four phase I studies precludes a complete assessment of the pharmacological profile of dupilumab. Dupilumab seems to be generally well tolerated, but large studies are required to establish its long-term safety and tolerability.
Improvement in eosinophilic esophagitis when using dupilumab for other indications or compassionate use. [2022]Dupilumab has been approved to treat atopic dermatitis, asthma, and nasal polyps and is in active clinical trials for the treatment of eosinophilic esophagitis (EoE). Given its shared immunopathology, we hypothesized that EoE symptoms and inflammation would improve when dupilumab therapy was used for other allergic indications.
Dupilumab efficacy and safety in patients with moderate to severe asthma: A systematic review and meta-analysis. [2022]Background: Dupilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-4 receptor and inhibits the signaling of IL-4 and IL-13. It is approved for treating asthma and other type-2 inflammatory diseases. There is a conflict in the literature regarding the safety and efficacy of dupilumab. Thus, we aimed to assess the safety and efficacy of dupilumab in patients with moderate to severe asthma. Methods: Six databases (PubMed, Embase, Scopus, Web of Science, Cochrane library, and clinicaltrials.gov registry) were searched until January 2022. We included randomized controlled trials that compared dupilumab with the placebo in moderate to severe asthma patients. We extracted the data at 12 and 24 weeks and analyzed them using review manager 5.4. Findings: Thirteen trials were included. Dupilumab significantly improved the forced expiratory volume in 1 s, asthma control questionnaire score, the fraction of exhaled nitric oxide level, and immunoglobulin E level at 12 and 24 weeks (p < 0.05). However, it was associated with increased blood eosinophils at 12 and 24 weeks. Dupilumab was generally a safe agent for asthmatic patients. It showed no significant difference compared with the placebo regarding most adverse events. Conclusion: Dupilumab improves pulmonary function and reduces local and systemic inflammatory markers with minimal adverse events in patients with moderate to severe asthma.
Dupilumab Efficacy in Patients Stratified by Baseline Treatment Intensity and Lung Function. [2022]Label="PURPOSE" NlmCategory="OBJECTIVE">The Phase 3 LIBERTY ASTHMA QUEST study in patients aged ≥12 years with uncontrolled, moderate-to-severe asthma demonstrated the efficacy and safety of dupilumab 200 mg and 300 mg every 2 weeks (q2w) vs matched placebo in the overall population. This post hoc analysis assessed dupilumab efficacy by disease severity as evidenced by baseline % predicted forced expiratory volume in 1 second (FEV1) and dose of inhaled corticosteroids (ICS).
Safety update: dupilumab and ocular adverse reactions. [2022]Overview of: Medicines and Healthcare products Regulatory Agency. Dupilumab (Dupixent▼): risk of ocular adverse reactions and need for prompt management. Drug Safety Update 2022;16(4): 1.