A Phase 2 Study of Barzolvolimab in Patients With Eosinophilic Esophagitis

Overview

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

Full Title of Study: “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)”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Study Primary Completion Date: March 2025

Detailed Description

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

Interventions

• Biological: barzolvolimab
  • subcutaneous administration
• Drug: Matching Placebo
  • subcutaneous administration

Arms, Groups and Cohorts

• Active Comparator: Barzolvolimab (CDX-0159)
  • 300 mg subcutaneous administration every 8 weeks through week 24
• Placebo Comparator: Placebo then barzolvolimab (CDX-0159) 300mg
  • Matching placebo subcutaneous administration every 8 weeks through week 16, then 300mg subcutaneous administration every 8 weeks through week 24

Clinical Trial Outcome Measures

Primary Measures

• Absolute change from baseline to Week 12 in peak intraepithelial mast cell (PMC) count (PMC/hpf).
  • Time Frame: From baseline to Visit 6 (Week 12)
  • 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.

Secondary Measures

• Absolute changes from baseline to Week 12 in Dysphagia Symptom Questionnaire (DSQ).
  • Time Frame: From baseline to Visit 6 (Week 12)
  • DSQ is a validated daily patient-reported outcome to specifically measure the frequency and severity of dysphagia symptoms associated with eosinophilic esophagitis.
• Absolute change from baseline to Week 12 in peak intraepithelial mast cell (PMC) count (PMC/hpf) among patients with baseline PMC ≥ 12/hpf.
  • Time Frame: From baseline to Visit 6 (Week 12)
  • 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.
• Absolute change from baseline to Week 12 in Peak esophageal intraepithelial eosinophil count (PEC) (PEC/hpf).
  • Time Frame: From baseline to Visit 6 (Week 12)
  • 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.
• Percent (%) change from baseline to Week 12 in PMC/hpf.
  • Time Frame: From baseline to Visit 6 (Week 12)
  • 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.
• Incidence of Treatment Emergent Adverse Events.
  • Time Frame: From first dose through Visit 14 (Week 44)
  • The rates of treatment emergent adverse events will be summarized.

Participating in This Clinical Trial

Key Inclusion Criteria 1. ≥ 18 years of age 2. Documented diagnosis of eosinophilic esophagitis (EoE) by endoscopy 3. 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 4. 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 5. On a stable diet which includes solid foods for ≥ 2 months prior to Screening (and throughout the study) 6. 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) 7. Willing to be compliant with completion of daily questionnaire Key Exclusion Criteria 1. Diagnosed with hypereosinophilic syndrome or Churg-Strauss syndrome (eosinophilic granulomatosis with polyangiitis) 2. History of clinicopathologic diagnosis of eosinophilic gastritis or eosinophilic duodenitis 3. Known active Helicobacter pylori infection 4. History of coagulation disorders, esophageal varices, achalasia, Crohn's disease, ulcerative colitis, or celiac disease 5. Esophageal dilation within 3 months prior to Screening 6. Prior esophageal or gastric surgery that would confound the assessments of EoE 7. 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 8. Avoiding solid foods or using a feeding tube 9. Regular use of antiplatelet and/or anticoagulant therapy 10. 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 11. 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 12. Oral immunotherapy (OIT) within 6 months prior to Screening 13. 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 14. 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). 15. 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 16. Prior receipt of barzolvolimab There may be additional criteria your study doctor will review with you to confirm eligibility

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Celldex Therapeutics
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Contact(s)
  • Celldex Therapeutics, 844-723-9363, info@celldex.com