Clinical trial NCT05608681: A Trial to Evaluate EP-104IAR in Adults With Eosinophilic Esophagitis (EoE).
Official title: A Phase 1b/2a, Open Label Trial Evaluating the Safety, Pharmacokinetics, and Efficacy of EP-104IAR in Adults With Eosinophilic Esophagitis (RESOLVE)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Eosinophilic Esophagitis
Lead sponsor: Eupraxia Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-08
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment emergent adverse events (TEAEs)
timeFrame: 52 weeks
measure: Severity of treatment emergent adverse events (TEAEs)
timeFrame: 52 weeks
measure: Change from baseline in morning serum cortisol levels
timeFrame: 52 weeks
measure: Plasma concentrations of fluticasone propionate
timeFrame: 52 weeks
measure: Change from baseline in clinical safety laboratory measurements
timeFrame: 12 weeks
measure: Change from baseline in vital signs and physical examination results
timeFrame: 12 weeks
Secondary outcomes:
measure: Peak eosinophil count (PEC)
timeFrame: 4 weeks
measure: Peak eosinophil count (PEC)
timeFrame: 12 weeks
measure: Peak eosinophil count (PEC)
timeFrame: 36 weeks
measure: Change from baseline in the Straumann Dysphagia Index (SDI) score
timeFrame: 2 weeks
measure: Change from baseline in the Straumann Dysphagia Index (SDI) score
timeFrame: 4 weeks
measure: Change from baseline in the Straumann Dysphagia Index (SDI) score
timeFrame: 8 weeks
measure: Change from baseline in the Straumann Dysphagia Index (SDI) score
timeFrame: 12 weeks
measure: Change from baseline in the Straumann Dysphagia Index (SDI) score
timeFrame: 24 weeks
measure: Change from baseline in the Straumann Dysphagia Index (SDI) score
timeFrame: 36 weeks
measure: Change from baseline in the Straumann Dysphagia Index (SDI) score
timeFrame: 52 weeks
measure: Change from baseline in dysphagia measured on an 11 point Likert scale
timeFrame: 4 weeks
measure: Change from baseline in dysphagia measured on an 11 point Likert scale
timeFrame: 8 weeks
measure: Change from baseline in dysphagia measured on an 11 point Likert scale
timeFrame: 12 weeks
measure: Change from baseline in dysphagia measured on an 11 point Likert scale
timeFrame: 24 weeks
measure: Change from baseline in dysphagia measured on an 11 point Likert scale
timeFrame: 36 weeks
measure: Change from baseline in dysphagia measured on an 11 point Likert scale
timeFrame: 52 weeks
measure: Change from baseline in odynophagia measured on an 11 point Likert scale
timeFrame: 4 weeks
measure: Change from baseline in odynophagia measured on an 11 point Likert scale
timeFrame: 8 weeks
measure: Change from baseline in odynophagia measured on an 11 point Likert scale
timeFrame: 12 weeks
measure: Change from baseline in odynophagia measured on an 11 point Likert scale
timeFrame: 24 weeks
measure: Change from baseline in odynophagia measured on an 11 point Likert scale
timeFrame: 36 weeks
measure: Change from baseline in odynophagia measured on an 11 point Likert scale
timeFrame: 52 weeks
measure: Change from baseline in the EoE Endoscopic Reference Score (EREFS)
timeFrame: 4 weeks
measure: Change from baseline in the EoE Endoscopic Reference Score (EREFS)
timeFrame: 12 weeks
measure: Change from baseline in the EoE Endoscopic Reference Score (EREFS)
timeFrame: 36 weeks
measure: Change from baseline in EoE Histology Scoring System (EoEHSS) score
timeFrame: 4 weeks
measure: Change from baseline in EoE Histology Scoring System (EoEHSS) score
timeFrame: 12 weeks
measure: Change from baseline in EoE Histology Scoring System (EoEHSS) score
timeFrame: 36 weeks
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Vancouver
country: Canada
facility: G.I. Research Institute
state: British Columbia
city: Montréal
country: Canada
facility: McGill University Health Center
state: Quebec
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
Study officials:
affiliation: Eupraxia Pharmaceuticals
name: Amanda Malone, PhD
role: STUDY_DIRECTOR
References: