EvolvE: A Phase 2 Study of Barzolvolimab in Patients With Eosinophilic Esophagitis

Sponsor

Celldex Therapeutics (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05774184

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Eosinophilic Esophagitis	Biological: barzolvolimab Drug: Matching Placebo	Phase 2

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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)

Anticipated Study Start Date :

May 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Aug 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Barzolvolimab (CDX-0159) 300 mg subcutaneous administration every 8 weeks through week 24	Biological: barzolvolimab subcutaneous administration
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	Drug: Matching Placebo subcutaneous administration

Arm

Intervention/Treatment

Active Comparator: Barzolvolimab (CDX-0159)

300 mg subcutaneous administration every 8 weeks through week 24

Biological: barzolvolimab

subcutaneous administration

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

Drug: Matching Placebo

subcutaneous administration

Outcome Measures

Primary Outcome Measures

Absolute change from baseline to Week 12 in peak intraepithelial mast cell (PMC) count (PMC/hpf). [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 Outcome Measures

Absolute changes from baseline to Week 12 in Dysphagia Symptom Questionnaire (DSQ). [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. [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). [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. [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. [From first dose through Visit 14 (Week 44)]
The rates of treatment emergent adverse events will be summarized.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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