A Study to Assess the Efficacy, Safety and Tolerability of IRL201104 in Adults With Active Eosinophilic Esophagitis

Study Overview
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Brief Summary
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The purpose of this study is to asses the efficacy, safety and tolerability of repeat doses of IRL201104 in Adult Participants with Active Eosinophilic Esophagitis (EoE)

Official Title
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A Phase 2a, Double-blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy, Safety, and Tolerability of IRL201104 in Adult Participants With Active Eosinophilic Esophagitis (EoE)

Conditions
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Eosinophilic Esophagitis

Intervention / Treatment
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* Drug: IRL201104
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 75 years old, inclusive, at the time of signing the informed consent form. Documented diagnosis of EoE by endoscopy prior to screening. Note: Must include a demonstration of intraepithelial eosinophilic infiltration (peak cell count ≥ 15 eos/hpf [400×]) from esophageal biopsy specimens from endoscopy. History (by participant report) of on average at least 2 episodes of dysphagia (with intake of solids off anti-inflammatory therapy) per week in the 4 weeks prior to screening, and on average at least 2 episodes of documented dysphagia per week during any 2 consecutive weeks (qualifying period) between screening and baseline; dysphagia is defined as trouble swallowing solid food, or having solid food stick, by participant report; and completed the DSQ on ≥ 70% of days during the qualifying period prior to baseline (Visit 1). Must remain on a stabilized diet for at least 6 weeks prior to screening and during the course of the study; stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups. Must be willing and able to continue any dietary therapy and/or medical regimens (including gastric acid suppression) in effect at the screening visit. There should be no change to these regimens during the study participation. Willing and able to comply with all clinic visits and study-related procedures. Able to understand and complete study-related questionnaires. Provide signed informed consent. Esophagogastroduodenoscopy (EGD) with photographs performed at screening (qualifying EGD), with a demonstration of intraepithelial eosinophilic infiltration (peak cell count ≥15 eos/hpf) in at least 2 of the 3 biopsied esophageal regions (proximal, mid, or distal). Exclusion Criteria: Prior participation in an IRL201104 clinical study. Has any current disease of the gastrointestinal tract (aside from EoE) that may impact, in the investigator's opinion, the patient's EoE disease status. This includes, but not limited to: eosinophilic gastritis, eosinophilic enteritis, eosinophilic duodenitis, eosinophilic colitis, or proctitis; inflammatory bowel disease; or celiac disease. Has other causes of esophageal eosinophilia or the following diseases: hypereosinophilic syndromes, Churg-Strauss vasculitis (eosinophilic granulomatosis with polyangiitis), or peripheral blood absolute eosinophil count of > 1500 eosinophils/μL. Has presence of oral or esophageal mucosal infection of any type. Has any condition affecting the esophageal mucosa or altering esophageal motility other than EoE. History of achalasia, active Helicobacter pylori infection, Crohn's disease, ulcerative colitis, celiac disease, and prior esophageal surgery (with the exception of a surgical repair of an EoE complication). Any esophageal stricture unable to be passed with a standard, diagnostic, adult (9 to 10 mm) upper endoscope or any critical esophageal stricture that requires dilation at screening; or dilation within 2 months prior to screening. On a pure liquid diet or any mouth or dental condition that prevents normal eating. Has initiated, discontinued, or changed dosage regimen of PPIs within the 4 weeks prior to the qualifying EGD, between the qualifying EGD and baseline visit (Visit 1), or anticipates changes in the use of PPI during the study. PPI must remain constant throughout the study. History of bleeding disorders or esophageal varices. Use of anticoagulants within 2 weeks prior to screening. Participants should not stop these agents solely to become eligible for entry into this study. Treatment with an investigational drug within 2 months or within 5 half-lives (if known), whichever is longer, prior to screening. Use of systemic corticosteroids within 3 months or swallowed topical corticosteroids within 6 weeks prior to screening. Treatment with oral immunotherapy (OIT) within 6 months prior to screening. Allergen immunotherapy (sublingual immunotherapy [SLIT] and/or subcutaneous immunotherapy [SCIT]), unless on a stable dose for at least 1 year prior to screening. The following treatments within 3 months before the screening visit, or any condition that, in the opinion of the investigator, is likely to require such treatment(s) during the study: Systemic immunosuppressive/immunomodulating drugs (eg, omalizumab, cyclosporine, mycophenolate-mofetil, interferon [IFN]γ, Janus kinase inhibitors, azathioprine, methotrexate, and other biologics that are ongoing [eg, dupilumab, benralizumab, mepolizumab, or vedolizumab]). Diagnosed with active parasitic infection; or suspected parasitic infection, unless clinical and (if necessary) laboratory assessments have ruled out active infection before randomization. Chronic or acute infection requiring treatment with systemic antibiotics, antivirals, or antifungals within 1 month prior to screening. Use of oral antibiotics/anti-infectives within 2 weeks prior to screening. Known or suspected immunosuppression, including history of invasive opportunistic infections (eg, tuberculosis, non-tuberculous mycobacterial infections, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution, or otherwise recurrent infections of abnormal frequency, or prolonged infections suggesting an immunocompromised status, as judged by the investigator. Known history of human immunodeficiency virus (HIV) infection. Positive or indeterminate hepatitis B surface antigen (HBsAg) or hepatitis C antibody at screening. Moderate or severe renal impairment (eGFR <60 mL/min/1.73 m2) or end stage renal disease. Elevated transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) > 3 times the upper limit of normal (ULN) at screening. History of malignancy within 5 years prior to screening, except completely treated in situ carcinoma of the cervix and completely treated and resolved nonmetastatic squamous or basal cell carcinoma of the skin. Any other medical or psychological condition including relevant laboratory abnormalities at screening that, in the opinion of the investigator, suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the participant as a result of his/her participation in this clinical study, may make the participant's participation unreliable, or may interfere with study assessments. The specific justification for participants excluded under this criterion will be noted in study documents (eg, chart notes, electronic case report form). These may include participant-reported alcohol or drug abuse and severe concomitant illness(es). Planned or anticipated use of any prohibited medications and procedures (as described in the exclusion criteria) during study treatment. Treatment with a live (attenuated) vaccine within 3 months prior to screening and/or treatment of a killed vaccine within 30 days prior to screening, until the end of the study with the exception of a coronavirus disease of 2019 (COVID-19) vaccine, as described in Section 9.2.1. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study. Women unwilling to use adequate birth control, if of reproductive potential* and sexually active. Adequate birth control is defined as agreement to consistently practice an effective and accepted method of contraception throughout the duration of the study and for 30 days after the last dose of study treatment. These include: hormonal contraceptives, intrauterine device, or double barrier contraception (ie, condom and diaphragm), or male partner with documented vasectomy. For females, menopause is defined as at least 12 consecutive months without menses; to include laboratory confirmation of post-menopausal status (ie, a follicle stimulating hormone (FSH) of 2.25 U/mL must be documented). Hysterectomy, bilateral oophorectomy, or bilateral tubal ligation must be documented, as applicable; if documented, women with these conditions are not required to use additional contraception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: IRL201104 Dose A<br>IRL201104 IV on Days 0, 7, and 14 | Drug: IRL201104<br>* lyophilised powder for reconstitution for IV dosing<br>|
| Experimental: Arm 2: IRL201104 Dose B<br>IRL201104 IV on Days 0, 7, and 14 | Drug: IRL201104<br>* lyophilised powder for reconstitution for IV dosing<br>|
| Placebo Comparator: Arm 3: Placebo<br>Placebo IV on Days 0, 7, and 14 | Drug: Placebo<br>* Matching placebo for IRL201104<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the peak esophageal intraepithelial eosinophil count at Week 4. | The change from baseline in histologic eosinophil count in each treatment group will be summarized as the mean, standard deviation, median, minimum, and maximum | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in Dysphagia Symptom Questionnaire (DSQ) score from baseline. The DSQ is used to measure the frequency and intensity of dysphagia. The DSQ scores can range from 0 to 84, with a lower score indicating less frequent or less severe dysphagia | The change from baseline in DSQ score in each treatment group will be summarized as the mean, standard deviation, median, minimum, and maximum | 8 weeks | 
| Proportion of participants achieving peak esophageal intraepithelial eosinophil count of < 15 eos/hpf | Number and the proportion of participants with a histologic eosinophil count of < 15 eos/hpf will be summarized for each treatment group | 4 weeks | 
| Treatment Emergent Adverse Events | All TEAEs will be summarized overall and for each body system and preferred term by treatment group, relationship to investigational product, and severity | 8 weeks | 
| Vital Signs: Blood pressure | Summary statistics, by and across randomized treatment group | 8 weeks | 
| Vital Signs: Pulse rate | summarized by treatment group at baseline and at each scheduled visit | 8 weeks | 
| Vital Signs: Oral body Temperature | summarized by treatment group at baseline and at each scheduled visit | 8 weeks | 
| Vital Signs: Respiration rate | summarized by treatment group at baseline and at each scheduled visit | 8 weeks | 
| Safety Laboratory Data: Biochemistry | Glucose, liver function tests, urea, and electrolytes will be analysed by summary statistics, by and across randomized treatment group at baseline and at subsequent scheduled visits. | 8 weeks | 
| Safety Laboratory Data: Haematology | Full blood count variables will be analysed by summary statistics, by and across randomized treatment group at baseline and at subsequent scheduled visits. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EoE