Healthy Volunteers
Conditions
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.
Interventions
DRUGVE303
The VE303 Drug Product is a live biotherapeutic product (LBP) consisting of 8 clonal human commensal bacterial strains manufactured under GMP conditions.
DRUGOral Vancomycin
Vancomycin, when taken by mouth, is used to treat Clostridium difficile-associated diarrhea.
Sponsors
Vedanta Biosciences, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Intervention model description
This Phase 1a/1b, first-in-human, open-label, single-center, dose-escalation study will evaluate the safety and microbiota changes induced by ingestion of VE303 following administration of oral vancomycin and VE303 administered without vancomycin pre-treatment in healthy adult subjects. Approximately 48 subjects are anticipated for enrollment, unless intermediate cohorts are required, in which case, up to an additional 18 subjects (for a total of approximately 66 subjects) may be enrolled.
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Outcome results
None listed