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

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)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03576183

Enrollment

Registered

2018-07-03

Start date

2018-06-04

Completion date

2018-11-30

Last updated

2021-04-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diarrhea, Enterotoxigenic Escherichia Coli Infection

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.

Interventions

BIOLOGICALVLA1701

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

BIOLOGICALPlacebo

buffer component of VLA1701

OTHERChallenge Strain

LSN03-016011/A

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Investigator)

Masking description

Double (Participant, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 49 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

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

Secondary

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

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. VLA1701: VLA1701 is an investigational oral vaccine against LT-ETEC (Labile Toxin-Enterotoxigenic E coli) Challenge Strain: LSN03-016011/A	15
Placebo The buffer component of VLA1701 will be used as Placebo. The vaccine is administered orally in 2 doses about 1 week apart. Placebo: buffer component of VLA1701 Challenge Strain: LSN03-016011/A	15
Total	30

Baseline characteristics

Characteristic	Placebo	Total	VLA1701
Age, Continuous	35.1 years STANDARD_DEVIATION 9.09	35.1 years STANDARD_DEVIATION 8.37	35.2 years STANDARD_DEVIATION 7.89
Race/Ethnicity, Customized American Indian or Alaskan Native	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Black or African American	11 Participants	25 Participants	14 Participants
Race/Ethnicity, Customized Other: Latino / Hispanic	1 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized Other: Multi-racial	1 Participants	1 Participants	0 Participants
Race/Ethnicity, Customized White	2 Participants	2 Participants	0 Participants
Sex: Female, Male Female	7 Participants	10 Participants	3 Participants
Sex: Female, Male Male	8 Participants	20 Participants	12 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 17	0 / 17
other Total, other adverse events	10 / 17	13 / 17
serious Total, serious adverse events	0 / 17	0 / 17

Outcome results

Primary

Percentage of Subjects With Moderate to Severe Diarrhea

within 120 hours of challenge with ETEC strain LSN03-016011/A.

Time frame: 5 days after challenge

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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
VLA1701	Percentage of Subjects With Moderate to Severe Diarrhea	7 Participants
Placebo	Percentage of Subjects With Moderate to Severe Diarrhea	11 Participants

Secondary

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.

Time frame: 7 days after challenge

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

Arm	Measure	Value (MEAN)	Dispersion
VLA1701	Disease Severity Score After Challenge With ETEC Strain LSN03-016011/ A	2.3 units on a scale	Standard Deviation 1.7
Placebo	Disease Severity Score After Challenge With ETEC Strain LSN03-016011/ A	3.7 units on a scale	Standard Deviation 1.9

Secondary