First-in-Human Single and Multiple Dose of EB8018

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.

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Single Ascending Doses of EB8018; Drug: Single Ascending Doses of placebo; Drug: Multiple Ascending Doses of EB8018; Drug: Multiple Ascending Doses of placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington, Nottingham, United Kingdom, NG11 6JS
      • Quotient Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single oral dose of EB8018; Single ascending doses, sequential group design	Drug: Single Ascending Doses of EB8018
PLACEBO_COMPARATOR: Single oral dose of placebo; Single doses, matching placebo	Drug: Single Ascending Doses of placebo
EXPERIMENTAL: Multiple oral doses of EB8018; Multiple ascending doses, daily for 14 days	Drug: Multiple Ascending Doses of EB8018
PLACEBO_COMPARATOR: Multiple oral doses of placebo; Multiple ascending doses, daily for 14 days	Drug: Multiple Ascending Doses of placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Enterome
• Collaborators: Quotient Clinical

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2016
• Primary Completion (ACTUAL): April 1, 2017
• Study Completion (ACTUAL): August 1, 2017

Study Registration Dates

• First Submitted: December 13, 2016
• First Submitted That Met QC Criteria: December 15, 2016
• First Posted (ESTIMATE): December 20, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2018
• Last Update Submitted That Met QC Criteria: February 12, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: EBFIM116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO