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

A Phase 1a/1b, First-in-human, Open-label Study of Escalating Doses of VE303 in Healthy Adult Volunteers With or Without Vancomycin Pre-treatment to Evaluate Safety, Dosing, and Pharmacodynamics

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: VE303; Drug: Oral Vancomycin

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 Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Pharmaron CPC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Key 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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cohort 1; Cohort 1 received oral vancomycin followed by a single dose of VE303.	Drug: VE303; The VE303 Drug Product is a live biotherapeutic product (LBP) consisting of 8 clonal human commensal bacterial strains manufactured under GMP conditions.; Drug: Oral Vancomycin; Vancomycin, when taken by mouth, is used to treat Clostridium difficile-associated diarrhea.
EXPERIMENTAL: Cohort 2; Cohort 2 received oral vancomycin followed by a single day of 5 doses of VE303.	Drug: VE303; The VE303 Drug Product is a live biotherapeutic product (LBP) consisting of 8 clonal human commensal bacterial strains manufactured under GMP conditions.; Drug: Oral Vancomycin; Vancomycin, when taken by mouth, is used to treat Clostridium difficile-associated diarrhea.
EXPERIMENTAL: Cohort 3; Cohort 3 received oral vancomycin followed by a single day of 10 doses of VE303.	Drug: VE303; The VE303 Drug Product is a live biotherapeutic product (LBP) consisting of 8 clonal human commensal bacterial strains manufactured under GMP conditions.; Drug: Oral Vancomycin; Vancomycin, when taken by mouth, is used to treat Clostridium difficile-associated diarrhea.
EXPERIMENTAL: Cohort 4; Cohort 4 received oral vancomycin followed by 5 days of 10 doses daily of VE303.	Drug: VE303; The VE303 Drug Product is a live biotherapeutic product (LBP) consisting of 8 clonal human commensal bacterial strains manufactured under GMP conditions.; Drug: Oral Vancomycin; Vancomycin, when taken by mouth, is used to treat Clostridium difficile-associated diarrhea.
EXPERIMENTAL: Cohort 5; Cohort 5 received oral vancomycin followed by 14 days of 10 capsules daily of VE303	Drug: VE303; The VE303 Drug Product is a live biotherapeutic product (LBP) consisting of 8 clonal human commensal bacterial strains manufactured under GMP conditions.; Drug: Oral Vancomycin; Vancomycin, when taken by mouth, is used to treat Clostridium difficile-associated diarrhea.
EXPERIMENTAL: Cohort 6; Cohort 6 received 21 days of 10 doses daily of VE303	Drug: VE303; The VE303 Drug Product is a live biotherapeutic product (LBP) consisting of 8 clonal human commensal bacterial strains manufactured under GMP conditions.
EXPERIMENTAL: Cohort 7; 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	Drug: VE303; The VE303 Drug Product is a live biotherapeutic product (LBP) consisting of 8 clonal human commensal bacterial strains manufactured under GMP conditions.; Drug: Oral Vancomycin; Vancomycin, when taken by mouth, is used to treat Clostridium difficile-associated diarrhea.
EXPERIMENTAL: Cohort 8; 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	Drug: VE303; The VE303 Drug Product is a live biotherapeutic product (LBP) consisting of 8 clonal human commensal bacterial strains manufactured under GMP conditions.; Drug: Oral Vancomycin; Vancomycin, when taken by mouth, is used to treat Clostridium difficile-associated diarrhea.
EXPERIMENTAL: Cohort 9; 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	Drug: VE303; The VE303 Drug Product is a live biotherapeutic product (LBP) consisting of 8 clonal human commensal bacterial strains manufactured under GMP conditions.; Drug: Oral Vancomycin; Vancomycin, when taken by mouth, is used to treat Clostridium difficile-associated diarrhea.
PLACEBO_COMPARATOR: Vancomycin only; This cohort only received oral vancomycin.	Drug: Oral Vancomycin; Vancomycin, when taken by mouth, is used to treat Clostridium difficile-associated diarrhea.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the colonization of the intestinal microbiota with VE303 component bacteria	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.	12 months post-dose
Evaluate the changes in the intestinal microbiota due to VE303 dosing.	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.	12 months post-dose
Evaluate the metabolomic changes in stool due to VE303 dosing.	Quantified changes in pool of metabolite levels (bile acids and short-chain fatty acids) from stool samples	12 months post-dose

Collaborators and Investigators

• Sponsor: Vedanta Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 28, 2017
• Primary Completion (ACTUAL): March 11, 2019
• Study Completion (ACTUAL): March 11, 2019

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 16, 2020
• First Posted (ACTUAL): January 22, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 27, 2020
• Last Update Submitted That Met QC Criteria: January 22, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: VE303-01

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No