Barzolvolimab for Eosinophilic Esophagitis
(EvolvE Trial)
Recruiting in Palo Alto (17 mi)
+54 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Celldex Therapeutics
Must not be taking: Anticoagulants, Corticosteroids, Biologics, others
Disqualifiers: Hypereosinophilic syndrome, Crohn's, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing a medication called barzolvolimab. It aims to help adult patients with Eosinophilic Esophagitis, a condition affecting the esophagus. The study will check if barzolvolimab can reduce inflammation and improve symptoms.
Will I have to stop taking my current medications?
The trial requires that you stop taking certain medications before joining. Specifically, you must not have used non-biologic systemic agents like corticosteroids or immunosuppressants within 2 months before screening, and biologic therapies must be stopped for a period based on their half-lives. Please discuss your current medications with the study doctor to see if they are allowed.
What data supports the effectiveness of the drug barzolvolimab for eosinophilic esophagitis?
While there is no direct data on barzolvolimab for eosinophilic esophagitis, similar treatments like dupilumab, which target specific immune pathways, have shown promise in treating this condition by improving symptoms and reducing inflammation.
12345How is the drug barzolvolimab different from other treatments for eosinophilic esophagitis?
Barzolvolimab is unique because it is an anti-KIT monoclonal antibody, which means it targets a specific protein involved in immune responses, potentially offering a novel approach for treating eosinophilic esophagitis, a condition with limited standard treatment options.
678910Eligibility Criteria
Adults with Eosinophilic Esophagitis who experience swallowing difficulties at least twice a week, have not responded well to standard treatments, and can complete daily questionnaires. They must not have certain other digestive or allergic conditions, recent esophageal procedures, or be on specific medications.Inclusion Criteria
Standard treatments for my EoE did not work or were not suitable for me.
On a stable diet which includes solid foods for ≥ 2 months prior to Screening (and throughout the study)
Willing to be compliant with completion of daily questionnaire
+1 more
Exclusion Criteria
I have not had oral immunotherapy in the last 6 months.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive 300 mg of barzolvolimab or placebo subcutaneously every 4 weeks
24 weeks
6 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
20 weeks
8 visits (in-person)
Participant Groups
The trial is testing the effectiveness and safety of barzolvolimab compared to a placebo in treating adults with Eosinophilic Esophagitis. Participants will receive either the actual drug or a placebo without knowing which one they are getting.
2Treatment groups
Active Control
Placebo Group
Group I: Barzolvolimab (CDX-0159)Active Control1 Intervention
300 mg subcutaneous administration every 4 weeks through week 24
Group II: Placebo then barzolvolimab (CDX-0159) 300mgPlacebo Group1 Intervention
Matching placebo subcutaneous administration every 4 weeks through week 16, then 300mg subcutaneous administration every 4 weeks through week 24
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of North Carolina (UNC) HospitalsChapel Hill, NC
Duke University Medical CenterDurham, NC
The Clinical Trials Network, LLCWilloughby, OH
Connecticut Clinical Research Institute, LLCBristol, CT
More Trial Locations
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Who Is Running the Clinical Trial?
Celldex TherapeuticsLead Sponsor
References
Scientific journey to the first FDA-approved drug for eosinophilic esophagitis. [2023]When eosinophilia was first associated with esophagitis, it was thought to reflect gastroesophageal reflux disease, especially given the efficacy of reflux medications to abate esophageal eosinophilia in many individuals. Subsequent studies demonstrated disease remittance with amino acid-based formulas and conversely induction of esophageal eosinophilia in mice following allergen challenge. These results, along with the finding that proton pump inhibitors alleviated esophageal eosinophilia by an anti-inflammatory mechanism, turned attention away from an acid-induced pathogenesis and established eosinophilic esophagitis (EoE) as a separate disease entity driven by allergic inflammation. The disease underpinnings were elucidated by analysis of esophageal transcriptomic profiling, revealing gene signatures orchestrated by type 2 cytokine signaling, mainly IL-13. Preclinical studies showed that IL-13 overproduction was sufficient to induce EoE-like changes in mice and human ex vivo systems and conversely that inhibiting IL-13 signaling attenuated these processes. An early proof-of-principle study with a humanized anti-IL-13 mAb in patients with EoE revealed correction of the EoE transcriptome and attenuation of esophageal eosinophilia, providing a rationale for advancing anti-type 2 cytokine therapy for EoE. Dupilumab, a precision therapeutic mAb that blocks the shared IL-13 and IL-4 receptor, is the first drug to advance through clinical trials and receive US Food and Drug Administration approval for EoE. The ability of dupilumab to improve clinical, histologic, endoscopic, and molecular features of EoE and garner US Food and Drug Administration approval is a victory for science, rare diseases, patients, and advocacy and provides a framework for developing additional EoE treatments and approved treatments for eosinophilic gastrointestinal disease beyond the esophagus.
Biological therapies for eosinophilic gastrointestinal diseases. [2019]The scientific basis and the clinical application of mAb therapies that target specific immunologic pathways for eosinophilic gastrointestinal diseases are areas of active interest. There is a growing recognition of a subset of patients with eosinophilic esophagitis whose disease does not respond well to topical steroids or elimination diets. In addition, long-term use of corticosteroids presents possible risks that are currently being evaluated. Systemic therapy with a biologic agent offers potential advantages as a global approach that could limit the need for multiple, locally active medical therapies and allergen avoidance. The identification of novel biologic strategies is ongoing, and the recent validation of instruments and outcome measures to assess disease activity has proved essential in demonstrating efficacy. Studies using biologics that target IL-13 pathways in the treatment of eosinophilic esophagitis have demonstrated substantial promise.
Approaches and Challenges to Management of Pediatric and Adult Patients With Eosinophilic Esophagitis. [2022]Treatment of eosinophilic esophagitis has progressed from elemental formula for children and esophageal dilation for adults to selective exclusion of food triggers and swallowed topical corticosteroids. Management guidelines are available from the American Gastroenterological Association and the Joint Task Force on Allergy Immunology Practice Parameters. We cannot, however, evaluate the efficacy of treatments without a definition of response. We propose a treat-to-target approach, based on symptoms and findings from endoscopy and histology. This approach addresses dissociations between outcomes, such as symptom persistence despite normalization of histologic features and symptom resolution after esophageal dilation despite histologic features of active disease. Eosinophilic esophagitis can now be treated with biologic agents that target specific immune pathways, and findings from prospective trials have indicated that less-restrictive, empiric, elimination diets can be effective and reduce the need for repeated endoscopic assessment of disease activity during food reintroduction. We also discuss eosinophilic esophagitis subtypes, factors associated with disease, and advances in management.
Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis. [2023]Dupilumab, a fully human monoclonal antibody, blocks interleukin-4 and interleukin-13 signaling, which have key roles in eosinophilic esophagitis.
A pilot study of omalizumab in eosinophilic esophagitis. [2018]Eosinophilic disorders of the gastrointestinal tract are an emerging subset of immune pathologies within the spectrum of allergic inflammation. Eosinophilic Esophagitis (EoE), once considered a rare disease, is increasing in incidence, with a rate of over 1 in 10,000 in the US, for unknown reasons. The clinical management of EoE is challenging, thus there is an urgent need for understanding the etiology and pathophysiology of this eosinophilic disease to develop better therapeutic approaches. In this open label, single arm, unblinded study, we evaluated the effects of an anti-IgE treatment, omalizumab, on local inflammation in the esophagus and clinical correlates in patients with EoE. Omalizumab was administered for 12 weeks to 15 subjects with long standing EoE. There were no serious side effects from the treatment. Esophageal tissue inflammation was assessed both before and after therapy. After 3 months on omalizumab, although tissue Immunoglobulin E (IgE) levels were significantly reduced in all but two of the subjects, we found that full remission of EoE, which is defined as histologic and clinical improvement only in 33% of the patients. The decrease in tryptase-positive cells and eosinophils correlated significantly with the clinical outcome as measured by improvement in endoscopy and symptom scores, respectively. Omalizumab-induced remission of EoE was limited to subjects with low peripheral blood absolute eosinophil counts. These findings demonstrate that in a subset of EoE patients, IgE plays a role in the pathophysiology of the disease and that anti-IgE therapy with omalizumab may result in disease remission. Since this study is open label there is the potential for bias, hence the need for a larger double blind placebo controlled study. The data presented in this pilot study provides a foundation for proper patient selection to maximize clinical efficacy.
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.
Nimotuzumab in the Treatment of Inoperable Esophageal Tumors of Epithelial Origin. [2022]Label="Background" NlmCategory="UNASSIGNED">Nimotuzumab is a humanized monoclonal antibody that targets the epidermal growth factor receptor. It was approved in Cuba for the indication of inoperable malignant tumors of the esophagus of epithelial origin. The purpose of this study was to evaluate the safety, overall and progression-free survival, clinical response, and quality of life, in adult patients with inoperable esophageal tumors of epithelial origin treated with nimotuzumab in a practical context. Material and Methods. The number of patients who developed adverse events was determined, and the frequency, seriousness, causality, and severity of these adverse events were determined. It also determined the median of survival and progression-free survival and rates at 12 and 24 months and the quality of life.
Severe Ulcerative Esophagitis Induced by Crizotinib Therapy. [2020]Crizotinib is an oral tyrosine-kinase inhibitor that inhibits anaplastic lymphoma kinase (ALK) in gene-rearranged non-small cell lung cancer (NSCLC). In 2011, the Food and Drug Administration approved crizotinib for treatment of locally advanced or metastatic ALK-positive NSCLC. The crizotinib adverse events profile included esophageal disorders in 11% of patients treated during trial phases I, II, and III, but none of them had severe events. We describe the development of severe ulcerative esophagitis secondary to crizotinib therapy and the re-introduction of therapy at a lower dose without recurrence of esophageal symptoms.
Ramucirumab: first global approval. [2023]Ramucirumab (Cyramza™ [US]), a fully human immunoglobulin G1 (IgG1) monoclonal antibody that inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), has been developed by Eli Lilly (formerly ImClone Systems) for the treatment of cancer. Ramucirumab has received its first global approval in the US for use as monotherapy in the treatment of advanced or metastatic gastric cancer or gastro-oesophageal junction adenocarcinoma in patients who experience disease progression on or after fluoropyrimidine- or platinum-containing chemotherapy. Ramucirumab is the first treatment to be approved by the US FDA for this setting. This article summarizes the milestones in the development of ramucirumab leading to this first approval for the treatment of gastric cancer and gastro-oesophageal junction adenocarcinoma.
A case of crizotinib-induced esophageal ulcers. [2020]We report a case of crizotinib-induced esophageal ulcers in a 45-year-old woman with metastatic anaplastic lymphoma kinase-positive non-small-cell lung cancer after 10 weeks of therapy. Endoscopic and pathologic findings were consistent with active inflammation with mid-esophageal ulceration and consistent with drug-induced esophagitis. Crizotinib was held and had a complete clinical and radiographic resolution of her symptoms. Patient was started on treatment with another anaplastic lymphoma kinase-targeted agent alectinib and has been tolerating it well without evidence of recurrence of esophagitis.