Study Confirming A Human Challenge Model and Investigating The Safety Of VLA1701

NCT ID: NCT03576183

Last Updated: 2021-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-04
• Study Completion Date: 2018-11-30

Brief Summary

This is a single-center, double-blind, placebo-controlled, Phase II vaccination and challenge study designed to confirm a human challenge model with E. coli strain LSN03-016011/A.

Detailed Description

This is a single-center, double-blind, placebo-controlled, Phase II vaccination and challenge study designed to confirm a human challenge model with E. coli strain LSN03-016011/A (LT+ (Labile toxin), ST- (Stable toxin), CS17), as well as collect expanded safety and immunogenicity data.

The study will be carried out in two phases:

Vaccination phase: up to 34 subjects will be randomized 1:1 to receive 2 doses of either VLA1701 or placebo orally. The doses will be given 7 days apart and subjects will be followed as an outpatient for safety.

Challenge Phase: 30 Subjects, out of the 34 subjects, will be challenged.

After challenge, subjects will be monitored for diarrhea and other signs/symptoms of enteric illness by daily medical checks, vital sign determinations, grading and weighing of all stools.

Conditions

Enterotoxigenic Escherichia Coli Infection; Diarrhea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

VLA1701

VLA1701 is an investigational oral vaccine against LT-ETEC (Labile Toxin-Enterotoxigenic E coli)

The vaccine is administered orally in 2 doses about 1 week apart.

Group Type: ACTIVE_COMPARATOR

VLA1701

Intervention Type: BIOLOGICAL

VLA1701 is an investigational oral vaccine against LT-ETEC (Labile Toxin-Enterotoxigenic E coli)

Challenge Strain

Intervention Type: OTHER

LSN03-016011/A

Placebo

The buffer component of VLA1701 will be used as Placebo.

The vaccine is administered orally in 2 doses about 1 week apart.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: BIOLOGICAL

buffer component of VLA1701

Challenge Strain

Intervention Type: OTHER

LSN03-016011/A

Interventions

VLA1701

VLA1701 is an investigational oral vaccine against LT-ETEC (Labile Toxin-Enterotoxigenic E coli)

Intervention Type: BIOLOGICAL

Placebo

buffer component of VLA1701

Intervention Type: BIOLOGICAL

Challenge Strain

LSN03-016011/A

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Healthy male and non-pregnant female subjects aged 18 to <50 years;

2. BMI of 19.0 to 35.0 kg/m2

3. Willingness to participate after informed consent has been obtained from the subject prior to any study related procedures.

4. Completion of a training session and demonstration of comprehension of the protocol procedures and knowledge of ETEC-associated illness by passing a written examination.

5. If subject is of childbearing potential:

1. Negative pregnancy test at screening with understanding to not become pregnant within 28 days after challenge;

2. Subject has practiced an effective method of contraception during the 30 days before screening (Visit 0);

3. Subject agrees to employ adequate birth control measures for the duration of the study.

Exclusion Criteria

1. Participated in research involving investigational product within 30 days before planned date of first vaccination or planned use through Day 44;

2. Any prior exposure to ETEC (including LSN03-016011/A) or cholera occupationally or received LT (Or any mutant forms of LT (e.g., LTR192G, LTR192GL211A), ETEC, or cholera vaccine);

3. Subjects with known abnormal stooling patterns (fewer than 3 per week or more than 3 per day);

4. Known allergies to any component of the vaccine;

5. Subjects with known allergies to more than 1 planned antibiotics:

6. History of diarrhea while traveling in a developing country within the last 3 years;

7. Subjects whose occupation involves handling of ETEC or cholera bacteria;

8. Women who are pregnant or breastfeeding;

9. Significant medical conditions including chronic, immunosuppressive, malignant, or gastrointestinal diseases (e.g. History of Irritable Bowel Syndrome (as defined by the Rome III criteria or medical diagnosis) or gastric ulcer disease) or enteric, pulmonary, cardiac, liver or renal disease. Some medical conditions which are adequately treated and stable may be acceptable in the study (e.g. hypertension);

10. Significant abnormalities in screening lab hematology or serum chemistries;

11. Use of any medication known to effect the immune system (e.g. systemic corticosteroids) within 30 days of vaccination or planned use during active study period (excluding inhaled steroids);

12. Evidence of confirmed infection with HIV, Hepatitis B or Hepatitis C;

13. Subjects with IgA (Immunoglobulin A) deficiency (serum IgA < 7 mg/dl or limit of detection of assay);

14. Regular use of antacids, antidiarrheal, loperamide, bismuth subsalicylate, diphenoxylate or similar medication less than 2 weeks prior to enrolling in the study and through the inpatient portion of the study;

15. Known or suspected alcohol abuse or illicit drug use within the last year, positive urine toxicology for drugs of abuse;

16. Persons who are committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities);

17. Persons who are in a dependent relationship with the sponsor, an investigator or other study team members, or the study center.

18. Any other criteria which, in the investigator's opinion, would compromise the ability of the subject to participate in the study, the safety of the study, or the results of the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: collaborator

Naval Medical Research Center

FED

Sponsor Role: collaborator

Valneva Austria GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Taucher, PhD

Role: STUDY_DIRECTOR

Valneva Austria GmbH

Locations

Department of International Health Johns Hopkins University

Baltimore, Maryland, United States

Countries

United States

References

Talaat KR, Porter CK, Chakraborty S, Feijoo BL, Brubaker J, Adjoodani BM, DeNearing B, Prouty MG, Poole ST, Bourgeois AL, Billingsley M, Sack DA, Eder-Lingelbach S, Taucher C. Validation of a Human Challenge Model Using an LT-Expressing Enterotoxigenic E. coli Strain (LSN03-016011) and Characterization of Potential Amelioration of Disease by an Investigational Oral Vaccine Candidate (VLA1701). Microorganisms. 2024 Apr 3;12(4):727. doi: 10.3390/microorganisms12040727.

Reference Type: DERIVED

PMID: 38674674 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

VLA1701-201

Identifier Type: -

Identifier Source: org_study_id