A Study of CDX-0159 in Patients With Eosinophilic Esophagitis

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of barzolvolimab in adult Eosinophilic Esophagitis patients.

Detailed Description
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The purpose of this study is to assess the efficacy and safety of barzolvolimab in adult Eosinophilic Esophagitis patients.

Official Title
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A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Barzolvolimab (CDX-0159) in Adults With Active Eosinophilic Esophagitis (The EvolvE Study)

Conditions
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Eosinophilic Esophagitis

Intervention / Treatment
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* Biological: barzolvolimab
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria ≥ 18 years of age Documented diagnosis of eosinophilic esophagitis (EoE) by endoscopy Peak esophageal intraepithelial eosinophil count (PEC) of ≥ 15 per high power field (hpf) from at least 2 of 3 levels (proximal, mid, and distal) of the esophagus Symptomatic, defined as • Average of ≥ 2 days per week with dysphagia with solid food intake in the 1 month prior to Screening, and • ≥ 4 days with dysphagia within the last 2 weeks prior to randomization On a stable diet which includes solid foods for ≥ 2 months prior to Screening (and throughout the study) Inadequate response to or is inappropriate for and/or intolerant to a standard-of-care treatment for EoE (e.g., PPI, swallowed topical corticosteroids, or dietary elimination) Willing to be compliant with completion of daily questionnaire Key Exclusion Criteria Diagnosed with hypereosinophilic syndrome or Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis) History of clinicopathologic diagnosis of eosinophilic gastritis or eosinophilic duodenitis Known active Helicobacter pylori infection History of coagulation disorders, esophageal varices, achalasia, Crohn's disease, ulcerative colitis, or celiac disease Esophageal dilation within 3 months prior to Screening Prior esophageal or gastric surgery that would confound the assessments of EoE Esophageal stricture that is difficult to pass with a standard adult upper endoscope (9 to 10 mm) or stricture that requires dilation at the Screening EGD Avoiding solid foods or using a feeding tube Regular use of antiplatelet and/or anticoagulant therapy Non-biologic systemic agents within 2 months prior to Screening, including but not limited to corticosteroid (oral, swallowed topical or parenteral), non-steroidal immunosuppressants (e.g., methotrexate, cyclosporin, tacrolimus, mycophenolate mofetil, azathioprine), other immunomodulators (e.g., Jak inhibitors, tyrosine kinase inhibitors), and investigational agents Biologic therapy within 3 months or 5 half-lives (whichever is shorter) prior to Screening, including but not limited to interleukin (IL)-4 receptor inhibitor (dupilumab), IL-5 inhibitors (e.g., mepolizumab, benralizumab), IL-13 inhibitors (e.g., tralokinumab, lebrikizumab), anti-IgE (e.g., omalizumab), IFN-γ inhibitors, or other approved or investigational biologics Oral immunotherapy (OIT) within 6 months prior to Screening Sublingual immunotherapy (SLIT) and/or subcutaneous immunotherapy (SCIT) Note: Not exclusionary if patient has been on a stable maintenance dose for at least 6 months prior to Screening Receipt of a live vaccine within 2 months prior to the Baseline (Day 1) Visit (patients must agree to avoid live vaccination during study treatment and within 3 months thereafter). Diagnosis of idiopathic anaphylaxis or other severe allergic reactions that in the opinion of the investigator, could increase the patient's risk for systemic hypersensitivity reactions Prior receipt of barzolvolimab There may be additional criteria your study doctor will review with you to confirm eligibility

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Barzolvolimab (CDX-0159)<br>300 mg subcutaneous administration every 8 weeks through week 24 | Biological: barzolvolimab<br>* subcutaneous administration<br>|
| Placebo Comparator: Placebo then barzolvolimab (CDX-0159) 300mg<br>Matching placebo subcutaneous administration every 8 weeks through week 16, then 300mg subcutaneous administration every 8 weeks through week 24 | Drug: Matching Placebo<br>* subcutaneous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change from baseline to Week 12 in peak intraepithelial mast cell (PMC) count (PMC/hpf). | Peak esophageal intraepithelial mast cell counts will be determined by counting mast cells in the most inflamed high-power field (hpf) of each of the 3 esophageal (proximal, mid, distal) levels and reported as mast cells/hpf. | From baseline to Visit 6 (Week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute changes from baseline to Week 12 in Dysphagia Symptom Questionnaire (DSQ). | DSQ is a questionnaire designed to measure difficulty swallowing associated with Eosinophilic Esophagitis (EoE), with total scores ranging from 0 to 84; higher DSQ scores indicate worse symptoms. | From baseline to Visit 6 (Week 12) | 
| Absolute change from baseline to Week 12 in peak intraepithelial mast cell (PMC) count (PMC/hpf) among patients with baseline PMC ≥ 12/hpf. | Peak esophageal intraepithelial mast cell counts will be determined by counting mast cells in the most inflamed high-power field (hpf) of each of the 3 esophageal (proximal, mid, distal) levels and reported as mast cells/hpf. | From baseline to Visit 6 (Week 12) | 
| Absolute change from baseline to Week 12 in Peak esophageal intraepithelial eosinophil count (PEC) (PEC/hpf). | Peak esophageal intraepithelial eosinophils will be determined by counting eosinophils in the most inflamed high-power field (hpf) of each of the 3 esophageal (proximal, mid, distal) levels and reported as eosinophils/hpf. | From baseline to Visit 6 (Week 12) | 
| Percent (%) change from baseline to Week 12 in PMC/hpf. | Peak esophageal intraepithelial mast cell counts will be determined by counting mast cells in the most inflamed high-power field (hpf) of each of the 3 esophageal (proximal, mid, distal) levels and reported as mast cells/hpf. | From baseline to Visit 6 (Week 12) | 
| Incidence of Treatment Emergent Adverse Events. | The rates of treatment emergent adverse events will be summarized. | From first dose through Visit 14 (Week 44) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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barzolvolimab, esophagitis, EoE, mast cells, CDX-0159