Vaccine Strain CVD 1208S-122 for Shigellosis

Overseen By Connie Thomas, RN

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Maryland, Baltimore

Must not be taking: Antimicrobials, Steroids, Immunomodulators, others

Disqualifiers: Pregnancy, Breastfeeding, Gastrointestinal illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 7 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and immune response of a new oral vaccine, Strain CVD 1208S-122, for Shigellosis, a bacterial infection that can cause severe diarrhea. Participants will receive either one or two doses of the vaccine or a placebo, a harmless substance resembling the vaccine. The trial suits adults in good health who are not on daily prescription medications and have not experienced recent infections or travel-related gut issues. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I have to stop taking my current medications to join the trial?

Yes, if you have a chronic medical condition that requires daily prescription medication, you would not be eligible to participate. However, if your condition only requires infrequent medication, you may still be eligible if the investigator determines it is safe.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the vaccine strain CVD 1208S-122 is generally safe for people. Studies have found that similar Shigella vaccines are well tolerated by both adults and children, including those with weaker immune systems. In these studies, no serious side effects were reported. The vaccine also has a good safety record, indicating it didn't cause major problems for recipients. Specifically, previous patients demonstrated that CVD 1208S is safe and can trigger an immune response, fulfilling its intended purpose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Shigella vaccine strain CVD 1208S-122 because it takes a novel approach to preventing shigellosis, a disease typically managed with antibiotics. Unlike antibiotics, which can lead to resistance over time, this vaccine aims to provide immunity against the Shigella bacteria by introducing a weakened strain to stimulate the immune system. This method not only reduces the risk of antibiotic resistance but also offers a preventative solution, potentially lowering infection rates and improving public health outcomes. By exploring different dosages and schedules across its cohorts, this vaccine could provide insights into optimal protection against shigellosis.

What evidence suggests that the vaccine strain CVD 1208S-122 could be effective for Shigellosis?

Research has shown that the vaccine strain CVD 1208S-122, which participants in this trial may receive, may help protect against Shigella infections. Studies suggest this vaccine can be up to 60% effective in preventing moderate to severe diarrhea caused by certain Shigella strains included in the vaccine. It has also demonstrated 80% effectiveness against diarrhea caused by all Shigella strains. These findings indicate that the vaccine can trigger a strong immune response. Additionally, both adults and children have tolerated the vaccine well, experiencing no significant side effects. ^{1 3 6 7 8}

Who Is on the Research Team?

Wilbur Chen, MD, MS

Principal Investigator

Center for Vaccine Development and Global Health, University of Maryland School of Medicine

Are You a Good Fit for This Trial?

Healthy adults aged 18-49 who can stay inpatient for up to 6 days, not part of other trials, and women must use birth control. Excludes pregnant or breastfeeding women, those with poor venous access, prior ETEC/Shigella vaccines or infections within 3 years, abnormal bowel habits, recent antimicrobials or steroids use, psychiatric diseases, immunosuppression conditions, certain occupations (food handling/childcare), recent COVID-19 symptoms without a negative test result.

Inclusion Criteria

Written informed consent provided

A passing score (≥70%) on a Comprehension Assessment Tool

For Participants of Cohorts 1-3 during the time when a U.S. Public Health Emergency for COVID-19 exists, SARS-CoV-2 testing must be performed upon admission to the inpatient ward and must document a negative test result prior to vaccination.

Exclusion Criteria

I haven't taken any immune-affecting drugs in the last 30 days.

You have a history of alcohol or drug abuse in the past 5 years.

Poor venous access, as defined by inability to obtain venous blood, for screening labs, after 3 venipuncture attempts

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single oral dose of the study vaccine or placebo in a dose-escalation format, followed by monitoring for safety and immunogenicity

7 days

Inpatient stay for 4 days, followed by outpatient monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse reactions and fecal shedding

28 days

Long-term follow-up

Monitoring for serious adverse events and SUSARs throughout the study period

6-7 months

What Are the Treatments Tested in This Trial?

Interventions

• Strain CVD 1208S-122

Trial Overview The trial is testing the safety and immune response to a live oral vaccine called strain CVD 1208S-122 against Shigella and ETEC infections. Participants will either receive the vaccine candidate or a placebo for comparison.

How Is the Trial Designed?

Group I: Cohort 4: Shigella Vaccine or Placebo Experimental Treatment 2 Interventions

2:2:1 randomization to receive either two doses of vaccine, 1 dose of vaccine and one dose of placebo, or two doses of placebo at Days 1 and 29 (Cohort n=30)

Group II: Cohort 3: Shigella Vaccine at 10^10 cfu or Placebo Experimental Treatment 2 Interventions

3:1 randomization to one dose of vaccine or placebo (Cohort n=8)

Group III: Cohort 2: Shigella Vaccine at 10^9 cfu or Placebo Experimental Treatment 2 Interventions

3:1 randomization to one dose of vaccine or placebo (Cohort n=8)

Group IV: Cohort 1: Shigella Vaccine at 10^8 cfu or Placebo Experimental Treatment 2 Interventions

3:1 randomization to one dose of vaccine or placebo (Cohort n=8)

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3771495/

Clinical trials of Shigella vaccines: two steps forward and one ... These vaccine strains proved to be well tolerated clinically when administered to adults, healthy children and even debilitated institutionalized children, with ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X22015626

Vaccine value profile for Shigella 60% efficacy against MSD caused by Shigella strains in the vaccine, 80% efficacy against MSD caused by all Shigella strains, Bill & Melinda ...

3. mdpi.com mdpi.com/1422-0067/25/8/4329

Shigella Vaccines: The Continuing Unmet Challenge The combined Shigella-ETEC vaccine candidate, CVD 1208S-122, provided further evidence of a Shigella LAV's ability to induce antibody responses and provide ...

4. nature.com nature.com/articles/nrmicro1662

Clinical trials of Shigella vaccines: two steps forward and ... These vaccine strains proved to be well tolerated clinically when administered to adults, healthy children and even debilitated institutionalized children, with ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00866476

Safety and Efficacy Study of CVD 1208S, a Live ... The primary objective of the Phase 2b challenge study is to measure the protective efficacy of 3 spaced doses of vaccine after ingestion of an oral challenge ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X16002863

Status of vaccine research and development for Shigella An effective Shigella vaccine could substantially reduce the global burden of shigellosis and also reduce Shigella-associated mortality and ...

7. tandfonline.com tandfonline.com/doi/pdf/10.4161/hv.4746

Safety and Immunogenicity of CVD 1208S, a Live, Oral < ... We conclude that CVD 1208S retains a favorable safety and immunogenicity profile after reconstruction on animal‑free media, comparable to that ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5851169/

T cell mediated immunity induced by the live-attenuated ... The live-attenuated Shigella flexneri 2a vaccine candidate CVD 1208S (S. flexneri 2a; ΔguaBA, Δset, Δsen) demonstrated to be safe and ...