Barzolvolimab for Eosinophilic Esophagitis

(EvolvE Trial)

Recruiting at 54 trial locations

Overseen By Celldex Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Celldex Therapeutics

Must not be taking: Anticoagulants, Corticosteroids, Biologics, others

Disqualifiers: Hypereosinophilic syndrome, Crohn's, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 14

Duration: 24 weeks

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of barzolvolimab, an anti-KIT monoclonal antibody, for adults with Eosinophilic Esophagitis (EoE). EoE is a condition where the esophagus becomes inflamed due to a high number of eosinophils, a type of white blood cell. The study will compare barzolvolimab to a placebo, a look-alike treatment with no active drug, to determine if it can reduce symptoms such as difficulty swallowing solid foods. Participants must have an EoE diagnosis and experience trouble swallowing solid food several days a week. Those who have tried other EoE treatments without success may find this trial suitable. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that barzolvolimab is likely to be safe for humans?

Research has shown that barzolvolimab is generally safe for patients. In a recent study, participants reported a good safety profile, with most experiencing no serious side effects. Barzolvolimab, a lab-made protein, treats eosinophilic esophagitis, a condition causing inflammation in the esophagus.

While some individuals might experience mild reactions, serious issues are rare. The study examined barzolvolimab's effects over 76 weeks and found it safe for patients. For those considering joining a trial, this data suggests barzolvolimab is generally safe for most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Eosinophilic Esophagitis?

Barzolvolimab stands out because it targets the body's mast cells, which are thought to play a significant role in eosinophilic esophagitis (EoE). Unlike standard treatments for EoE, such as dietary changes, proton pump inhibitors, or corticosteroids, barzolvolimab works by inhibiting the activity of a protein called KIT, which is crucial for mast cell function and survival. This novel approach could offer a more targeted treatment, potentially reducing inflammation more effectively and with fewer side effects compared to existing options. Researchers are excited about its potential to provide relief for patients who may not respond well to current therapies.

What evidence suggests that barzolvolimab might be an effective treatment for Eosinophilic Esophagitis?

Research has shown that barzolvolimab can significantly reduce certain immune cells, called mast cells, in the esophagus of people with eosinophilic esophagitis (EoE). These mast cells can cause inflammation and discomfort in EoE. However, despite this reduction, studies found that the treatment did not improve symptoms like trouble swallowing or visible signs of the disease compared to a placebo. This trial will compare barzolvolimab to a placebo, with some participants initially receiving a placebo before switching to barzolvolimab. Thus, while barzolvolimab affects mast cells, it might not effectively ease the symptoms of EoE. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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

Exclusion Criteria

I have not had oral immunotherapy in the last 6 months.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• barzolvolimab

Trial Overview 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.

How Is the Trial Designed?

Group I: Barzolvolimab (CDX-0159) Active Control 1 Intervention

300 mg subcutaneous administration every 4 weeks through week 24

Group II: Placebo then barzolvolimab (CDX-0159) 300mg Placebo Group 1 Intervention

Matching placebo subcutaneous administration every 4 weeks through week 16, then 300mg subcutaneous administration every 4 weeks through week 24

Who Is Running the Clinical Trial?

Celldex Therapeutics

Lead Sponsor

Trials

66

Recruited

5,900+

Anthony S. Marucci

Celldex Therapeutics

Chief Executive Officer since 2008

MBA from Columbia University, MHL from Brown University

Diane C. Young

Celldex Therapeutics

Chief Medical Officer since 2019

MD from Harvard Medical School, AB in Biochemical Sciences from Harvard University

Published Research Related to This Trial

Biologic therapies, particularly those targeting HER2 and VEGF, are showing promise in treating esophageal and gastric cancers, with trastuzumab and ramucirumab currently recommended by the NCCN for specific patient groups.

Recent studies indicate that other agents like pertuzumab, apatinib, and pembrolizumab may improve overall and progression-free survival, suggesting a growing role for targeted biologic therapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. Samson, P., Lockhart, AC.[2020]

Nimotuzumab, a monoclonal antibody targeting the epidermal growth factor receptor, was found to be safe for patients with inoperable esophageal tumors, with only 1.3% experiencing serious adverse events, mostly mild to moderate in severity.

Patients treated with nimotuzumab alongside chemotherapy and radiotherapy achieved a median overall survival of 12.2 months and a median progression-free survival of 7.8 months, indicating improved survival outcomes and quality of life compared to those not receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nimotuzumab in the Treatment of Inoperable Esophageal Tumors of Epithelial Origin. González Fernández, S., Amador García, Y., Boris Porras, LG., et al.[2022]

Ramucirumab is a fully human monoclonal antibody that targets and inhibits VEGFR-2, which plays a key role in cancer growth and progression.

It has received FDA approval as a monotherapy for advanced gastric cancer or gastro-oesophageal junction adenocarcinoma in patients who have not responded to previous chemotherapy, marking it as the first treatment approved for this specific condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ramucirumab: first global approval. Poole, RM., Vaidya, A.[2023]

In a phase 3 trial involving patients aged 12 and older, weekly administration of dupilumab led to histologic remission in 60% of patients, significantly outperforming placebo, which had only a 5% remission rate.

Dupilumab also improved symptoms of eosinophilic esophagitis, as indicated by a substantial reduction in Dysphagia Symptom Questionnaire scores compared to placebo, demonstrating its efficacy in both histological and symptomatic relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis. Dellon, ES., Rothenberg, ME., Collins, MH., et al.[2023]

Crizotinib is an effective oral medication for treating ALK-positive non-small cell lung cancer, approved by the FDA in 2011, which works by inhibiting the anaplastic lymphoma kinase.

While 11% of patients experienced esophageal disorders during trials, severe ulcerative esophagitis was rare; in one case, the therapy was successfully resumed at a lower dose without returning symptoms, suggesting a potential management strategy for this side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Ulcerative Esophagitis Induced by Crizotinib Therapy. Jalil, AA., Craig, J., Bajaj, R., et al.[2020]

Biologic therapies targeting specific immunologic pathways, particularly IL-13, show promise for treating eosinophilic esophagitis, especially in patients who do not respond to traditional treatments like steroids or elimination diets.

These systemic biologic agents may reduce the need for multiple local therapies and allergen avoidance, potentially offering a safer long-term treatment option compared to corticosteroids, which carry risks with prolonged use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapies for eosinophilic gastrointestinal diseases. Wechsler, JB., Hirano, I.[2019]

A 45-year-old woman developed esophageal ulcers after 10 weeks of crizotinib therapy for metastatic lung cancer, indicating a potential side effect of this medication.

After stopping crizotinib, the patient's symptoms completely resolved, and she successfully transitioned to alectinib without recurrence of esophagitis, suggesting that alternative treatments may be better tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of crizotinib-induced esophageal ulcers. Sussman, TA., Khunger, M., Velcheti, V.[2020]

Eosinophilic esophagitis treatment has evolved to include targeted therapies like biologic agents and less-restrictive elimination diets, which can effectively manage symptoms and reduce the need for frequent endoscopies.

A proposed 'treat-to-target' approach emphasizes the importance of defining treatment response based on both symptoms and endoscopic/histological findings, addressing the disconnect between symptom relief and disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaches and Challenges to Management of Pediatric and Adult Patients With Eosinophilic Esophagitis. Hirano, I., Furuta, GT.[2022]

In a pilot study of 15 patients with Eosinophilic Esophagitis (EoE), treatment with the anti-IgE drug omalizumab for 12 weeks significantly reduced tissue IgE levels and showed a correlation between decreased eosinophils and clinical improvement, although full remission was achieved in only 33% of patients.

The study suggests that omalizumab may be effective for EoE in patients with low peripheral blood eosinophil counts, highlighting the need for further research to confirm these findings in a larger, controlled trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of omalizumab in eosinophilic esophagitis. Loizou, D., Enav, B., Komlodi-Pasztor, E., et al.[2018]

Eosinophilic esophagitis (EoE) is now recognized as a distinct disease driven by allergic inflammation, particularly linked to IL-13 signaling, rather than being solely caused by acid reflux, as shown by various studies including transcriptomic profiling.

Dupilumab, an anti-IL-13 and IL-4 receptor monoclonal antibody, has been approved by the FDA for EoE, demonstrating significant improvements in clinical and molecular features of the disease, marking a significant advancement in treatment options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scientific journey to the first FDA-approved drug for eosinophilic esophagitis. Rothenberg, ME.[2023]

Citations

1. ir.celldex.com ir.celldex.com/news-releases/news-release-details/celldex-reports-results-phase-2-study-barzolvolimab-eosinophilic

Celldex Reports Barzolvolimab Phase 2 Study Results in EoE Study met primary endpoint demonstrating barzolvolimab's ability to potently deplete mast cells in the gastrointestinal tract ...

2. ir.celldex.com ir.celldex.com/news-releases/news-release-details/celldex-presents-histology-data-phase-2-study-barzolvolimab-eoe

Celldex: Barzolimab Phase 2 Data in EoE, Mast Depleting Agent Barzolvolimab has been shown to deplete cutaneous mast cells and we believe it will likely also deplete esophageal mast cells, which could lead ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05774184

NCT05774184 | A Study of CDX-0159 in Patients With ... The purpose of this study is to assess the efficacy and safety of barzolvolimab in adult Eosinophilic Esophagitis patients.

4. trial.medpath.com trial.medpath.com/news/259d24255f5fae2b/celldex-s-barzolvolimab-phase-2-trial-provides-key-insights-into-mast-cell-role-in-eosinophilic-esophagitis

Celldex's Barzolvolimab Phase 2 Trial Provides Key Insights ... Despite achieving a 65% reduction in esophageal mast cells, the treatment failed to improve clinical symptoms or endoscopic disease measures compared to placebo ...

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/celldex-drops-eoe-mab-despite-meeting-primary-endpoint/

Celldex drops EoE mAb despite meeting primary endpoint Barzolvolimab also fell short in improving other key symptoms of EoE – including swallowing difficulties, as there were no significant changes ...

6. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effectiveness-and-safety-of-barzolvolimab-in-adults-with-active-eosinophilic-esophagitis/

Study on the Effectiveness and Safety of Barzolvolimab in ... This clinical trial tests the safety and effectiveness of Barzolvolimab, a monoclonal antibody, in treating adults with active eosinophilic ...

7. ir.celldex.com ir.celldex.com/news-releases/news-release-details/celldex-presents-unprecedented-76-week-results-barzolvolimab

Celldex Presents Unprecedented 76 Week Results from ... Barzolvolimab demonstrated a well tolerated safety profile throughout the study. ... Barzolvolimab is a humanized monoclonal antibody that binds ...