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NCT Number: NCT05608681

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

A Phase 1b/2 study to explore the safety, efficacy and pharmacokinetics of EP-104GI in adults with eosinophilic esophagitis (EoE). Endoscopic and histologic assessments will also be evaluated to understand the local effects of EP-104GI on eosinophilic EoE disease activity. Approximately 27 to 33 participants will be enrolled in dose escalation: 3-6 participants per dose cohort. 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). In the Phase 2 randomized dose optimization portion of the study, approximately 120 subjects will be randomized to Dose A (120 mg total dose), Dose B (160 mg total dose), or matching vehicle control, with an overall assignment ratio of 1:1:1. The total number of participants in both portions of the study will be approximately 160. The study involves 8-10 site visits spread over approximately 52 weeks. Participants in an extended PK sub study will have up to 4 additional visits, to a maximum of 108 weeks post-dose. The participants will either receive the active study drug (EP-104GI) or matching vehicle control. Matching vehicle control will be used only in randomized dose optimization portion of the study. Participants randomized to receive vehicle control may receive EP-104GI (Dose A or Dose B) following the completion of Week 24 providing they meet eligibility criteria for crossover to EP-104GI. Participants randomized to receive EP-104GI on Day 0 will not receive EP-104GI or vehicle control at Week 24. The study drug or matching vehicle control 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-104GI. Participants will complete questionnaires to assess symptoms of dysphagia and odynophagia and will undergo 3-5 EGDs with esophageal biopsies at the Baseline, Week 4 (dose escalation phase only), Week 12, Week 24 (randomized dose optimization phase only), Week 26, and Week 52 (randomized dose optimization phase only).

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Key information

Conditions

Eosinophilic Esophagitis Digestive System Diseases Eosinophilia Esophageal Diseases Esophagitis Gastroenteritis Gastrointestinal Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Leukocyte Disorders

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Campbelltown Private Hospital, Sydney, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Criteria for crossover to EP 104GI from vehicle control (randomized dose optimization portion):

  • Has completed the randomized dose optimization portion of the trial to Week 24, inclusive
  • Without safety concerns for receiving EP 104GI ie, does not meet exclusion criteria or have other safety issue

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, including carboxymethyl cellulose, and polysorbate 80, or to the ingredients in Synacthen / cosyntropin (used in the ACTH stimulation test);
  • 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.

Treatment and study plan

EP-104GI

Drug

Extended-release fluticasone propionate [FP] for injectable suspension for gastrointestinal administration, Powder suspended in vehicle

Matching vehicle control

Other

A sterile liquid containing sterile water and excipients necessary to prepare a uniform suspension of the powder.

Primary outcomes

  1. Dose Escalation- Incidence of treatment emergent adverse events (TEAEs)

    Time frame: 52 weeks

    TEAEs will be summarized by dose/cohort

  2. Dose Escalation- Severity of treatment emergent adverse events (TEAEs)

    Time frame: 52 weeks

    TEAEs will be summarized by dose/cohort and severity (mild, moderate, severe).

  3. Dose Escalation- Change from baseline in morning serum cortisol levels

    Time frame: 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.

  4. Dose Escalation- Plasma concentrations of fluticasone propionate

    Time frame: 108 weeks

    Plasma concentrations of fluticasone propionate over time will be used to calculate PK parameters for each dose/cohort.

  5. Dose Escalation- Change from baseline in physical examination results, BMI and weight change.

    Time frame: 12 weeks

    Physical examination results, BMI and weight will be summarized by dose/cohort and over time and compared to pre-dose values.

  6. Randomised Dose Optimization- Change from baseline in EoEHSS grade and stage scored in 3 regions of the esophagus within the injection area (proximal, mid, distal)

    Time frame: 24 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.

Secondary outcomes

  1. Dose Escalation- Peak eosinophil count (PEC)

    Time frame: 36 weeks

    Biopsy specimens will be used to evaluate peak eosinophil counts (PEC). A higher number of eosinophils indicates more severe histological disease.

  2. Dose Escalation- Change from baseline in the Straumann Dysphagia Index (SDI) score

    Time frame: 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.

  3. Dose Escalation- Change from baseline in dysphagia measured on an 11 point Likert scale

    Time frame: 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.

  4. Dose Escalation- Change from baseline in the EoE Endoscopic Reference Score (EREFS)

    Time frame: 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.

  5. Dose Escalation- Change from baseline in odynophagia measured on an 11 point Likert scale

    Time frame: 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.

  6. Dose Escalation- Change from baseline in EoE Histology Scoring System (EoEHSS) score

    Time frame: 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.

  7. Randomised Dose Optimization- Change from baseline in the Straumann Dysphagia Index (SDI) score

    Time frame: 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.

  8. Randomised Dose Optimization- Change from baseline in the Dysphagia symptom questionnaire (DSQ) v4.0 and "Dysphagia days"

    Time frame: 52 weeks

    The DSQ is assessed daily over a period of 14 days and comprises four questions; one question on whether the participant has eaten solid food and three questions on the presence and severity of EoE dysphagia."Dysphagia Days" is defined as the number of days with a yes answer to the following question: During any meal today, did food go down slowly or get stuck in your throat or chest?

  9. Randomised Dose Optimization- Change from baseline in the Eosinophilic Esophagitis Impact Questionnaire (EoE IQ)

    Time frame: 52 weeks

    The EoE-IQ is a validated PRO instrument consisting of 11 questions assessing the impact of EoE on health related quality of life.

  10. Randomised Dose Optimization- Change from baseline in the Patient Global Impression of Change (PGIC)

    Time frame: 52 weeks

    The PGIC reflects a participant's belief about the efficacy of treatment on a 7 point scale rating on a 4 point scale.

  11. Randomised Dose Optimization- Change from baseline in the Patient Global Impression of Severity (PGIS)

    Time frame: 52 weeks

    The PGIS reflects a participant's belief about the efficacy of treatment based on severity ranging from none to very severe.

  12. Randomised Dose Optimization- Change from baseline in peak eosinophil count (PEC)

    Time frame: 52 weeks

    Biopsy specimens will be used to evaluate peak eosinophil counts (PEC). A higher number of eosinophils indicates more severe histological disease.

  13. Randomised Dose Optimization- Change from baseline in the EoE Endoscopic Reference Score (EREFS) in 3 regions of the esophagus within the injection area (proximal, mid, distal)

    Time frame: 52 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.

  14. Randomised Dose Optimization- Change in endoscopist's global impression of severity

    Time frame: 52 weeks

    The PGIC reflects a participant's belief about the efficacy of treatment on a 7 point scale rating overall improvement; the PGIS reflects a participant's belief about the severity of their symptoms on a 4 point scale

  15. Randomised Dose Optimization- Change from baseline in EoE Histology Scoring System (EoEHSS) score in 3 regions of the esophagus within the injection area (proximal, mid, distal), excluding Week 24 as this is the primary endpoint

    Time frame: 52 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.

  16. Randomised Dose Optimization- Change from baseline in morning serum cortisol levels

    Time frame: 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.

  17. Randomised Dose Optimization- Change from baseline in vital signs (temperature, blood pressure, pulse, and respiratory rate) results

    Time frame: 52 weeks

    Vital signs (temperature, blood pressure, pulse, and respiratory rate) results will be summarized by dose/cohort and over time and compared to pre-dose values.

  18. Randomised Dose Optimization- Change from baseline in physical examination results, BMI and weight change.

    Time frame: 52 weeks

    Physical examination results, BMI and weight will be summarized by dose/cohort and over time and compared to pre-dose values.

  19. Randomised Dose Optimization- Plasma concentrations of fluticasone propionate

    Time frame: 108 weeks

    Plasma concentrations of fluticasone propionate over time will be used to calculate PK parameters for each dose/cohort.

Study contacts

Contact information is provided by the study sponsor or research team.

Pranali Ravikumar, MS

CONTACT

[email protected]

647-895-3016

Sponsors and collaborators

Lead sponsor

Eupraxia Pharmaceuticals Inc.

Industry

Registry information

Official study title

A Phase 1b/2 Trial Evaluating the Safety, Pharmacokinetics, and Efficacy of EP-104GI in Adults With Eosinophilic Esophagitis (RESOLVE)

Acronym: RESOLVE

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Nov 8, 2022
Registry last updated
Mar 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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