ShigellaPhase 2NCT04078022
Shigella CVD 30000: Study of Responses to Vaccination With Shigella Vaccine
A Phase 2 study testing SF2a-TT15 Shigella Vaccine and S. flexneri 2a strain 2457T Challenge Agent in people with Shigella, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
The purpose of this study is to determine whether SF2a-TT15 (a monovalent synthetic carbohydrate-based conjugate Shigella vaccine) is safe and effective in the prevention of Shigella infection. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Shigella
- What is being tested?
- SF2a-TT15 Shigella Vaccine and S. flexneri 2a strain 2457T Challenge Agent
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Mar 2020to 25 Jan 2024
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female of age 18-45 years
- Provides written informed consent
- Healthy, based on history, exam, and medications
- Documented acceptable screening laboratory work, including:
- WBC, ANC, Hg, Platelets Creatinine, ALT, Bili Serum IgA HIV, HBsAg, HCV Negative for HLA-B27 (this criterion does not apply to cohort 4) Stool culture urinalysis
- Passing score on Comprehension Assessment Tool (greater than or equal to 70 percent correct answers)
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- Agrees not to participate in another interventional clinical trial during the study period
- For females of child-bearing potential, must agree to acceptable birth control, 4 weeks before enrollment and through 4 weeks after last vaccination or challenge
- Available for a 12-day inpatient stay (this criterion does not apply to cohort 4)
Who cannot join
- Positive pregnancy test at screening or within 24 hours of study product dosing
- Poor venous access, as defined by inability to obtain venous blood after 3 venipuncture attempts (this criterion does not apply to cohort 4)
- Abnormal vital signs, defined as:
- Systolic BP greater than 150 mmHg or Diastolic BP greater than 90 mmHg Resting heart rate greater than 100 Oral temperature greater than or equal to 100.4 degrees F
- Persons with IgA deficiency (serum IgA less than 70 mg per dL
- Serum S. flexneri 2a LPS igG titer greater than or equal to 2500
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- Received prior vaccines or had prior infection (natural or challenge) with ETEC or Shigella, within 5 years prior to enrollment
- Symptoms of Traveler's diarrhea associated with travel to countries where Shigella or other enteric infections are endemic (most of the developing world) within 3 years prior to enrollment
- History of chronic gastrointestinal illness, including sever dyspepsia, lactose intolerance, or other significant gastrointestinal tract disease
- Use of antimicrobials within 2 weeks of each dose of vaccine or the challenge
- Regular use (greater than or equal to weekly) of laxatives, anti-diarrheal agents, anti-constipation agents, or antacid therapies
- History of major gastrointestinal surgery (uncomplicated laparoscopic appendectomy or cholecystectomy greater than 1 year prior is permitted)
- Abnormal bowel pattern, defined by less than 3 stools per week or greater than 2 stools per day in the past 6 months
- Use of oral, parenteral or high-dose inhaled steroids within 30 days of each dose of vaccine or the challenge
- Use of any medication which might affect immune function within 30 days of each dose of vaccine or the challenge
- Current medical condition which requires daily or weekly prescribed medications for control (as medication use is limited during the inpatient stay), may be an exclusion criterion if in the judgement of the investigator the potential for missed doses could represent a significant risk to the subject's health
- History of reactive arthritis
- Diagnosis of schizophrenia or other major psychiatric disease
- History of seizure disorder within the last 5 years
- History of alcohol or drug abuse within the last 5 years
- Presence of immunosuppression
- Known significant allergy (i.e., anaphylaxis) to ciprofloxacin, trimethoprim-sulfamethoxazole (Bactrim), or a tetanus-containing vaccine
- 12-lead electrocardiogram with pathologic abnormalities (this criterion does not apply to cohort 4)
- Occupation in food handling industry, living with, or care of very young children (less than 5 years old), elderly (greater than 65 years), or immunocompromised (this criterion does not apply to cohort 4)
- Having any known legal obligations, court appearances, professional meetings, vacations, planned events, or other reasons which might interfere with a person's availability for a 12-day inpatient stay. (this criterion does no apply to cohort 4)
- Any other criteria which, in the investigator's opinion, would compromise the safety of the study, the ability of a subject to participate, or the results of the study
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland, Baltimore, Center for Vaccine Development and Global Health
Baltimore, Maryland, 21201
About this study
Official title: Phase 2b Study of the Safety, Immunogenicity, and Efficacy of a Monovalent Synthetic Carbohydrate-based Conjugate Vaccine (SF2a-TT15) for Protection Against Shigella Flexneri 2a Experimental Infection
The purpose of this study is to determine whether SF2a-TT15 (a monovalent synthetic carbohydrate-based conjugate Shigella vaccine) is safe and effective in the prevention of Shigella infection.
Read the detailed description
The purpose of this study is to determine whether SF2a-TT15 (a monovalent synthetic carbohydrate-based conjugate Shigella vaccine) is safe and effective in the prevention of Shigella infection. This will be a phase 2b, double-blind, placebo-controlled, single-center study, involving a vaccination phase and a challenge phase. The vaccination phase will consist of study participants that will be 1:1 randomized to receive either the vaccine or placebo. Two doses of blinded study product will be given by intramuscular route of administration, separated by approximately 4 weeks. The challenge phase will consist of an inpatient stay of approximately 12 days during which eligible study participants will ingest an oral inoculum of wild-type S flexneri 2a strain 2457T and then be monitored for illness and treated with antibiotics when the primary endpoint is reached or upon 5 days post-challenge, whichever comes first, or when deemed necessary. Upon satisfying discharge criteria, study participants will complete outpatient clinic follow-up visits through ~7 months after last dose of blinded study product (Day 237). The efficacy study will be enrolled through three cohorts of participants, each cohort consisting of approximately 30 subjects that will be involved in the vaccination phase and 22 subjects that will proceed with the challenge phase. There will be a fourth cohort of participants, consisting of 12 subjects, that will receive the vaccine in an open-label design-this cohort will provide serum samples which are intended to be used for generating serum standards for laboratory assays, as a part of ongoing and future clinical development of Shigella vaccines.
- Conditions
- Shigella
- Being tested
- SF2a-TT15 Shigella Vaccine, Placebo, S. flexneri 2a strain 2457T Challenge Agent
- Medical subject headings
- Dysentery, Bacillary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SF2a-TT15 Shigella VaccineBiological
0.5 mL of the vaccine is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29.
PlaceboOther
0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29.
S. flexneri 2a strain 2457T Challenge AgentBiological
Each participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Shigella Vaccine or Placebo, Followed by Challenge | Experimental | 1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22). Receives: Biological: SF2a-TT15 Shigella Vaccine; Other: Placebo; Biological: S. flexneri 2a strain 2457T Challenge Agent |
| Cohort 2: Shigella Vaccine or Placebo, Followed by Challenge | Experimental | 1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22). Receives: Biological: SF2a-TT15 Shigella Vaccine; Other: Placebo; Biological: S. flexneri 2a strain 2457T Challenge Agent |
| Cohort 3: Shigella Vaccine or Placebo, Followed by Challenge | Experimental | 1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22). Receives: Biological: SF2a-TT15 Shigella Vaccine; Other: Placebo; Biological: S. flexneri 2a strain 2457T Challenge Agent |
| Cohort 4: Shigella Vaccine Only, No Challenge | Experimental | All volunteers receive the investigational Shigella vaccine (n=12). No Shigella challenge. Receives: Biological: SF2a-TT15 Shigella Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Moderate-Severe Shigellosis Illness, With Challenge
Count of participants with primary endpoint (Moderate-Severe Shigellosis)
Measured: 10 days after challenge
Secondary outcomes (5)
Number of Participants Meeting Other Case Definitions and Endpoint Definitions
Measured: 10 days after challenge
Number of Participants With Anti-LPS Serum IgG ELISA Response
Anti-LPS serum IgG ELISA response, by response rates (proportion of 4-fold increases from baseline, Day 1)
Measured: Days 29, 57 and 85
Anti-LPS Serum IgG ELISA Response, by Titer
Measured: Days 1, 29, 57 and 85
Serum Bactericidal Activity Response, by Response Rates (Proportion of 4-fold Increases From Baseline, Day 1)
Measured: Days 29, 57 and 85
Serum Bactericidal Activity Response, by Titer
Measured: Days 1, 29, 57 and 85
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2019
- Study start2 Mar 2020
- Primary completion24 Jan 2023
- Study completion25 Jan 2024
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.
- Other trials for ShigellaStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe sponsor's other registered studies.
- 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
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wilbur Chen, MD, MS, University of Maryland, Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04078022
- Sponsor's protocol ID
- HP-00086278
- Status last verified
- May 2024
- First submitted
- 3 Jul 2019
- Last updated
- 20 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2b Study of the Safety, Immunogenicity, and Efficacy of a Monovalent Synthetic Carbohydrate-based Conjugate Vaccine (SF2a-TT15) for Protection Against Shigella Flexneri 2a Experimental Infection
- ClinicalTrials.gov ID
- NCT04078022
- Acronym / sponsor ID
- HP-00086278
- Conditions
- Shigella
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Study start
- 2 Mar 2020 (actual)
- Primary completion
- 24 Jan 2023 (actual)
- Study completion
- 25 Jan 2024 (actual)
- First posted
- 4 Sep 2019 (actual)
- Results
- Posted 20 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether SF2a-TT15 (a monovalent synthetic carbohydrate-based conjugate Shigella vaccine) is safe and effective in the prevention of Shigella infection.
Detailed description
The purpose of this study is to determine whether SF2a-TT15 (a monovalent synthetic carbohydrate-based conjugate Shigella vaccine) is safe and effective in the prevention of Shigella infection. This will be a phase 2b, double-blind, placebo-controlled, single-center study, involving a vaccination phase and a challenge phase. The vaccination phase will consist of study participants that will be 1:1 randomized to receive either the vaccine or placebo. Two doses of blinded study product will be given by intramuscular route of administration, separated by approximately 4 weeks. The challenge phase will consist of an inpatient stay of approximately 12 days during which eligible study participants will ingest an oral inoculum of wild-type S flexneri 2a strain 2457T and then be monitored for illness and treated with antibiotics when the primary endpoint is reached or upon 5 days post-challenge, whichever comes first, or when deemed necessary. Upon satisfying discharge criteria, study participants will complete outpatient clinic follow-up visits through ~7 months after last dose of blinded study product (Day 237). The efficacy study will be enrolled through three cohorts of participants, each cohort consisting of approximately 30 subjects that will be involved in the vaccination phase and 22 subjects that will proceed with the challenge phase. There will be a fourth cohort of participants, consisting of 12 subjects, that will receive the vaccine in an open-label design-this cohort will provide serum samples which are intended to be used for generating serum standards for laboratory assays, as a part of ongoing and future clinical development of Shigella vaccines.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Shigella Vaccine or Placebo, Followed by Challenge | Experimental | Biological: SF2a-TT15 Shigella Vaccine, Other: Placebo, Biological: S. flexneri 2a strain 2457T Challenge Agent1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22). |
| Cohort 2: Shigella Vaccine or Placebo, Followed by Challenge | Experimental | Biological: SF2a-TT15 Shigella Vaccine, Other: Placebo, Biological: S. flexneri 2a strain 2457T Challenge Agent1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22). |
| Cohort 3: Shigella Vaccine or Placebo, Followed by Challenge | Experimental | Biological: SF2a-TT15 Shigella Vaccine, Other: Placebo, Biological: S. flexneri 2a strain 2457T Challenge Agent1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22). |
| Cohort 4: Shigella Vaccine Only, No Challenge | Experimental | Biological: SF2a-TT15 Shigella VaccineAll volunteers receive the investigational Shigella vaccine (n=12). No Shigella challenge. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Male or female of age 18-45 years
- Provides written informed consent
- Healthy, based on history, exam, and medications
- Documented acceptable screening laboratory work, including:
- WBC, ANC, Hg, Platelets Creatinine, ALT, Bili Serum IgA HIV, HBsAg, HCV Negative for HLA-B27 (this criterion does not apply to cohort 4) Stool culture urinalysis
Key exclusion criteria (26 listed)
- Positive pregnancy test at screening or within 24 hours of study product dosing
- Poor venous access, as defined by inability to obtain venous blood after 3 venipuncture attempts (this criterion does not apply to cohort 4)
- Abnormal vital signs, defined as:
- Systolic BP greater than 150 mmHg or Diastolic BP greater than 90 mmHg Resting heart rate greater than 100 Oral temperature greater than or equal to 100.4 degrees F
- Persons with IgA deficiency (serum IgA less than 70 mg per dL
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 |
|---|---|---|
| SF2a-TT15 Shigella Vaccine0.5 mL of the vaccine is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. | Biological | Cohort 1: Shigella Vaccine or Placebo, Followed by Challenge, Cohort 2: Shigella Vaccine or Placebo, Followed by Challenge, Cohort 3: Shigella Vaccine or Placebo, Followed by Challenge, Cohort 4: Shigella Vaccine Only, No Challenge |
| Placebo0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. | Other | Cohort 1: Shigella Vaccine or Placebo, Followed by Challenge, Cohort 2: Shigella Vaccine or Placebo, Followed by Challenge, Cohort 3: Shigella Vaccine or Placebo, Followed by Challenge |
| S. flexneri 2a strain 2457T Challenge AgentEach participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution. | Biological | Cohort 1: Shigella Vaccine or Placebo, Followed by Challenge, Cohort 2: Shigella Vaccine or Placebo, Followed by Challenge, Cohort 3: Shigella Vaccine or Placebo, Followed by Challenge |
Primary outcome
Number of Participants With Moderate-Severe Shigellosis Illness, With Challenge
Time frame: 10 days after challenge
Count of participants with primary endpoint (Moderate-Severe Shigellosis)
5 secondary outcomes
Number of Participants Meeting Other Case Definitions and Endpoint Definitions
Time frame: 10 days after challenge
Number of Participants With Anti-LPS Serum IgG ELISA Response
Time frame: Days 29, 57 and 85
Anti-LPS Serum IgG ELISA Response, by Titer
Time frame: Days 1, 29, 57 and 85
Serum Bactericidal Activity Response, by Response Rates (Proportion of 4-fold Increases From Baseline, Day 1)
Time frame: Days 29, 57 and 85
Serum Bactericidal Activity Response, by Titer
Time frame: Days 1, 29, 57 and 85
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 SF2a-TT15 Shigella Vaccine and S. flexneri 2a strain 2457T Challenge Agent in people with Shigella, run by University of Maryland, Baltimore 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 9 inclusion and 26 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 20 May 2024. 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?
Yes. Results are posted in the registry (first posted 20 May 2024). 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?
Number of Participants With Moderate-Severe Shigellosis Illness, With Challenge (time frame: 10 days after challenge). 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 May 2024.