A Trial to Evaluate EP-104IAR in Adults With Eosinophilic Esophagitis (EoE).

Eosinophilic Esophagitis Clinical Trial

— RESOLVE  

Official title:

A Phase 1b, Open Label Trial Evaluating the Safety, Pharmacokinetics, and Efficacy of EP-104IAR in Adults With Eosinophilic Esophagitis (EoE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05608681
• Other study ID #: EP-104IAR-102
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 31, 2023
• Est. completion date: November 2024

Study information

• Verified date: November 2023
• Source: Eupraxia Pharmaceuticals Inc.
• Contact: Christine Dobek, MSc
• Phone: 778-873-8939
• Email: cdobek[@]eupraxiapharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

An open-label, dose-escalation study to explore the safety, tolerability and pharmacokinetics of EP-104IAR in adults with eosinophilic esophagitis (EoE). Endoscopic and histologic assessments will also be evaluated to understand the local effects of EP-104IAR on eosinophilic EoE disease activity.

The study will evaluate up to 8 doses of EP-104IAR (4 mg to 40 mg) in cohorts of 3 to 6 participants per cohort. If all planned cohorts are evaluated, or cohorts need to be repeated, up to 24 participants could be enrolled.

The study involves 7 site visits spread over approximately 32 weeks.

All participants will receive active study drug (EP-104IAR), The study drug will be administered by qualified personnel during an esophagogastroduodenoscopy (EGD) procedure at the Baseline/Dosing visit.

Safety will be assessed throughout the study. Blood and urine samples will be collected at site visits for laboratory assessments and to measure plasma levels of EP-104IAR.

Participants will complete questionnaires to assess symptoms of dysphagia and odynophagia and will undergo 3 EGDs with esophageal biopsies at the Baseline/Dosing Visit, and at 4 and 12 weeks post dose.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Symptomatic EoE;

• For women of childbearing potential, a negative pregnancy test and willing to use a highly effective method of birth control until end of study;

• Willing and able to adhere to study-related procedures and visit schedule;

• Willing and able to provide informed consent.

Exclusion Criteria:

• Concomitant esophageal disease, relevant GI disease, or any condition, history, or laboratory abnormality that might interfere with the study;

• Oral or esophageal mucosal infection of any type (bacterial, viral, or fungal);

• Oropharyngeal or dental conditions that prevents normal eating;

• Severe esophageal motility disorders other than EoE;

• Contraindication to or factors that substantially increase risks associated with EGD or biopsy, or narrowing of the esophagus that precludes EGD with a standard 9-10 mm endoscope, stricture requiring dilation within 8 weeks prior to Screening, or the need for dilation prior to EGD at Baseline;

• Any condition for which the use of corticosteroids is contraindicated (Participants with well controlled non-insulin dependent diabetes are permitted);

• Active or quiescent systemic fungal, bacterial, viral, or parasitic infections, or ocular herpes simplex. Or recent use of IV or oral antibiotics;

• Hypersensitivity, or intolerance to corticosteroids, or to any of the ingredients in the investigational medicinal product;

• Recent use of disallowed medications, or unwillingness to not use disallowed medications during the study;

• Recent initiation of a elimination or elemental diet (dietary therapy must remain stable throughout the study);

• Morning serum cortisol level = 5 µg/dL (138 nmol/L);

• Clinically significant abnormal laboratory values;

• Recent or currently planned participation in another interventional trial ;

• Previous participation in this study and had received study treatment;

• Females who are pregnant, breastfeeding, or planning to become pregnant during the study;

• Malignancies or history of malignancy within prior 5 years, except for treated or excised non-metastatic BCC, SCC of the skin, or cervical carcinoma in situ;

• History of alcohol or drug abuse;

• Any other reason, that, in the Investigator's opinion, unfavorably alters participant risk, confounds results, or prevents the participant from complying with study requirements.

Related Conditions & MeSH terms

• Eosinophilic Esophagitis
• Esophagitis

Intervention

Drug:
• EP-104IAR
Long-acting fluticasone propionate for injection

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Canada	McGill University Health Center	Montréal	Quebec
Canada	G.I. Research Institute	Vancouver	British Columbia
Netherlands	Amsterdam UMC	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
Eupraxia Pharmaceuticals Inc.

Countries where clinical trial is conducted

Australia,  Canada,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment emergent adverse events (TEAEs)	TEAEs will be summarized by dose/cohort	12 weeks
Primary	Severity of treatment emergent adverse events (TEAEs)	TEAEs will be summarized by dose/cohort and severity (mild, moderate, severe).	12 weeks
Primary	Change from baseline in morning serum cortisol levels	Cortisol will be will be summarized by dose/cohort and over time and compared to pre-dose values. A prolonged and clinically significant reduction in cortisol may indicate adrenal insufficiency.	12 weeks
Primary	Plasma concentrations of fluticasone propionate	Plasma concentrations of fluticasone propionate over time will be used to calculate PK parameters for each dose/cohort.	12 weeks
Secondary	Peak eosinophil count (PEC)	Biopsy specimens will be used to evaluate peak eosinophil counts (PEC). A higher number of eosinophils indicates more severe histological disease.	4 weeks
Secondary	Peak eosinophil count (PEC)	Biopsy specimens will be used to evaluate peak eosinophil counts (PEC). A higher number of eosinophils indicates more severe histological disease.	12 weeks
Secondary	Change from baseline in the Straumann Dysphagia Index (SDI) score	The SDI is a patient-reported outcome measure of dysphagia with a 7-day recall period. The SDI assesses the frequency and intensity of dysphagia on two separate 5-point and 6-point scales. Total SDI scores are calculated by adding the two sub-scores (range, 0-9), with a higher total score indicating more severe dysphagia.	2 weeks
Secondary	Change from baseline in the Straumann Dysphagia Index (SDI) score	The SDI is a patient-reported outcome measure of dysphagia with a 7-day recall period. The SDI assesses the frequency and intensity of dysphagia on two separate 5-point and 6-point scales. Total SDI scores are calculated by adding the two sub-scores (range, 0-9), with a higher total score indicating more severe dysphagia.	4 weeks
Secondary	Change from baseline in the Straumann Dysphagia Index (SDI) score	The SDI is a patient-reported outcome measure of dysphagia with a 7-day recall period. The SDI assesses the frequency and intensity of dysphagia on two separate 5-point and 6-point scales. Total SDI scores are calculated by adding the two sub-scores (range, 0-9), with a higher total score indicating more severe dysphagia.	8 weeks
Secondary	Change from baseline in the Straumann Dysphagia Index (SDI) score	The SDI is a patient-reported outcome measure of dysphagia with a 7-day recall period. The SDI assesses the frequency and intensity of dysphagia on two separate 5-point and 6-point scales. Total SDI scores are calculated by adding the two sub-scores (range, 0-9), with a higher total score indicating more severe dysphagia.	12 weeks
Secondary	Change from baseline in dysphagia measured on an 11 point Likert scale	The participant will assess the severity of their dysphagia symptoms (troubles to swallow) over the previous 7-days using an 11-point Likert scale where 0 = no trouble and 10 = most severe trouble swallowing.	4 weeks
Secondary	Change from baseline in dysphagia measured on an 11 point Likert scale	The participant will assess the severity of their dysphagia symptoms (troubles to swallow) over the previous 7-days using an 11-point Likert scale where 0 = no trouble and 10 = most severe trouble swallowing.	8 weeks
Secondary	Change from baseline in dysphagia measured on an 11 point Likert scale	The participant will assess the severity of their dysphagia symptoms (troubles to swallow) over the previous 7-days using an 11-point Likert scale where 0 = no trouble and 10 = most severe trouble swallowing.	12 weeks
Secondary	Change from baseline in odynophagia measured on an 11 point Likert scale	The participant will assess the severity of their pain during swallowing over the previous 7 days using an 11 point Likert scale where 0 = no pain and 10 = most severe pain during swallowing.	4 weeks
Secondary	Change from baseline in odynophagia measured on an 11 point Likert scale	The participant will assess the severity of their pain during swallowing over the previous 7 days using an 11 point Likert scale where 0 = no pain and 10 = most severe pain during swallowing.	8 weeks
Secondary	Change from baseline in odynophagia measured on an 11 point Likert scale	The participant will assess the severity of their pain during swallowing over the previous 7 days using an 11 point Likert scale where 0 = no pain and 10 = most severe pain during swallowing.	12 weeks
Secondary	Change from baseline in the EoE Endoscopic Reference Score (EREFS)	Endoscopic Reference Score (EREFS) scoring system is used to determine the severity of 5 endoscopic findings: edema, rings, exudates, furrows, and strictures. The total EREFS is calculated by summing the grades of the 5 individual endoscopic items (range, 0 to 9), with higher scores indicating more severe endoscopic disease.	4 weeks
Secondary	Change from baseline in the EoE Endoscopic Reference Score (EREFS)	Endoscopic Reference Score (EREFS) scoring system is used to determine the severity of 5 endoscopic findings: edema, rings, exudates, furrows, and strictures. The total EREFS is calculated by summing the grades of the 5 individual endoscopic items (range, 0 to 9), with higher scores indicating more severe endoscopic disease.	12 weeks
Secondary	Change from baseline in EoE Histology Scoring System (EoEHSS) score	The EoEHSS scores the stage and grade of 8 histologic items: eosinophil inflammation, basal zone hyperplasia, dilated intercellular spaces, eosinophil abscesses, surface layering, surface epithelial alteration, dyskeratotic epithelial cells and lamina propria fibrosis), on separate 4-point Likert scales. A composite EoEHSS grade and stage scores are calculated by summing the individual grade and stage items and dividing by the maximum score for evaluated items (range, 0-1). A lower score indicates improvement.	4 weeks
Secondary	Change from baseline in EoE Histology Scoring System (EoEHSS) score	The EoEHSS scores the stage and grade of 8 histologic items: eosinophil inflammation, basal zone hyperplasia, dilated intercellular spaces, eosinophil abscesses, surface layering, surface epithelial alteration, dyskeratotic epithelial cells and lamina propria fibrosis), on separate 4-point Likert scales. A composite EoEHSS grade and stage scores are calculated by summing the individual grade and stage items and dividing by the maximum score for evaluated items (range, 0-1). A lower score indicates improvement.	12 weeks