Clinical trial NCT02998190: First-in-Human Single and Multiple Dose of EB8018
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Enterome
Sponsor class: INDUSTRY
Collaborators: name: Quotient Clinical
First posted: 2016-12-20
Enrollment: 60
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Between screening and 7-10 days after the last dose
Secondary outcomes:
measure: The amount of EB8018 in plasma
timeFrame: Between Day 1 predose and 48 hours after the (last) dose
measure: The amount of EB8018 in urine
timeFrame: Between Day 1 predose and 48 hours after the (last) dose
measure: The amount of EB8018 in stool
timeFrame: Between predose and 48 hours after the (last) dose
measure: Analysis of microbiome richness
timeFrame: Between predose and 48 hours after the (last) dose
Other outcomes:
Locations:
city: Ruddington
country: United Kingdom
facility: Quotient Clinical
state: Nottingham
Study officials:
References: