A Trial to Evaluate EP-104IAR in Adults With Eosinophilic Esophagitis (EoE).
- Registration Number
- NCT05608681
- Lead Sponsor
- Eupraxia Pharmaceuticals Inc.
- Brief 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.
Approximately 27 to 33 participants will be enrolled in dose escalation: 3-6 participants per dose cohort in approximately 9 cohorts. The number of participants enrolled in escalation will depend on the number of dose escalation cohorts evaluated, and dose cohorts needing to be expanded.
An additional 10-24 participants will be enrolled in 1 or 2 cohorts of 10-12 participants each at tolerable dose regimen(s) selected based on the accumulated clinical data to identify the recommended phase 2 dose(s) (RP2D).
The study involves 8-10 site visits spread over approximately 24-52 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 3-4 EGDs with esophageal biopsies at the Baseline/Dosing Visit, at 4, 12 and 36 weeks post dose.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 57
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description EP-104IAR 30 mg EP-104IAR 12 submucosal injections of EP-104IAR administered during an EGD procedure at the Baseline/Dosing visit. EP-104IAR 48 mg EP-104IAR 12 submucosal injections of EP-104IAR administered during an EGD procedure at the Baseline/Dosing visit. EP-104IAR 120 mg EP-104IAR 20 submucosal injections of EP-104IAR administered during an EGD procedure at the Baseline/Dosing visit. EP-104IAR 64 mg EP-104IAR 16 submucosal injections of EP-104IAR administered during an EGD procedure at the Baseline/Dosing visit. EP-104IAR 96 mg EP-104IAR 16 submucosal injections of EP-104IAR administered during an EGD procedure at the Baseline/Dosing visit. EP-104IAR 4 mg EP-104IAR 4 submucosal injections of EP-104IAR administered during an EGD procedure at the Baseline/Dosing visit. EP-104IAR 20 mg EP-104IAR 8 submucosal injections of EP-104IAR administered during an EGD procedure at the Baseline/Dosing visit. EP-104IAR 72 mg EP-104IAR 12 submucosal injections of EP-104IAR administered during an EGD procedure at the Baseline/Dosing visit. EP-104IAR 8 mg EP-104IAR 8 submucosal injections of EP-104IAR administered during an EGD procedure at the Baseline/Dosing visit.
- Primary Outcome Measures
Name Time Method Change from baseline in clinical safety laboratory measurements 12 weeks Clinical safety laboratory measurements will be summarized by dose/cohort and over time and compared to pre-dose values.
Incidence of treatment emergent adverse events (TEAEs) 52 weeks TEAEs will be summarized by dose/cohort
Severity of treatment emergent adverse events (TEAEs) 52 weeks TEAEs will be summarized by dose/cohort and severity (mild, moderate, severe).
Change from baseline in morning serum cortisol levels 52 weeks 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.
Plasma concentrations of fluticasone propionate 52 weeks Plasma concentrations of fluticasone propionate over time will be used to calculate PK parameters for each dose/cohort.
Change from baseline in vital signs and physical examination results 12 weeks Vital signs and physical examination results will be summarized by dose/cohort and over time and compared to pre-dose values.
- Secondary Outcome Measures
Name Time Method Peak eosinophil count (PEC) 36 weeks Biopsy specimens will be used to evaluate peak eosinophil counts (PEC). A higher number of eosinophils indicates more severe histological disease.
Change from baseline in the Straumann Dysphagia Index (SDI) score 52 weeks 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.
Change from baseline in dysphagia measured on an 11 point Likert scale 52 weeks 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.
Change from baseline in EoE Histology Scoring System (EoEHSS) score 36 weeks 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.
Change from baseline in odynophagia measured on an 11 point Likert scale 52 weeks 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.
Change from baseline in the EoE Endoscopic Reference Score (EREFS) 36 weeks 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.
Trial Locations
- Locations (5)
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
McGill University Health Center
🇨🇦Montréal, Quebec, Canada
Amsterdam UMC
🇳🇱Amsterdam, Netherlands
G.I. Research Institute
🇨🇦Vancouver, British Columbia, Canada