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

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: NCT03576183
Recruitment Status : Completed
First Posted : July 3, 2018
Last Update Posted : December 7, 2018
Sponsor:
Collaborators:
Johns Hopkins University
Naval Medical Research Center
Information provided by (Responsible Party):
Valneva Austria GmbH

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.

Condition or disease Intervention/treatment Phase
Enterotoxigenic Escherichia Coli Infection Diarrhea Biological: VLA1701 Biological: Placebo Other: Challenge Strain Phase 2

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+, ST-, 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Randomized Double-Blinded Pilot Study Confirming A Human Challenge Model Using LSN03-016011/A Expressing LT And CS17 And Investigating The Safety Of VLA1701 (An Investigational Oral Cholera And ETEC Vaccine)
Actual Study Start Date : June 4, 2018
Actual Primary Completion Date : June 26, 2018
Actual Study Completion Date : November 30, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: 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.

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

Other: Challenge Strain
LSN03-016011/A

Placebo Comparator: Placebo

The buffer component of VLA1701 will be used as Placebo.

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

Biological: Placebo
buffer component of VLA1701

Other: Challenge Strain
LSN03-016011/A




Primary Outcome Measures :
  1. Percentage of subjects with severe to moderate diarrhea [ Time Frame: 5 days after challenge ]
    within 120 hours of challenge with ETEC strain LSN03-016011/A.


Secondary Outcome Measures :
  1. Calculation of disease severity score after challenge with ETEC strain LSN03-016011/ A [ Time Frame: 7 days after challenge ]

    ETEC diarrhea disease severity score with a score ranging from 0 (no disease) to 8 (most severe disease) utilizing objective signs, subjective Symptoms and stool Output.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4777366/table/pone.0149358.t005/


  2. Percentage of subjects with solicited adverse events [ Time Frame: 7days after each vaccination ]
  3. Percentage of subjects with any adverse events [ Time Frame: up to Visit 4 (day of challenge, 23 days post first vaccination) ]
  4. Percentage of subjects with serious adverse events [ Time Frame: up to Visit 4 (day of challenge, 23 days post first vaccination) ]
  5. percentage of subjects with any IMP related adverse events [ Time Frame: up to Visit 4 (day of challenge, 23 days post first vaccination) ]
  6. percentage of subjects with IMP-related serious adverse events [ Time Frame: up to Visit 4 (day of challenge, 23 days post first vaccination) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 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.

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): NCT03576183


Locations
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United States, Maryland
Department of International Health Johns Hopkins University
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Valneva Austria GmbH
Johns Hopkins University
Naval Medical Research Center
Investigators
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Study Director: Christian Taucher, PhD Valneva Austria GmbH
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Responsible Party: Valneva Austria GmbH
ClinicalTrials.gov Identifier: NCT03576183    
Other Study ID Numbers: VLA1701-201
First Posted: July 3, 2018    Key Record Dates
Last Update Posted: December 7, 2018
Last Verified: December 2018
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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Escherichia coli Infections
Diarrhea
Signs and Symptoms, Digestive
Enterobacteriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections