Shigella Sonnei DysenteriesPhase 2NCT03038243
Safety, Immunogenicity and Efficacy Study of Inactivated Whole Cell Shigella Flexneri 2a Vaccine With and Without dmLT in Adults
A Phase 2 study testing Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT) and Shigella flexneri 2a whole cell (Sf2aWC) vaccine in people with Shigella Sonnei Dysenteries, run by PATH at 1 site in United States.
Trial summary
This is a research study about an experimental (investigational) oral inactivated whole cell Shigella flexneri 2a killed vaccine (Sf2aWC) and an adjuvant called dmLT. Sf2aWC is a killed vaccine that is being made to prevent disease from Shigella., which causes bloody, watery diarrhea. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Shigella Sonnei Dysenteries
- What is being tested?
- Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT) and Shigella flexneri 2a whole cell (Sf2aWC) vaccine
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2017to 31 Dec 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults, male or female, age 18 to 45 years (inclusive) at the time of enrollment.
- General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of PI.
- Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
- Completion of a training session and demonstrated comprehension of the protocol procedures and knowledge of Shigella associated illness by passing a written examination (70% pass score).
- Availability for the study duration, including all planned follow-up visits.
Who cannot join
- Presence of a significant medical or psychiatric condition that in the opinion of the investigator precludes participation in the study. Some medical conditions that are adequately treated and stable would not preclude entry into the study. These conditions might include stable asthma controlled with inhalers or mild hypertension stably controlled with a single agent.
- Significant abnormalities in screening hematology, or serum chemistry as determined by PI or PI in consultation with the Medical Officer and sponsor.
- Recent of a non-study vaccine or receipt of another investigational product (within 14 days before vaccination).
- Have household contacts who are <3 years old or >70 years old or infirm or immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer chemotherapy, or other chronic debilitating disease).
- Use of any medication that affects the immune function (e.g., corticosteroids and others) within 30 days preceding the first vaccination or planned use during the active study period.
- Symptoms of Traveler's diarrhea associated with travel to countries where Shigella or other enteric infections are endemic (most of the developing world) within 1 year prior to dosing.
- History of shigellosis or Shigella vaccination or challenge or a laboratory worker with known exposure to Shigella within the last 6 months
- Prior receipt of experimental Shigella vaccine or live Shigella challenge within 3 years.
Trial locations and contacts
1 site in 1 country.
United States1 site
Center for Vaccine Development (CVD), University of Maryland School of Medicine
Baltimore, Maryland, 21201
About this study
Official title: A Phase 2a/2b, Randomized, Double-blinded, Placebo-controlled, Trial to Assess the Safety, Immunogenicity and Efficacy of Inactivated Shigella Flexneri 2a Whole Cell (Sf2aWC) Vaccine Administered With and Without Double Mutant E. Coli Heat Labile Toxin (dmLT) in Healthy Adult Subjects
This is a research study about an experimental (investigational) oral inactivated whole cell Shigella flexneri 2a killed vaccine (Sf2aWC) and an adjuvant called dmLT. Sf2aWC is a killed vaccine that is being made to prevent disease from Shigella., which causes bloody, watery diarrhea. An adjuvant is something that is added to a vaccine to make it work better. The purpose of the study is to see if the vaccine will protect people from Shigella infection with or without an adjuvant called dmLT. About 72 healthy adults, ages 18-45, will participate in this study. The study will compare 2 different vaccination groups and 1 control group. Volunteers have an equal chance to be in any of the 3 groups. Study procedures include: stool samples, blood samples and documenting side effects. Participants will be involved in study related procedures for about 6 months.
Read the detailed description
Despite the public health burden of Shigella spp. on travelers, deployed soldiers and, most significantly, young children in the developing world, there is no licensed vaccine against Shigella. The rationale for using Shigella flexneri 2a whole cell killed vaccine (Sf2aWC), is that it is expected to be especially well tolerated by subjects. This is a single site, 2a/2b, double-blind, randomized, placebo-controlled, study in healthy adult subjects. Approximately 72 subjects will be enrolled into one of three vaccination groups: Sf2aWC 1011 Sf2aWC cells plus 10 µg dmLT (Group 1, n=24), 1011 Sf2WC cells alone (Group 2, n=24); or placebo (Group 4, n=24). The placebo preparation will be bicarbonate buffer.
After the vaccination phase subjects will be admitted by cohort on day 84 to an inpatient facility for 12 days to undergo challenge with approximately 1500 colony forming units (CFU) of wild type S. flexneri 2a strain 2457T (administered with NaHCO3 buffer). After 5 days of observation for clinical endpoints (or earlier and within 12 hours if they meet the definition of moderate-to-severe shigellosis as defined in the primary endpoints section below), subjects will receive a 5-day course of orally administered ciprofloxacin.
The primary objective of this study are to 1) evaluate, the safety and reactogenicity of 3 oral sequential doses of Sf2aWC with or without dmLT, 2) To measure the protective efficacy of 3 spaced doses of high-dose Sf2aWC vaccine with and without dmLT against moderate-to-severe shigellosis following experimental oral challenge with wild-type S. flexneri 2a 2457T
- Conditions
- Shigella Sonnei Dysenteries
- Being tested
- Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT), Shigella flexneri 2a whole cell (Sf2aWC) vaccine, Placebo
- Keywords
- Shigella, vaccine, shigellosis, dysentery, whole cell
- Medical subject headings
- Dysentery, Bacillary, Dysentery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT)Biological
2.25 x 10^11 Sf2aWC cells +10 µg dmLT administered orally on Days 0, 28, and 56
Shigella flexneri 2a whole cell (Sf2aWC) vaccineBiological
2.25 x 10^11 Sf2WC cells administered orally on Days 0, 28, and 56
PlaceboOther
2.0 grams of NaHCO3 dissolved in 150 mL of sterile water
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Group 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water Receives: Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT); Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine; Other: Placebo |
| Cohort 2 | Experimental | Group 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water Receives: Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT); Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine; Other: Placebo |
| Cohort 3 | Experimental | Group 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water Receives: Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT); Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
solicited reactions, AEs, SAEs
solicited reactions, AEs, SAEs assessed post-vaccination using targeted physical examinations, vital signs, and clinical laboratory tests
Measured: first vaccination through 6 months post-3rd vaccination
prevention of moderate to severe shigellosis
prevention of moderate to severe shigellosis identified by diarrhea, fever, dysentery, and other signs/symptoms of enteric illness
Measured: up to 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2017 (estimated)
- Study start1 Aug 2017 (estimated)
- Primary completion31 Dec 2018 (estimated)
- Study completion31 Dec 2019 (estimated)
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Shigella Sonnei DysenteriesStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Wilbur Chen, MD, MS, Principal investigator, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03038243
- Sponsor's protocol ID
- VAC-047
- Status last verified
- Nov 2017
- First submitted
- 23 Jan 2017
- Last updated
- 20 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a/2b, Randomized, Double-blinded, Placebo-controlled, Trial to Assess the Safety, Immunogenicity and Efficacy of Inactivated Shigella Flexneri 2a Whole Cell (Sf2aWC) Vaccine Administered With and Without Double Mutant E. Coli Heat Labile Toxin (dmLT) in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT03038243
- Acronym / sponsor ID
- VAC-047
- Conditions
- Shigella Sonnei Dysenteries
- Keywords
- Shigella, vaccine, shigellosis, dysentery, whole cell
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Lack of funding
- Enrolment
- 0 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Study start
- 1 Aug 2017 (estimated)
- Primary completion
- 31 Dec 2018 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 31 Jan 2017 (estimated)
- Results
- Not posted in the source record
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 research study about an experimental (investigational) oral inactivated whole cell Shigella flexneri 2a killed vaccine (Sf2aWC) and an adjuvant called dmLT. Sf2aWC is a killed vaccine that is being made to prevent disease from Shigella., which causes bloody, watery diarrhea. An adjuvant is something that is added to a vaccine to make it work better. The purpose of the study is to see if the vaccine will protect people from Shigella infection with or without an adjuvant called dmLT. About 72 healthy adults, ages 18-45, will participate in this study. The study will compare 2 different vaccination groups and 1 control group. Volunteers have an equal chance to be in any of the 3 groups. Study procedures include: stool samples, blood samples and documenting side effects. Participants will be involved in study related procedures for about 6 months.
Detailed description
Despite the public health burden of Shigella spp. on travelers, deployed soldiers and, most significantly, young children in the developing world, there is no licensed vaccine against Shigella. The rationale for using Shigella flexneri 2a whole cell killed vaccine (Sf2aWC), is that it is expected to be especially well tolerated by subjects. This is a single site, 2a/2b, double-blind, randomized, placebo-controlled, study in healthy adult subjects. Approximately 72 subjects will be enrolled into one of three vaccination groups: Sf2aWC 1011 Sf2aWC cells plus 10 µg dmLT (Group 1, n=24), 1011 Sf2WC cells alone (Group 2, n=24); or placebo (Group 4, n=24). The placebo preparation will be bicarbonate buffer.
After the vaccination phase subjects will be admitted by cohort on day 84 to an inpatient facility for 12 days to undergo challenge with approximately 1500 colony forming units (CFU) of wild type S. flexneri 2a strain 2457T (administered with NaHCO3 buffer). After 5 days of observation for clinical endpoints (or earlier and within 12 hours if they meet the definition of moderate-to-severe shigellosis as defined in the primary endpoints section below), subjects will receive a 5-day course of orally administered ciprofloxacin.
The primary objective of this study are to 1) evaluate, the safety and reactogenicity of 3 oral sequential doses of Sf2aWC with or without dmLT, 2) To measure the protective efficacy of 3 spaced doses of high-dose Sf2aWC vaccine with and without dmLT against moderate-to-severe shigellosis following experimental oral challenge with wild-type S. flexneri 2a 2457T
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT), Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine, Other: PlaceboGroup 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water |
| Cohort 2 | Experimental | Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT), Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine, Other: PlaceboGroup 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water |
| Cohort 3 | Experimental | Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT), Biological: Shigella flexneri 2a whole cell (Sf2aWC) vaccine, Other: PlaceboGroup 1, 2.25 x 10^11 Sf2aWC cells +10 µg dmLT Group 2, 2.25 x 10^11 Sf2WC cells Group 3, 2.0 grams of NaHCO3 dissolved in 150 mL of sterile water |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy adults, male or female, age 18 to 45 years (inclusive) at the time of enrollment.
- General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of PI.
- Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
- Completion of a training session and demonstrated comprehension of the protocol procedures and knowledge of Shigella associated illness by passing a written examination (70% pass score).
- Availability for the study duration, including all planned follow-up visits.
Key exclusion criteria (8 listed)
- Presence of a significant medical or psychiatric condition that in the opinion of the investigator precludes participation in the study. Some medical conditions that are adequately treated and stable would not preclude entry into the study. These conditions might include stable asthma controlled with inhalers or mild hypertension stably controlled with a single agent.
- Significant abnormalities in screening hematology, or serum chemistry as determined by PI or PI in consultation with the Medical Officer and sponsor.
- Recent of a non-study vaccine or receipt of another investigational product (within 14 days before vaccination).
- Have household contacts who are <3 years old or >70 years old or infirm or immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer chemotherapy, or other chronic debilitating disease).
- Use of any medication that affects the immune function (e.g., corticosteroids and others) within 30 days preceding the first vaccination or planned use during the active study period.
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 |
|---|---|---|
| Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT)2.25 x 10^11 Sf2aWC cells +10 µg dmLT administered orally on Days 0, 28, and 56 | Biological | Cohort 1, Cohort 2, Cohort 3 |
| Shigella flexneri 2a whole cell (Sf2aWC) vaccine2.25 x 10^11 Sf2WC cells administered orally on Days 0, 28, and 56 | Biological | Cohort 1, Cohort 2, Cohort 3 |
| Placebo2.0 grams of NaHCO3 dissolved in 150 mL of sterile water | Other | Cohort 1, Cohort 2, Cohort 3 |
Primary outcome
solicited reactions, AEs, SAEs
Time frame: first vaccination through 6 months post-3rd vaccination
solicited reactions, AEs, SAEs assessed post-vaccination using targeted physical examinations, vital signs, and clinical laboratory tests
prevention of moderate to severe shigellosis
Time frame: up to 24 hours
prevention of moderate to severe shigellosis identified by diarrhea, fever, dysentery, and other signs/symptoms of enteric illness
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2017.
- Individual participant dataSharing planned: No
Related trials for Shigella Sonnei Dysenteries
Active, not recruitingPhase 3
Clinical Trial of the S. Flexneri-S. Sonnei Bivalent Conjugate Vaccine
Dysentery, Dysentery, Shigella
RecruitingPhase 1
Shigella Sonnei 53G Human Infection Study in Kenyan Adults
Shigellosis
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.
Wilbur Chen, MD, MS principal investigator
University of Maryland, Baltimore
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 Shigella flexneri 2a whole cell (Sf2aWC) vaccine and double mutant E. coli heat labile toxin (dmLT) and Shigella flexneri 2a whole cell (Sf2aWC) vaccine in people with Shigella Sonnei Dysenteries, run by PATH 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 5 inclusion and 8 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: withdrawn, as of the sponsor's last update on 20 Nov 2017. 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. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
solicited reactions, AEs, SAEs (time frame: first vaccination through 6 months post-3rd vaccination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Nov 2017.