FLUTICASONE PROPIONATE for Eosinophilic esophagitis

Inclusion criteria

• {"criterion_text":"- Adults 18 to 75 years of age, inclusive\n- Symptomatic EoE defined as: a. Phase 1b, dose escalation portion: SDI score ≥ 5 at screening and baseline; Phase 2, randomized portion: SDI score ≥ 5 at screening and DSQ total score ≥ 10 over a 14 day period during screening (at least 11 of 14 days must be completed) b. Confirmed historical diagnosis of EoE with PEC > 15/hpf\n- For women of childbearing potential, a negative pregnancy test (at baseline) and willing to use a highly effective method of birth control for at least 4 weeks before Day 0, and for at least 52 weeks following the dose of study drug (Day 0 or Week 24)\n- Willing and able to adhere to study-related procedures and visit schedule\n- Willing and able to provide informed consent\n- Criteria for crossover to EP 104GI from vehicle control (Phase 2, randomized dose optimization portion): 1. Has completed the Phase 2, randomized dose optimization portion of the trial to Week 24, inclusive 2. Without safety concerns for receiving EP 104GI (i.e., does not meet exclusion criteria or have other safety issue)\n- Criteria for participation in the Extended PK Substudy: 1. Willing and able to provide informed consent for the Extended PK Substudy. 2. Has not used any products containing FP within 7 days prior to the PK visit. 3. Had detectable plasma FP (above the lower limit of quantitation) at their previous PK visit."}

Exclusion criteria

• {"criterion_text":"- Any concomitant esophageal disease and relevant GI disease including but not limited to eosinophilic gastritis or enteritis (defined by clinicopathologic features), erosive esophagitis Los Angeles grade C or higher, Barrett’s esophagus, previous esophageal surgery, Celiac disease, inflammatory bowel disease, or any condition or history of illness or laboratory abnormality that in the investigator’s judgment might interfere with study procedures or ability to complete the study. Note: Participants with occasional gastroesophageal reflux disease (GERD) symptoms without severe (Los Angeles grade C or higher) endoscopic erosive reflux esophagitis are permitted\n- 10.\tUse of a new inhaled or intranasal corticosteroid within 60 days prior to dosing, or a change in dose of an inhaled or intranasal corticosteroid within 60 days of dosing (a temporary dose change lasting ≤ 14 days is permitted)\n- 11.\tInitiation of an elimination diet or elemental diet within 30 days prior to dosing (dietary therapy must remain stable throughout the study)\n- Use of biologic immunomodulators in the 90 days prior to dosing\n- Use of immunosuppressive drugs, or potent cytochrome P450 3A4 inhibitors in the 90 days prior to dosing\n- Initiated, discontinued, or changed dosage regimen of PPIs for any condition such as GERD or allergic rhinitis within 4 weeks prior to dosing. Doses must remain stable throughout the study\n- Morning serum cortisol level ≤ 5 μg/dL (138 nmol/L) at Screening visit\n- Use of another investigational product within the 30 days prior to dosing, or an investigational biologic within 90 days prior to dosing, or current/planned participation in another interventional trial during this study\n- Previous participation in this study and had received study treatment\n- Female participants who are pregnant, breastfeeding, or planning to become pregnant within 52 weeks postdose\n- The following laboratory values at screening: a. Elevated alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 3× upper limit of normal (ULN), bilirubin, alkaline phosphatase (ALP), and/or creatinine > 1.5× ULN b.\tElevated prothrombin time or international normalized ratio > 1.5× ULN c. Hemoglobin A1c (HbA1c) value of ≥ 8.0% (64 mmol/mol) (Note: individuals with insulin dependence or non insulin dependent poorly controlled diabetes will be excluded)\n- Presence of oral or esophageal mucosal infection of any type (bacterial, viral, or fungal)\n- Malignancies or history of malignancy within 5 years of screening, except for adequately treated or completely excised nonmetastatic basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ\n- History of patient reported alcohol or drug abuse within 6 months prior to screening\n- Unwillingness to withhold protocol prohibited medications during the trial\n- Any other reason, including a severe acute or chronic medical or psychiatric condition(s) or laboratory abnormality, that, in the opinion of the investigator, is likely to unfavorably alter participant risk benefit, confound study results, or make it difficult for the participant to fully comply with study requirements\n- Any oropharyngeal or dental condition that prevents normal eating\n- Known severe esophageal motility disorders other than EoE\n- Contraindication to or factors that substantially increase the risk associated with EGD or esophageal biopsy, or narrowing of the esophagus that precludes EGD with a standard 9 10 mm endoscope, stricture requiring dilation within the 8 weeks prior to Screening, or the need for dilation prior to EGD at baseline\n- A history or presence of any condition for which the use of corticosteroids is contraindicated (e.g., insulin dependent diabetes mellitus, Cushing’s syndrome, Addison’s disease, cortisol related endocrinopathy, etc.) Note: Participants with well controlled non insulin dependent diabetes are permitted.\n- Known active or quiescent systemic fungal, bacterial (including tuberculosis), viral (including human immunodeficiency virus [HIV], hepatitis B virus [HBV], or hepatitis C virus [HCV]), or parasitic infections, or ocular herpes simplex. Or any infection requiring intravenous [IV] antibiotics within 4 weeks of baseline, or oral antibiotics within 2 weeks of baseline\n- Known hypersensitivity, or intolerance to corticosteroids, or to any of the ingredients in the investigational medicinal product (IMP), including carboxymethyl cellulose, and polysorbate 80, or to the ingredients in Synacthen / cosyntropin (used in the ACTH stimulation test)\n- Use of systemic corticosteroids and any use of FP within 60 days prior to dosing, or swallowed topical corticosteroids within 60 days prior to dosing, or extended use of high potency dermal topical corticosteroids within 60 days prior to dosing"}

Primary endpoints

• {"endpoint_text":"- Frequency and severity of treatment-emergent adverse events (TEAEs)","definition_or_measurement_approach":"Collection and assessment of treatment-emergent adverse events (TEAEs) recorded as frequency and severity during study follow-up."}
• {"endpoint_text":"- Change from baseline in clinical safety laboratory measurements","definition_or_measurement_approach":"Change from baseline in clinical safety laboratory measurements (as captured at scheduled safety lab timepoints)."}
• {"endpoint_text":"- Change from baseline in morning serum cortisol levels on Day 1 postdose and timepoints up to 52 Weeks postdose","definition_or_measurement_approach":"Morning serum cortisol measured at Day 1 postdose and at scheduled timepoints up to 52 weeks postdose; endpoint is change from baseline."}
• {"endpoint_text":"- Change from baseline in vital signs at 1 and 24 hours postdose and timepoints up to 52 Weeks postdose.","definition_or_measurement_approach":"Vital signs measured at 1 and 24 hours postdose and at scheduled timepoints up to 52 weeks postdose; endpoint is change from baseline."}
• {"endpoint_text":"- Plasma concentrations of FP, measured at baseline (predose), 2 and 24 hours postdose, and timepoints up to 108 Weeks postdose (dependent on the portion of the study participated in)","definition_or_measurement_approach":"Plasma fluticasone propionate (FP) concentrations measured at predose, 2 and 24 hours postdose and at additional scheduled timepoints up to 108 weeks postdose (depending on study portion)."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline in EoE Histology Scoring System (EoEHSS) grade and stage scores at timepoints up to 52 Weeks postdose","definition_or_measurement_approach":"EoEHSS grade and stage scores compared to baseline at scheduled timepoints up to 52 weeks postdose."}
• {"endpoint_text":"- Histological response mapped over the surface of the esophagus as a function of proximity to, and size of dose, measured by peak eosinophil count (PEC) at timepoints up to 52 Weeks postdose","definition_or_measurement_approach":"Peak eosinophil count (PEC) measured on esophageal biopsies at scheduled timepoints up to 52 weeks postdose; response mapped by location/proximity and dose size."}
• {"endpoint_text":"- Change from baseline in the EoE Endoscopic Reference Score (EREFS) at timepoints up to 52 Weeks postdose","definition_or_measurement_approach":"EREFS change from baseline at scheduled timepoints up to 52 weeks postdose."}
• {"endpoint_text":"- Change from baseline in the Straumann Dysphagia Index (SDI) patient reported outcome (PRO) score at timepoints up to 52 Weeks postdose","definition_or_measurement_approach":"SDI PRO score change from baseline at scheduled timepoints up to 52 weeks postdose."}
• {"endpoint_text":"- Change from baseline in the Dysphagia symptom questionnaire (DSQ) v4.0 and \"Dysphagia days\" at timepoints up to 52 Weeks postdose (Phase 2; randomized portion of the study only)","definition_or_measurement_approach":"DSQ v4.0 scores and Dysphagia days change from baseline at scheduled timepoints up to 52 weeks postdose (Phase 2 randomized portion only)."}
• {"endpoint_text":"- Change from baseline in Patient Global Impression of Change and Patient Global Impression of Severity (PGIC/PGIS) at timepoints up to 52 Weeks postdose (Phase 2; randomized portion of the study only)","definition_or_measurement_approach":"PGIC and PGIS change from baseline at scheduled timepoints up to 52 weeks postdose (Phase 2 randomized portion only)."}
• {"endpoint_text":"- Change from baseline in dysphagia measured on an 11 point Likert scale at timepoints up to 52 Weeks postdose","definition_or_measurement_approach":"11-point Likert scale for dysphagia assessed and compared to baseline at scheduled timepoints up to 52 weeks postdose."}
• {"endpoint_text":"- Change from baseline in odynophagia measured on an 11 point Likert scale at timepoints up to 52 Weeks postdose","definition_or_measurement_approach":"11-point Likert scale for odynophagia assessed and compared to baseline at scheduled timepoints up to 52 weeks postdose."}
• {"endpoint_text":"- Change from baseline in the Eosinophilic Esophagitis Impact Questionnaire (EOE-IQ) at timepoints up to 52 Weeks postdose (Phase 2; randomized portion of the study only)","definition_or_measurement_approach":"EOE-IQ change from baseline at scheduled timepoints up to 52 weeks postdose (Phase 2 randomized portion only)."}

Netherlands

Earliest CTIS Part Ii Submission Date

09-09-2024

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

511

Number Of Sites

2

Number Of Participants

5

Primary sponsor

Full Name

Eupraxia Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Canada

Contract research organisations

Name

Charles River Laboratories Montreal ULC

Responsibilities

sponsorDuties codes: 4

Name

Acelabio (US) Inc.

Responsibilities

sponsorDuties codes: 4

Name

Cerba Research

Responsibilities

sponsorDuties codes: 4

Name

Syneos Health Clinique Inc.

Responsibilities

sponsorDuties codes: 4

Third parties

• {"country":"Canada","full_name":"Charles River Laboratories Montreal ULC","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Acelabio (US) Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Clinigen Clinical Supplies Management GmbH","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Syneos Health Clinique Inc.","duties_or_roles":"4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Canada","full_name":"Alimentiv Inc.","duties_or_roles":"1,10,12,2,3,5,6,7,8","organisation_type":"Pharmaceutical company"}