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

• ClinicalTrials.gov Identifier: NCT04236778
• Recruitment Status: Completed
• First Posted: January 22, 2020
• Last Update Posted: January 27, 2020
• Sponsor: Vedanta Biosciences, Inc.
• Information provided by (Responsible Party): Vedanta Biosciences, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers	Drug: VE303; Drug: Oral Vancomycin	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 39 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• 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.
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: 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
• Actual Study Start Date: November 28, 2017
• Actual Primary Completion Date: March 11, 2019
• Actual Study Completion Date: March 11, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

United States, Maryland

Pharmaron CPC

Baltimore, Maryland, United States, 21201

Sponsors and Collaborators

Vedanta Biosciences, Inc.

More Information

• Responsible Party: Vedanta Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT04236778
• Other Study ID Numbers: VE303-01
• First Posted: January 22, 2020
• Last Update Posted: January 27, 2020
• Last Verified: January 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Vancomycin; Anti-Bacterial Agents; Anti-Infective Agents