Enterotoxigenic Escherichia Coli InfectionPhase 2NCT03576183

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

A Phase 2 study testing VLA1701 and Challenge Strain in people with Enterotoxigenic Escherichia Coli Infection and Diarrhea, run by Valneva Austria GmbH at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 49 yearsHealthy volunteers can take part
Conditions the study is for: Enterotoxigenic Escherichia Coli Infection, Diarrhea
What is being tested?: VLA1701 and Challenge Strain
Type of treatment: Vaccines, Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 34 participants
Where: 1 siteUnited States
Study dates: 4 Jun 2018to 30 Nov 2018
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 49 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy male and non-pregnant female subjects aged 18 to <50 years;
BMI of 19.0 to 35.0 kg/m2
Willingness to participate after informed consent has been obtained from the subject prior to any study related procedures.
Completion of a training session and demonstration of comprehension of the protocol procedures and knowledge of ETEC-associated illness by passing a written examination.
If subject is of childbearing potential:
Negative pregnancy test at screening with understanding to not become pregnant within 28 days after challenge;
Subject has practiced an effective method of contraception during the 30 days before screening (Visit 0);
Subject agrees to employ adequate birth control measures for the duration of the study.

Who cannot join

Participated in research involving investigational product within 30 days before planned date of first vaccination or planned use through Day 44;
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);
Subjects with known abnormal stooling patterns (fewer than 3 per week or more than 3 per day);
Known allergies to any component of the vaccine;
Subjects with known allergies to more than 1 planned antibiotics:
History of diarrhea while traveling in a developing country within the last 3 years;

Show all 18Show fewer

Subjects whose occupation involves handling of ETEC or cholera bacteria;
Women who are pregnant or breastfeeding;
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);
Significant abnormalities in screening lab hematology or serum chemistries;
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);
Evidence of confirmed infection with HIV, Hepatitis B or Hepatitis C;
Subjects with IgA (Immunoglobulin A) deficiency (serum IgA < 7 mg/dl or limit of detection of assay);
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;
Known or suspected alcohol abuse or illicit drug use within the last year, positive urine toxicology for drugs of abuse;
Persons who are committed to an institution (by virtue of an order issued either by the judicial or the administrative authorities);
Persons who are in a dependent relationship with the sponsor, an investigator or other study team members, or the study center.
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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Department of International Health Johns Hopkins University
Baltimore, Maryland, 21205

Other trials in United States

About this study

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 (Enterotoxigenic E Coli) (Vaccine)

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.

Read the detailed description

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
Being tested: VLA1701, Placebo, Challenge Strain
Medical subject headings: Diarrhea

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VLA1701Biological
VLA1701 is an investigational oral vaccine against LT-ETEC (Labile Toxin-Enterotoxigenic E coli)
PlaceboBiological
buffer component of VLA1701
Challenge StrainOther
LSN03-016011/A

Study groups in NCT03576183
Study group	Role	What they receive
VLA1701	Active comparator	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. Receives: Biological: VLA1701; Other: Challenge Strain
Placebo	Placebo comparator	The buffer component of VLA1701 will be used as Placebo. The vaccine is administered orally in 2 doses about 1 week apart. Receives: Biological: Placebo; Other: Challenge Strain

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Subjects With Moderate to Severe Diarrhea
within 120 hours of challenge with ETEC strain LSN03-016011/A.
Measured: 5 days after challenge

Secondary outcomes (6)

Disease Severity Score After Challenge With ETEC Strain LSN03-016011/ A
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.
Measured: 7 days after challenge
Percentage of Subjects With Solicited Adverse Events
adverse events covered by the subjects memory card
Measured: 7days after each vaccination
Percentage of Subjects With Any Adverse Events (AE)
Measured: until Month 6
Number of Subjects With Serious Adverse Events
Measured: until Month 6
Percentage of Subjects With Any IMP (Investigational Medicinal Product) Related Adverse Events
unsolicited events
Measured: up to Visit 4 (day of challenge, 23 days post first vaccination)
Percentage of Subjects With IMP-related Serious Adverse Events
Measured: up to Visit 4 (day of challenge, 23 days post first vaccination)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 Jun 201830 Nov 2018

First posted3 Jul 2018
Study start4 Jun 2018
Primary completion26 Jun 2018
Study completion30 Nov 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Enterotoxigenic Escherichia Coli InfectionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03576183
Sponsor's protocol ID: VLA1701-201
Status last verified: Mar 2021
First submitted: 15 May 2018
Last updated: 23 Apr 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 38674674

Study at a glance

From the registry record, last updated by the sponsor on 23 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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 (Enterotoxigenic E Coli) (Vaccine)
ClinicalTrials.gov ID: NCT03576183
Acronym / sponsor ID: VLA1701-201
Conditions: Enterotoxigenic Escherichia Coli Infection, Diarrhea
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: Valneva Austria GmbHIndustry (pharma, biotech, devices)
Collaborators: Johns Hopkins University, Naval Medical Research Center
Study start: 4 Jun 2018 (actual)
Primary completion: 26 Jun 2018 (actual)
Study completion: 30 Nov 2018 (actual)
First posted: 3 Jul 2018 (actual)
Results: Posted 23 Apr 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

The study will be carried out in two phases:

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.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
VLA1701	Active comparator	Biological: VLA1701, Other: Challenge StrainVLA1701 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.
Placebo	Placebo comparator	Biological: Placebo, Other: Challenge StrainThe buffer component of VLA1701 will be used as Placebo. The vaccine is administered orally in 2 doses about 1 week apart.

Who may qualify

Ages: 18 to 49 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (8 listed)

Healthy male and non-pregnant female subjects aged 18 to <50 years;
BMI of 19.0 to 35.0 kg/m2
Willingness to participate after informed consent has been obtained from the subject prior to any study related procedures.
Completion of a training session and demonstration of comprehension of the protocol procedures and knowledge of ETEC-associated illness by passing a written examination.
If subject is of childbearing potential:

Key exclusion criteria (18 listed)

Participated in research involving investigational product within 30 days before planned date of first vaccination or planned use through Day 44;
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);
Subjects with known abnormal stooling patterns (fewer than 3 per week or more than 3 per day);
Known allergies to any component of the vaccine;
Subjects with known allergies to more than 1 planned antibiotics:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VLA1701VLA1701 is an investigational oral vaccine against LT-ETEC (Labile Toxin-Enterotoxigenic E coli)	Biological	VLA1701
Placebobuffer component of VLA1701	Biological	Placebo
Challenge StrainLSN03-016011/A	Other	Placebo, VLA1701

Primary outcome

Percentage of Subjects With Moderate to Severe Diarrhea
Time frame: 5 days after challenge
within 120 hours of challenge with ETEC strain LSN03-016011/A.

6 secondary outcomes

Disease Severity Score After Challenge With ETEC Strain LSN03-016011/ A
Time frame: 7 days after challenge
Percentage of Subjects With Solicited Adverse Events
Time frame: 7days after each vaccination
Percentage of Subjects With Any Adverse Events (AE)
Time frame: until Month 6
Number of Subjects With Serious Adverse Events
Time frame: until Month 6
Percentage of Subjects With Any IMP (Investigational Medicinal Product) Related Adverse Events
Time frame: up to Visit 4 (day of challenge, 23 days post first vaccination)
Percentage of Subjects With IMP-related Serious Adverse Events
Time frame: up to Visit 4 (day of challenge, 23 days post first vaccination)

Results and safety

Results posted to the registry on 23 Apr 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
VLA1701	17	15
Placebo	17	16

Primary outcome: Percentage of Subjects With Moderate to Severe Diarrhea

Time frame: 5 days after challenge. Count of participants. Unit: Participants

Measure	VLA1701 n = 15	Placebo n = 15
Value	7	11

Population analysed: Challenge Population = all subjects who received two doses of the vaccine and the challenge dose

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: until Month 6. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
VLA1701	0 of 17 (0%)	10 of 17 (58.8%)	0 of 17
Placebo	0 of 17 (0%)	13 of 17 (76.5%)	0 of 17

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 38674674Talaat 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.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Christian Taucher, PhD study director

Valneva Austria GmbH

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VLA1701 and Challenge Strain in people with Enterotoxigenic Escherichia Coli Infection and Diarrhea, run by Valneva Austria GmbH at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Subjects With Moderate to Severe Diarrhea (time frame: 5 days after challenge). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03576183, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2021.