A Placebo-Controlled Study to Assess the Efficacy and Safety of Barzolvolimab (CDX-0159) in Adults with Active Eosinophilic Esophagitis (The "EvolvE" Study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Celldex Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

28 Sep 2023 → 17 Sep 2025

Decision date (initial)

2024-07-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Celldex Therapeutics, Inc.

External identifiers

EU CT number

2024-512767-30-00

EudraCT number

2022-001786-12

WHO UTN

U1111-1308-0346

ClinicalTrials.gov

NCT05774184

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacodynamic, Safety, Pharmacokinetic, Efficacy

To evaluate efficacy of barzolvolimab, compared to placebo, in reducing esophageal intraepithelial infiltration of mast cells as assessed by peak esophageal intraepithelial mast cell (PMC) count in EoE patients

Secondary objectives 3

1. 1 - To evaluate the efficacy of barzolvolimab, compared to placebo, in reducing symptoms of dysphagia as assessed by dysphagia symptom questionnaire (DSQ) in EoE patients
2. 2- To evaluate efficacy of barzolvolimab, compared to placebo, in reducing esophageal intraepithelial infiltration of eosinophils as assessed by peak esophageal intraepithelial eosinophil (PEC) count in EoE patients
3. 3 - To evaluate the safety profile of barzolvolimab in EoE patients

Conditions and MedDRA coding

Eosinophilic Esophagitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1 - Read, understood, and provided written informed consent, after the nature of the study has been fully explained.
2. 2 - Male or female, ≥ 18 years of age at the time of signing the informed consent
3. 3 - Documented diagnosis of EoE by endoscopy consent
4. 4 - Esophageal intraepithelial eosinophilic infiltration, with 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 at the Screening/Baseline esophagogastroduodenoscopy (EGD) at the Screening Visit.
5. 5 - Must be symptomatic, defined as: a. History (by patient report) of an average of at least 2 days per week with dysphagia with intake of solid foods during 1 month prior to the Screening Visit and b. At least 4 days with dysphagia (answer of "Yes" to DSQ Question #2) within the last 2 weeks immediately prior to randomization.
6. 6 - Must have been on a stable diet which includes solid foods for at least 2 months prior to the Screening Visit and throughout the study. Note: Stable diet is defined as no initiation or elimination of single or multiple food groups or reintroduction of previously eliminated food groups.
7. 7 - Have had 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) based on the investigator's clinical judgment.

Exclusion criteria 11

1. 1 - Diagnosis of hypereosinophilic syndrome or Churg-Strauss syndrome (or eosinophilic granulomatosis with polyangiitis).
2. 2 - History of a clinicopathologic diagnosis of eosinophilic gastritis or eosinophilic duodenitis.
3. 3 - Known active Helicobacter pylori infection
4. 4 - History of coagulation disorders or esophageal varices
5. 5 - History of achalasia, Crohn's disease, ulcerative colitis or celiac disease
6. 6 - Esophageal dilation within 3 months prior to the Screening Visit or a planned/elective esophageal dilation anytime during the study.
7. 7 - Avoiding solid foods or using feeding tube
8. 8 - Non-biologic systemic (oral or injectable) agents within 4 weeks or 5 half-lives, whichever is longer, prior to the Screening Visit.
9. 9 - Biologic therapy within 5 half-lives (or detectable serum level), prior to the Screening Visit. Note: Biologic agents include but are not limited to interleukin (IL)-4 receptor inhibitor (dupilumab), IL-5 inhibitors (e.g., mepolizumab, benralizumab), IL-13 inhibitors (e.g., tralokinumab, lebrikizumab), antiIgE (e.g., omalizumab), IFN-γ inhibitors, or other approved or investigational biologics.
10. 10 - 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; or any known contraindications or hypersensitivity to any component of study treatments, drugs of similar chemical classes (i.e., to murine, chimeric or human antibodies) or antihistamines.
11. 11 - Women who are pregnant or nursing. All female patients with reproductive potential must have a negative pregnancy test prior to starting study treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Absolute change from baseline to Week 12 in the PMC/high power field (hpf)

Secondary endpoints 5

1. 1 - Absolute changes from baseline to Week 12 in DSQ
2. 2 - Absolute change from baseline to Week 12 in PMC/hpf among patients with baseline PMC ≥ 12/hpf
3. 3 - Absolute change from baseline to Week 12 in PEC/hpf
4. 4 - Percent (%) change from baseline to week 12 in PMC/hpf
5. 5 - Incidence of TEAEs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Celldex Therapeutics Inc.

Sponsor organisation

Celldex Therapeutics Inc.

Address

53 Frontage Road Suite 220

City

Hampton

Postcode

08827-4034

Country

United States

Scientific contact point

Organisation

Celldex Therapeutics Inc.

Contact name

Science Department

Public contact point

Organisation

Celldex Therapeutics Inc.

Contact name

Clinical Development

Third parties 8

Locations

4 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications