A Trial to Evaluate EP 104GI in Adults with Eosinophilic Esophagitis (EoE) (RESOLVE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Eupraxia Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06], Diseases [C] - Immune System Diseases [C20]

Trial duration

6 Feb 2023 → ongoing

Decision date (initial)

2024-09-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Eupraxia Pharmaceuticals Inc.

External identifiers

EU CT number

2024-516689-13-00

EudraCT number

2022-001992-15

WHO UTN

U1111-1307-9108

ClinicalTrials.gov

NCT05608681

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

Phase 1b: To determine the safety, tolerability, and RP2D(s) and regimen(s) of EP 104GI
Phase 1b: To determine the pharmacokinetic (PK) profile of EP 104GI
Phase 2: To evaluate the efficacy of EP 104GI on the severity and extent of Eosinophilic Esophagitis (EoE) disease measured by the EoE Histology Scoring System (EoEHSS)

Secondary objectives 6

1. Phase 1b: To evaluate the efficacy of EP 104GI on eosinophilic esophagitis (EoE) disease activity as measured by symptoms, endoscopy, and histology
2. Phase 2: To evaluate the efficacy of EP 104GI on EoE disease activity as measured by symptoms measured by patient reported outcomes (PROs) including the Dysphagia Symptom Questionnaire v4.0 (DSQ)
3. Phase 2: To evaluate the efficacy of EP 104GI on EoE disease activity as measured by endoscopy and histology
4. Phase 2: To determine the safety and tolerability of the selected dose(s) and regimen(s) of EP 104GI
5. Phase 2: To determine the PK profile of the selected dose(s) and regimen(s) EP 104GI
6. Phase 2: To evaluate exploratory markers of efficacy

Conditions and MedDRA coding

Eosinophilic esophagitis

Study design 5 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Adults 18 to 75 years of age, inclusive
2. 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
3. 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)
4. Willing and able to adhere to study-related procedures and visit schedule
5. Willing and able to provide informed consent
6. 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)
7. 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 23

1. 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
2. Presence of oral or esophageal mucosal infection of any type (bacterial, viral, or fungal)
3. Any oropharyngeal or dental condition that prevents normal eating
4. Known severe esophageal motility disorders other than EoE
5. 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
6. 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.
7. 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
8. 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)
9. 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
10. 10. Use 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)
11. 11. Initiation of an elimination diet or elemental diet within 30 days prior to dosing (dietary therapy must remain stable throughout the study)
12. Use of biologic immunomodulators in the 90 days prior to dosing
13. Use of immunosuppressive drugs, or potent cytochrome P450 3A4 inhibitors in the 90 days prior to dosing
14. 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
15. Morning serum cortisol level ≤ 5 μg/dL (138 nmol/L) at Screening visit
16. 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
17. Previous participation in this study and had received study treatment
18. Female participants who are pregnant, breastfeeding, or planning to become pregnant within 52 weeks postdose
19. 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. Elevated 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)
20. 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
21. History of patient reported alcohol or drug abuse within 6 months prior to screening
22. Unwillingness to withhold protocol prohibited medications during the trial
23. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Frequency and severity of treatment-emergent adverse events (TEAEs)
2. Change from baseline in clinical safety laboratory measurements
3. Change from baseline in morning serum cortisol levels on Day 1 postdose and timepoints up to 52 Weeks postdose
4. Change from baseline in vital signs at 1 and 24 hours postdose and timepoints up to 52 Weeks postdose.
5. 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)

Secondary endpoints 9

1. Change from baseline in EoE Histology Scoring System (EoEHSS) grade and stage scores at timepoints up to 52 Weeks postdose
2. 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
3. Change from baseline in the EoE Endoscopic Reference Score (EREFS) at timepoints up to 52 Weeks postdose
4. Change from baseline in the Straumann Dysphagia Index (SDI) patient reported outcome (PRO) score at timepoints up to 52 Weeks postdose
5. 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)
6. 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)
7. Change from baseline in dysphagia measured on an 11 point Likert scale at timepoints up to 52 Weeks postdose
8. Change from baseline in odynophagia measured on an 11 point Likert scale at timepoints up to 52 Weeks postdose
9. 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)

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eupraxia Pharmaceuticals Inc.

Sponsor organisation

Eupraxia Pharmaceuticals Inc.

Address

2198 Yukon Street

City

Vancouver

Postcode

V5Y 3P1

Country

Canada

Scientific contact point

Organisation

Eupraxia Pharmaceuticals Inc.

Contact name

Susan Oakley

Public contact point

Organisation

Eupraxia Pharmaceuticals Inc.

Contact name

Susan Oakley

Third parties 6

Locations

1 EU/EEA country · 2 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 21 files

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

Application history

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