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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04236778
Recruitment Status : Completed
First Posted : January 22, 2020
Last Update Posted : January 27, 2020
Sponsor:
Information provided by (Responsible Party):
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.

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.

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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

Resource links provided by the National Library of Medicine


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.




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



Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04236778


Locations
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United States, Maryland
Pharmaron CPC
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
Vedanta Biosciences, Inc.

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Responsible Party: Vedanta Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT04236778    
Other Study ID Numbers: VE303-01
First Posted: January 22, 2020    Key Record Dates
Last Update Posted: January 27, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents