Dupilumab for Esophagitis
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Sanofi
Prior Safety Data
Breakthrough Therapy
Approved in 2 jurisdictions
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).
Is the drug Dupilumab a promising treatment for esophagitis?Yes, Dupilumab is a promising treatment for esophagitis. It has been approved to treat eosinophilic esophagitis in adults and children ages 12 and older, making it the first drug approved for this disease. This shows its potential in effectively managing the condition.356812
What safety data is available for Dupilumab?Dupilumab, also known as Dupixent, has been evaluated for safety in various conditions, including atopic dermatitis, asthma, and eosinophilic esophagitis. It generally has a favorable safety profile with few, reversible side effects. However, there are reports of ocular adverse reactions that require prompt management. In asthma patients, Dupilumab was found to be generally safe with no significant difference in adverse events compared to placebo, although it was associated with increased blood eosinophils. The LIBERTY EoE TREET study also assessed its long-term safety in eosinophilic esophagitis.39101113
Do I need to stop my current medications to join the trial?The trial requires that you stop taking swallowed topical corticosteroids at least 8 weeks before starting. Other medications are not specifically mentioned, so check with the trial team for more details.
What data supports the idea that Dupilumab for Esophagitis is an effective drug?The available research does not provide any data on Dupilumab for Esophagitis. Instead, it focuses on other treatments for different types of esophageal and gastric cancers, such as Ramucirumab and Durvalumab. Therefore, there is no information here to support the effectiveness of Dupilumab for Esophagitis.124714
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
I have had trouble swallowing solids at least twice a week in the last month.
I weigh at least 40 kg.
Exclusion Criteria
I do not have conditions like hypereosinophilic syndrome or Churg Strauss syndrome.
I have a history of specific digestive system conditions or surgeries.
I have a history of bleeding disorders or esophageal varices.
I have taken corticosteroids by mouth in the last 8 weeks.
I have been part of a dupilumab study or have used, or cannot use, dupilumab due to health reasons.
Treatment Details
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: DupilumabExperimental Treatment1 Intervention
Subcutaneous injection (SC) as per protocol
Group II: PlaceboPlacebo Group1 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
University of North Carolina School of Medicine Site Number : 8400007Chapel Hill, NC
Investigational Site Number : 1240004Vancouver, Canada
Cleveland Clinic - Cleveland- Site Number : 8400009Cleveland, OH
Investigational Site Number : 1240002Montreal, Canada
More Trial Locations
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Who is running the clinical trial?
SanofiLead Sponsor
Regeneron PharmaceuticalsIndustry Sponsor
References
Ramucirumab as second-line treatment for patients with metastatic esophagogastric adenocarcinoma. [2023]Ramucirumab is a fully humanized monoclonal antibody targeting the extracellular domain of the VEGF receptor 2. It prevents ligand binding to VEGF receptor 2 and receptor-mediated pathway activation in endothelial cells. After promising Phase I trial results in a variety of tumor types, two pivotal placebo-controlled Phase III trials conducted in patients with pretreated metastatic esophagogastric adenocarcinoma demonstrated significant clinical activity regarding the prolongation of overall survival both as monotherapy (REGARD study) and in combination with paclitaxel (RAINBOW study). Currently, ramucirumab is being investigated in the first-line treatment of esophagogastric adenocarcinoma in combination with capecitabine and cisplatin in a Phase III trial (RAINFALL).
[Ramucirumab - a new anticancer agent]. [2023]Ramucirumab is a humanized monoclonal antibody against vascular endothelial growth factor receptor-2, which inhibits the binding of vascular endothelial growth factor-A, -C and -D ligands. Furthermore it blocks the ligand stimulated activation of p44/p42 mitogen activated protein kinases, thus neutralizing the ligand induced proliferation and migration of human endothelial cells. Based on the results of the REGARD (Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma) and the RAINBOW (Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma) studies ramucirumab was approved for 2nd line treatment as monotherapy and in combination with paclitaxel for patients with local relapse and unresectable or metastatic gastric cancer (including gastro-esophegal junction adenocarcinoma). Based on the results, in advanced solid malignancies, ramucirumab may prolong progression free survival and overall survival, although it may increase the risk of all adverse events (fatigue, neutropenia, haemorrhage, nausea, stomatitis). The authors review the clinical studies of ramucirumab. Orv. Hetil., 2016, 157(40), 1587-1594.
Dupilumab: First Global Approval. [2022]Dupilumab (Dupixent®) is a fully human monoclonal antibody directed against the interleukin (IL)-4 receptor α (IL-4Rα) subunit. Dupilumab inhibits the signalling of the type 2 cytokines IL-4 and IL-13 and was co-developed by Regeneron Pharmaceuticals and Sanofi as a potential therapeutic agent for the treatment of atopic or allergic diseases. In March 2017 dupilumab received its first global approval, in the USA, for use in the treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. Dupilumab is in preregistration for this indication in the EU. In addition, dupilumab is currently under phase III development across the world for the treatment of asthma and nasal polyposis as well as for atopic dermatitis in paediatric patients. The agent has also entered phase II development in the USA for the treatment of eosinophilic oesophagitis. This article summarizes the milestones in the development of dupilumab leading to this first approval for the treatment of moderate-to-severe atopic dermatitis in adults.
Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020]Biologic agents, including targeted antibodies as well as immunomodulators, are demonstrating unparalleled development and study across the entire spectrum of human malignancy. This review summarizes the current state of biologic therapies for esophageal, esophagogastric, and gastric malignancies, including those that target human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), c-Met, mechanistic target of rapamycin (mTOR) and immunomodulators. We focus primarily on agents that have been included in phase II and III clinical trials in locally advanced, progressive, or metastatic esophageal and gastric malignancies. At this time, only two biologic therapies are recommended by the National Comprehensive Cancer Network (NCCN): trastuzumab for patients with esophageal/esophagogastric or gastric adenocarcinomas with HER2 overexpression and ramucirumab, a VEGFR-2 inhibitor, as a second-line therapy for metastatic disease. However, recent reports of increases in overall and progression-free survival for agents including pertuzumab, apatinib, and pembrolizumab will likely increase the use of targeted biologic therapy in clinical practice for esophageal and gastric malignancies.
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.
The efficacy and safety of dupilumab in Chinese patients with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled study. [2022]Dupilumab is an antibody against interleukin-4 receptor α, used in the treatment of atopic dermatitis (AD).
Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. [2022]Label="PURPOSE">The phase III PACIFIC trial compared durvalumab with placebo in patients with unresectable, stage III non-small-cell lung cancer and no disease progression after concurrent chemoradiotherapy. Consolidation durvalumab was associated with significant improvements in the primary end points of overall survival (OS; stratified hazard ratio [HR], 0.68; 95% CI, 0.53 to 0.87; P = .00251) and progression-free survival (PFS [blinded independent central review; RECIST v1.1]; stratified HR, 0.52; 95% CI, 0.42 to 0.65; P < .0001), with manageable safety. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned.
New Indication for Dupilumab. [2022]Dupilumab (Dupixent) has been approved to treat eosinophilic esophagitis in adults and children ages 12 years and older who weigh at least 40 kilograms. This is the first drug approved to treat this disease.
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.
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.
[Dupilumab: beyond atopic dermatitis, off-label use in dermatology]. [2023]Dupilumab is a humanized IgG4 monoclonal antibody that targets the IL-4 receptor inhibiting the signaling of interleukin-4 and interleukin-13, two major cytokines in type 2 inflammatory diseases such as atopic dermatitis, asthma and nasosinusal polyposis. Since its approval for atopic dermatitis in 2017, the molecule has occasionally been used off-label in several dermatological conditions where standard treatments are often disappointing.Furthermore, what emerges from the data currently in the literature is a favourable safety profile with few, reversible side effects.
Identification of clinical predictors for dupilumab dose spacing in adults with atopic dermatitis: a real-world study. [2023]Dupilumab is a monoclonal antibody against the IL-4/IL-13 receptor-subunit approved for the treatment of moderate-severe atopic dermatitis (AD). Some attempts to increase dose interval have been described in both trial and real-world settings.
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]Long-term management options that specifically target the underlying inflammation in eosinophilic oesophagitis are needed. Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13; we aimed to assess its long-term efficacy and safety in adults and adolescents with eosinophilic oesophagitis enrolled in part B of the LIBERTY EoE TREET study who continued to part C (part B-C).
Association of Radiochemotherapy to Immunotherapy in unresectable locally advanced Oesophageal carciNoma-randomized phase 2 trial ARION UCGI 33/PRODIGE 67: the study protocol. [2023]In case of locally advanced and/or non-metastatic unresectable esophageal cancer, definitive chemoradiotherapy (CRT) delivering 50 Gy in 25 daily fractions in combination with platinum-based regimen remains the standard of care resulting in a 2-year disease-free survival of 25% which deserves to be associated with new systemic strategies. In recent years, several immune checkpoint inhibitors (anti-PD1/anti-PD-L1, anti-Program-Death 1/anti-Program-Death ligand 1) have been approved for the treatment of various solid malignancies including metastatic esophageal cancer. As such, we hypothesized that the addition of an anti-PD-L1 to CRT would provide clinical benefit for patients with locally advanced oesophageal cancer. To assess the efficacy of the anti-PD-L1 durvalumab in combination with CRT and then as maintenance therapy we designed the randomized phase II ARION (Association of Radiochemotherapy with Immunotherapy in unresectable Oesophageal carciNoma- UCGI 33/PRODIGE 67).