First-in-Human Single and Multiple Dose of EB8018

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety profile of single and multiple doses of EB8018 in healthy male subjects, to determine the pharmacokinetic profile of single and multiple doses of EB8018 in healthy male subjects and to assess preliminary effects of EB8018 on the healthy male gut microbiome.

Detailed Description
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Crohn's Disease is a chronic inflammatory disease of the gastrointestinal tract. Emerging evidence suggests that the microbiome plays an important role in triggering an abnormal mucosal immune response in patients with Crohn's Disease. Independent studies have demonstrated an imbalance of the microbiome with a significant increase of E coli with invasive properties, termed adherent-invasive E coli (AIEC). These AIEC bacteria attach to the gut wall of susceptible patients via the fimbrial adhesion protein FimH, and subsequently trigger inflammation by invading and proliferating within the gut wall. EB8018 is an oral small molecule that is designed to block FimH thereby preventing the entry of AIEC into the gut wall thereby disarming the bacteria without disrupting the gut microbiome.

Official Title
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A Randomised, Double-Blind, Placebo-Controlled Study of a Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) of a FimH Antagonist, EB8018, in Healthy Volunteers.

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Single Ascending Doses of EB8018
* Drug: Single Ascending Doses of placebo
* Drug: Multiple Ascending Doses of EB8018
* Drug: Multiple Ascending Doses of placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males Age ≥ 18 to ≤ 55 years of age Body mass index of 19.0 to 30.0 kg/m2 Normal ECG, showing no clinically relevant deviations, as judged by the investigator (QTcF ≤450 ms) Exclusion Criteria: Subjects who have received any Investigational Medicinal Product in a clinical research study within the previous 3 months. History of any drug or alcohol abuse in the past 2 years Regular alcohol consumption in males >21 units per week Current smokers and those who have smoked within the last 12 months Positive drugs of abuse test result Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever, even inactive, is not allowed. Chronic infection or acute significant infection or fever within the previous 5 weeks prior to the start of IMP administration Malignancy or prior malignancy, with a disease-free interval of less than 5 years after diagnosis and intervention

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Single oral dose of EB8018<br>Single ascending doses, sequential group design | Drug: Single Ascending Doses of EB8018<br> <br> |
| Placebo Comparator: Single oral dose of placebo<br>Single doses, matching placebo | Drug: Single Ascending Doses of placebo<br> <br> |
| Experimental: Multiple oral doses of EB8018<br>Multiple ascending doses, daily for 14 days | Drug: Multiple Ascending Doses of EB8018<br> <br> |
| Placebo Comparator: Multiple oral doses of placebo<br>Multiple ascending doses, daily for 14 days | Drug: Multiple Ascending Doses of placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Treatment Related Adverse Event, including Abnormal Laboratory Events to evaluate the safety and tolerability profile of single ascending and multiple ascending doses of EB8018 compared with placebo in healthy subjects | The variables for analysis will be the difference of EB8018 compared with placebo for incidence, severity and type of adverse events, including changes in vital signs, physical examinations, laboratory safety tests and ECGs | Between screening and 7-10 days after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The amount of EB8018 in plasma | To characterize the amount of EB8018 in plasma over time - pharmacokinetics (PK) - after a single oral dose and multiple oral doses in healthy subjects | Between Day 1 predose and 48 hours after the (last) dose | 
| The amount of EB8018 in urine | To characterize the amount of EB8018 in urine over time - pharmacokinetics (PK) - after a single oral dose and multiple oral doses in healthy subjects | Between Day 1 predose and 48 hours after the (last) dose | 
| The amount of EB8018 in stool | To characterize the amount of EB8018 in urine over time - pharmacokinetics (PK) - after a single oral dose and multiple oral doses in healthy subjects | Between predose and 48 hours after the (last) dose | 
| Analysis of microbiome richness | To compare the abundance of gene richness, all phyla and certain species such as E. Coli | Between predose and 48 hours after the (last) dose |