ShigellosisPhase 2NCT02646371
Phase 2b Challenge Study With the Bioconjugate Vaccine Flexyn2a
A Phase 2 study testing Flexyn2a in people with Shigellosis, run by LimmaTech Biologics AG at 1 site in United States.
Trial summary
In this proof of concept challenge study, the bioconjugate candidate vaccine Flexyn2a will be tested for its ability to induce an immune response that protects healthy adult volunteers from infection with a wild-type Shigella flexneri 2a strain compared to subjects receiving placebo. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Shigellosis
- What is being tested?
- Flexyn2a
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to Jul 2017
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or female age 18-50 years (inclusive)
- Good health, without clinically significant medical history or physical examination findings.
- Negative serum pregnancy test at screening, and negative urine before each vaccination and before challenge for female subjects of childbearing potential.
- Females of childbearing potential must agree to avoid pregnancy by use of effective contraception. Abstinence is not acceptable as effective contraception. Female subjects unable to bear children must have this documented (e.g. tubal ligation or hysterectomy).
- 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, knowledge of Shigella-associated illness, and a passing score of 70% or better on a written examination.
- Availability for the study duration, including all planned follow-up visits.
- Willingness to refrain from participating in other studies of investigational products until completion of the last study visit.
Who cannot join
- Women currently nursing.
- Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study.
- Clinically significant abnormalities in screening hematology or serum chemistry as determined by PI or PI in consultation with the research monitor and sponsor.
- Presence in the serum of HIV antibody, HBs-Ag, or HCV antibody (if confirmed positive by HepC confirmatory test, i.e. RIBA, PCR)
- Evidence of IgA deficiency (serum IgA < 7 mg/dl or limit of detection of assay).
- Evidence of current excessive alcohol consumption or drug dependence.
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- Evidence of impaired immune function.
- BMI <19 and ≥35
- Recent vaccination or receipt of an investigational product (within 30 days before vaccination and until last study visit).
- Personal history of an inflammatory arthritis.
- Positive blood test for HLA-B27.
- Personal history of irritable bowel syndrome as defined by Rome III criteria.
- Treatment with immunoglobulins or blood products within 3 months from first candidate vaccine injection.
- Regularly abnormal stool pattern (fewer than 3 per week or more than 3 per day) or loose or liquid stools
- Regular use of laxatives, antacids, or other agents to lower stomach acidity.
- Use of any medication known to affect the immune function (e.g., systemic steroids) within 30 days preceding the first vaccination or planned use during the entire study period.
- Known allergy to any of the following antibiotics: ciprofloxacin, trimethoprim-sulfamethoxazole or penicillin.
- Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where Shigella infection is endemic (most of the developing world) within two years prior to dosing, OR planned travel to endemic countries during the length of the study.
- Vaccination for or ingestion of Shigella within 3 years prior to vaccination.
- Use of antibiotics during the 7 days before vaccination and challenge
- Use of proton pump inhibitors, H2 blockers or antacids within 48 hours prior to challenge.
- Serum IgG titer to Shigella flexneri 2a LPS ≥ 2500
- Current occupation involving handling of Shigella bacteria
- History of allergy to any vaccine or to soy
- 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
Johns Hopkins Bloomberg School of Public Health, CIR
Baltimore, Maryland, 21205
About this study
Official title: Phase 2b, Double-blind, Placebo-controlled Efficacy Challenge Study With a Candidate Bioconjugate Vaccine Against Shigella Flexneri 2a
In this proof of concept challenge study, the bioconjugate candidate vaccine Flexyn2a will be tested for its ability to induce an immune response that protects healthy adult volunteers from infection with a wild-type Shigella flexneri 2a strain compared to subjects receiving placebo.
Read the detailed description
Flexyn2a is a bioconjugate candidate vaccine that is able to induce an humoral immune response specific for the 2a-antigen of Shigella flexneri 2a bacteria. Healthy adult volunteers naïve for Shigella flexneri 2a infections at screening will receive two administrations of 10 micrograms Flexyn2a or placebo 4 weeks apart. Four weeks after the second vaccination, each subject will be challenged with 1500 cfu of the virulent Shigella flexneri 2a strain 2457T. In order to assess the ability of Flexyn2a to protect against infection with this strain, the attack rate of shigellosis in the group vaccinated with Flexyn2a will be compared to the group of the subjects who received placebo injections.
- Conditions
- Shigellosis
- Being tested
- Flexyn2a, Placebo
- Medical subject headings
- Dysentery, Bacillary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Flexyn2aBiological
2 doses of 10 μg of Flexyn2a will be injected intramuscularly 4 weeks apart
PlaceboBiological
2 doses of TBS solution will be injected intramuscularly 4 weeks apart
| Study group | Role | What they receive |
|---|---|---|
| Flexyn2a | Active comparator | 2 doses of 10 μg of Flexyn2a will be injected intramuscularly 4 weeks apart Receives: Biological: Flexyn2a |
| Placebo | Placebo comparator | 2 doses of TBS solution will be injected intramuscularly 4 weeks apart Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Attack Rate of Shigellosis in Vaccinated Subjects.
The attack rate of shigellosis after challenge in vaccine group versus in placebo group was analyzed.
Measured: Between Day 56 and Day 64
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2016 (estimated)
- Study startDec 2015
- Primary completionSep 2016
- Study completionJul 2017
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 ShigellosisStudies 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- LimmaTech Biologics AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Johns Hopkins Bloomberg School of Public Health
- Responsible party
- Sponsor
- Investigators
- Kawsar R Talaat, MD, Principal investigator, Johns Hopkins Bloomberg School of Public HealthPatricia Martin, PhD, Study director, LimmaTech Biologics AG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02646371
- Sponsor's protocol ID
- SF2A-2B
- Status last verified
- Jan 2021
- First submitted
- 23 Dec 2015
- Last updated
- 27 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Talaat KR, Alaimo C, Martin P, Bourgeois AL, Dreyer AM, Kaminski RW, Porter CK, Chakraborty S, Clarkson KA, Brubaker J, Elwood D, Frolich R, DeNearing B, Weerts H, Feijoo BL, Halpern J, Sack D, Riddle MS, Fonck VG. Human challenge study with a Shigella bioconjugate vaccine: Analyses of clinical efficacy and correlate of protection. EBioMedicine. 2021 Apr;66:103310. doi: 10.1016/j.ebiom.2021.103310. Epub 2021 Apr 13.
PubMed 33862589
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2b, Double-blind, Placebo-controlled Efficacy Challenge Study With a Candidate Bioconjugate Vaccine Against Shigella Flexneri 2a
- ClinicalTrials.gov ID
- NCT02646371
- Acronym / sponsor ID
- SF2A-2B
- Conditions
- Shigellosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- LimmaTech Biologics AGIndustry (pharma, biotech, devices)
- Collaborators
- Johns Hopkins Bloomberg School of Public Health
- Study start
- Dec 2015 (actual)
- Primary completion
- Sep 2016 (actual)
- Study completion
- Jul 2017 (actual)
- First posted
- 5 Jan 2016 (estimated)
- Results
- Posted 27 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this proof of concept challenge study, the bioconjugate candidate vaccine Flexyn2a will be tested for its ability to induce an immune response that protects healthy adult volunteers from infection with a wild-type Shigella flexneri 2a strain compared to subjects receiving placebo.
Detailed description
Flexyn2a is a bioconjugate candidate vaccine that is able to induce an humoral immune response specific for the 2a-antigen of Shigella flexneri 2a bacteria. Healthy adult volunteers naïve for Shigella flexneri 2a infections at screening will receive two administrations of 10 micrograms Flexyn2a or placebo 4 weeks apart. Four weeks after the second vaccination, each subject will be challenged with 1500 cfu of the virulent Shigella flexneri 2a strain 2457T. In order to assess the ability of Flexyn2a to protect against infection with this strain, the attack rate of shigellosis in the group vaccinated with Flexyn2a will be compared to the group of the subjects who received placebo injections.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Flexyn2a | Active comparator | Biological: Flexyn2a2 doses of 10 μg of Flexyn2a will be injected intramuscularly 4 weeks apart |
| Placebo | Placebo comparator | Biological: Placebo2 doses of TBS solution will be injected intramuscularly 4 weeks apart |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Male or female age 18-50 years (inclusive)
- Good health, without clinically significant medical history or physical examination findings.
- Negative serum pregnancy test at screening, and negative urine before each vaccination and before challenge for female subjects of childbearing potential.
- Females of childbearing potential must agree to avoid pregnancy by use of effective contraception. Abstinence is not acceptable as effective contraception. Female subjects unable to bear children must have this documented (e.g. tubal ligation or hysterectomy).
- Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
Key exclusion criteria (25 listed)
- Women currently nursing.
- Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study.
- Clinically significant abnormalities in screening hematology or serum chemistry as determined by PI or PI in consultation with the research monitor and sponsor.
- Presence in the serum of HIV antibody, HBs-Ag, or HCV antibody (if confirmed positive by HepC confirmatory test, i.e. RIBA, PCR)
- Evidence of IgA deficiency (serum IgA < 7 mg/dl or limit of detection of assay).
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 |
|---|---|---|
| Flexyn2a2 doses of 10 μg of Flexyn2a will be injected intramuscularly 4 weeks apart | Biological | Flexyn2a |
| Placebo2 doses of TBS solution will be injected intramuscularly 4 weeks apart | Biological | Placebo |
Primary outcome
Attack Rate of Shigellosis in Vaccinated Subjects.
Time frame: Between Day 56 and Day 64
The attack rate of shigellosis after challenge in vaccine group versus in placebo group was analyzed.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33862589Talaat KR, Alaimo C, Martin P, Bourgeois AL, Dreyer AM, Kaminski RW, Porter CK, Chakraborty S, Clarkson KA, Brubaker J, Elwood D, Frolich R, DeNearing B, Weerts H, Feijoo BL, Halpern J, Sack D, Riddle MS, Fonck VG. Human challenge study with a Shigella bioconjugate vaccine: Analyses of clinical efficacy and correlate of protection. EBioMedicine. 2021 Apr;66:103310. doi: 10.1016/j.ebiom.2021.103310. Epub 2021 Apr 13.
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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.
Kawsar R Talaat, MD principal investigator
Johns Hopkins Bloomberg School of Public Health
Patricia Martin, PhD study director
LimmaTech Biologics AG
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 Flexyn2a in people with Shigellosis, run by LimmaTech Biologics AG 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 25 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 27 Jan 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 27 Jan 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?
Attack Rate of Shigellosis in Vaccinated Subjects. (time frame: Between Day 56 and Day 64). 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 NCT02646371, 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 27 Jan 2021.