First-in-human Study of VE303 in Healthy Adult Volunteers

Phase 1

Completed

• Conditions: Healthy Volunteers
• Interventions: Drug: VE303; Drug: Oral Vancomycin

• Registration Number: NCT04236778
• Lead Sponsor: Vedanta Biosciences, Inc.

Brief Summary

This study was designed to evaluate safety and tolerability of a range of doses of VE303 in healthy adult volunteers. The study also evaluated pharmacokinetics of intestinal colonization by the VE303 strains and pharmacodynamics of recovery of the gut microbiota after administration of antibiotics followed by a course of VE303.

Detailed Description

VE303 is a rationally-defined bacterial consortium candidate being developed for the prevention of recurrent C. difficile infection. VE303 consists of 8 types of clonal human commensal bacteria strains selected for their ability to provide colonization resistance to C. difficile and manufactured under GMP conditions.

Study Timeline

• Study Start: 2017-11-28
• Primary Completion: 2019-03-11
• Study Completion: 2019-03-11
• Status Verified: 2020-01
• Study First Submitted: 2020-01-09
• Study First Submitted QC: 2020-01-16
• Study First Posted: 2020-01-22
• Last Update Submitted: 2020-01-22
• Last Update Posted: 2020-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

• Subjects who are judged to be in general good health
• Body mass index between 18.5 and 30 kg/m2
• Women either of non-child bearing potential or using a highly effective form of contraception
• Men using a highly effective method of contraception

Key

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Exclusion Criteria

• Past or present clinically significant diseases that may affect the outcome of the study
• Taking any medications, herbal preparations, or natural substances, live bacteria products, or food that impacts or alter GI flora
• Use of proton pump inhibitors or other short or long acting antacid medications
• Taking or has received an investigation drug or treatment within 60 days of inpatient admission
• Known allergies to involved study drugs
• Chronic constipation or diarrhea
• History of or active IBD

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 8	Oral Vancomycin	Cohort 8 received oral vancomycin followed by 10 doses of VE303 daily for 2 days, followed by 2 doses of VE303 daily for 3 days
Cohort 9	Oral Vancomycin	Cohort 8 received oral vancomycin followed by 10 doses of VE303 daily for 2 days, followed by 2 doses of VE303 daily for 3 days
Cohort 1	Oral Vancomycin	Cohort 1 received oral vancomycin followed by a single dose of VE303.
Cohort 7	Oral Vancomycin	Cohort 7 received oral vancomycin followed by 10 doses of VE303 daily for 2 days, followed by 2 doses of VE303 daily for 3 days
Cohort 3	Oral Vancomycin	Cohort 3 received oral vancomycin followed by a single day of 10 doses of VE303.
Cohort 4	Oral Vancomycin	Cohort 4 received oral vancomycin followed by 5 days of 10 doses daily of VE303.
Cohort 5	Oral Vancomycin	Cohort 5 received oral vancomycin followed by 14 days of 10 capsules daily of VE303
Vancomycin only	Oral Vancomycin	This cohort only received oral vancomycin.
Cohort 2	VE303	Cohort 2 received oral vancomycin followed by a single day of 5 doses of VE303.
Cohort 2	Oral Vancomycin	Cohort 2 received oral vancomycin followed by a single day of 5 doses of VE303.
Cohort 4	VE303	Cohort 4 received oral vancomycin followed by 5 days of 10 doses daily of VE303.
Cohort 5	VE303	Cohort 5 received oral vancomycin followed by 14 days of 10 capsules daily of VE303
Cohort 1	VE303	Cohort 1 received oral vancomycin followed by a single dose of VE303.
Cohort 3	VE303	Cohort 3 received oral vancomycin followed by a single day of 10 doses of VE303.
Cohort 6	VE303	Cohort 6 received 21 days of 10 doses daily of VE303
Cohort 7	VE303	Cohort 7 received oral vancomycin followed by 10 doses of VE303 daily for 2 days, followed by 2 doses of VE303 daily for 3 days
Cohort 8	VE303	Cohort 8 received oral vancomycin followed by 10 doses of VE303 daily for 2 days, followed by 2 doses of VE303 daily for 3 days
Cohort 9	VE303	Cohort 8 received oral vancomycin followed by 10 doses of VE303 daily for 2 days, followed by 2 doses of VE303 daily for 3 days

Primary Outcome Measures

Name	Time	Method
Safety of VE303 measured by incidence adverse events (AEs)	12 months post-dose	Measured in terms of incidence of AEs according to CTCAE V4.0
Tolerability of VE303 using modified PROMIS questionnaire (v1.0)	12 months post-dose	Characterized the highest well tolerated dose regimen of VE303 using modified PROMIS questionnaire (v1.0)

Secondary Outcome Measures

Name	Time	Method
Evaluate the colonization of the intestinal microbiota with VE303 component bacteria	12 months post-dose	Measurement of VE303 strain colonization in stool samples was performed using a metagenomic sequencing-based bioinformatic approach. A strain-specific marker panel was employed to characterize the relative abundance of VE303 strains in the intestinal microbiota.
Evaluate the changes in the intestinal microbiota due to VE303 dosing.	12 months post-dose	Measurement of intestinal microbiota due to VE303 dosing was performed using metagenomic sequencing- and metabolomic analysis-based approaches. Thus, focusing on taxonomic and functional changes occurring in the gut.
Evaluate the metabolomic changes in stool due to VE303 dosing.	12 months post-dose	Quantified changes in pool of metabolite levels (bile acids and short-chain fatty acids) from stool samples

Trial Locations

Locations (1)

Pharmaron CPC; 🇺🇸 Baltimore, Maryland, United States