ShigellosisPhase 1NCT01509846
Safety Study of Inactivated Shigella Whole Cell Vaccine in Adults
A Phase 1 study testing Vaccine: 2.6±0.8 x 10^8 vp/mL, 1 dose, Vaccine: 2.6±0.8 x 10^9 vp/mL, 3 doses and Vaccine: 2.6±0.8 x 10^10 vp/mL, 3 doses in people with Shigellosis, run by PATH at 2 sites in United States.
Trial summary
This is a research study about an experimental (investigational) oral inactivated whole cell Shigella flexneri 2a killed vaccine (Sf2aWC). 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
- Shigellosis
- What is being tested?
- Vaccine: 2.6±0.8 x 10^8 vp/mL, 1 dose, Vaccine: 2.6±0.8 x 10^9 vp/mL, 3 doses and Vaccine: 2.6±0.8 x 10^10 vp/mL, 3 doses
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 2 sitesUnited States
- Study dates
- Mar 2011to Dec 2012
- Phase
- Phase 1
- 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
- Healthy adults, male or female, age 18 to 45 years (inclusive) at the time of enrollment.
- Completion and review of comprehension test (achieved >70% accuracy).
- Signed informed consent form.
- Available for the required follow-up period and scheduled clinic visits.
- Negative urine pregnancy test before each vaccination for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is also acceptable.
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, hypertension or depression controlled with medication.
- Clinically significant abnormalities on physical examination.
- Clinically significant abnormalities in screening hematology, serum chemistry, or urinalysis as determined by PI or PI in consultation with Medical Monitor.
- History of febrile illness within 48 hours prior to vaccination.
- BMI <19 or >34.
- Positive blood test for HBsAG, hepatitis C virus (HCV), HIV-1, Human leukocyte antigen (HLA)-B27.
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- Women currently nursing.
- History of reactive arthritis.
- Evidence of current excessive alcohol consumption
- Evidence of current drug use or drug dependence.
- Regular use of anti-diarrheal, anti-constipation, or antacid therapy (excluding use associated with spicy meals).
- Abnormal stool pattern (fewer than 3 stools per week or more than 3 stools per day) on a regular basis; loose or liquid stools on other than an occasional basis.
- Personal or family history of an inflammatory arthritis.
- History of allergy to soy products.
- History of microbiologically confirmed Shigella infection within 3 years.
- Prior receipt of experimental Shigella vaccine or live Shigella challenge within 3 years.
- Symptoms of travelers' 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.
- Occupation involving handling of Shigella bacteria currently, or in the past 3 years.
- History of diarrhea during the 7 days before vaccination.
- Use of antibiotics during the 7 days before vaccination.
- Use of proton pump inhibitors, H2 blockers, or antacids within 48 hours prior to dosing.
- Inability to comply with inpatient rules and regulations.
- Use of immunosuppressive and/or immunomodulative drugs such as corticosteroids or chemotherapeutics that may influence antibody development.
- Participation in research involving another investigational product (defined as receipt of investigational product or exposure to invasive investigational device) 30 days before planned date of first vaccination.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Center for Immunization Research (CIR) at Johns Hopkins School of Public Health (JHSPH)
Baltimore, Maryland, 21224
Johns Hopkins University CIR Isolation Unit
Baltimore, Maryland, 21224
About this study
Official title: A Phase 1 Study to Evaluate the Safety, Tolerability, and Immunogenicity of an Oral Inactivated Whole Cell Shigella Flexneri 2a Vaccine in Healthy Adult Subjects
This is a research study about an experimental (investigational) oral inactivated whole cell Shigella flexneri 2a killed vaccine (Sf2aWC). Sf2aWC is a killed vaccine that is being made to prevent disease from Shigella., which causes bloody, watery diarrhea. Infants and children living in developing countries experience the greatest consequences of this disease. The purpose of this study is to find a dose of the vaccine that is safe, tolerable, and develops an immune response. About 82 healthy adults, ages 18-45, will participate in this study. This study will require volunteers to stay in the research facility for several nights for the first dose. Participants in Cohorts 2, 3, and 4 will not be required to stay overnight for the second and third doses. Participants will be assigned to receive 1 of 4 vaccine doses by mouth. Study procedures include: stool samples, blood samples and documenting side effects. Participants will be involved in study related procedures for about 8 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. If Sf2aWC is safe and immunogenic, it may be combined with S. sonnei and S. flexneri 3a as the basis of a multivalent vaccine, because these three components should cover up to 80% of shigella infections in developing countries and over 90% in developed countries. This is a single site, Phase 1, double-blind, randomized, placebo-controlled, dose-escalation study in healthy adult subjects. Approximately 82 subjects will be enrolled into four separate cohorts and will be randomized to receive Sf2aWC or placebo. The placebo preparation will be bicarbonate buffer. Cohort 1 subjects will receive a single oral dose of Sf2aWC (2.6±0.8 x 10^8 vp/mL) or placebo. Dosing and 72 hours of supervised post-vaccination safety follow-up will be conducted in the Center for Immunization Research, Johns Hopkins School of Public Health (CIR) Inpatient Unit. Before enrolling subjects in subsequent cohorts, safety data from the previous Cohort(s) through Study Day 7 will be evaluated and reviewed by the Safety Review Committee (SRC). Cohorts 2, 3, and 4 participants will receive three doses of Sf2aWC vaccine or placebo at 0, 1 and 2 months. The first immunization will be administered in the CIR inpatient unit, followed by 72 hours of direct post-immunization observation. If after review by the SRC the first dose appears safe and well tolerated, subsequent doses will be administered on an outpatient basis. Safety will be assessed by solicited symptoms/subject memory aid and laboratory evaluations. Adverse events (AE)s will be graded according to standardized criteria. The immunogenicity outcome measures of interest include serum immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies by ELISA against S. flexneri 2a Lipopolysaccharide (LPS) and S. flexneri 2a invasive protein antigens (Ipa), cytokine assays, B and T cell memory responses, and vaccine-specific IgA responses. The proposed sample size of twenty per group in Cohorts 2, 3, and 4 would be sufficient to select the appropriate dose to move into the next study phase, providing that a difference in the immunogenicity between the two arms is 20% or greater. Participants will include 82 healthy adult male and female subjects, ages 18 to 45 inclusive. The primary objective of this study is to assess the safety and tolerability of Sf2aWC vaccine when administered in three oral doses over a range of dose levels in healthy adult subjects. The secondary objective is to assess the immunogenicity of the Sf2aWC vaccine over a range of doses in healthy adult subjects.
- Conditions
- Shigellosis
- Being tested
- Vaccine: 2.6±0.8 x 10^8 vp/mL, 1 dose, Vaccine: 2.6±0.8 x 10^9 vp/mL, 3 doses, Vaccine: 2.6±0.8 x 10^10 vp/mL, 3 doses, Vaccine: 2.6±0.8 x 10^11 vp/mL, 3 doses, Placebo: 1-3 doses
- 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.
Vaccine: 2.6±0.8 x 10^8 vp/mL, 1 doseBiological
Shigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10^8 vp/mL administered on Day 0
Vaccine: 2.6±0.8 x 10^9 vp/mL, 3 dosesBiological
Shigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10^9 vp/mL administered on Days 0, 28, and 56
Vaccine: 2.6±0.8 x 10^10 vp/mL, 3 dosesBiological
Shigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10^10 vp/mL administered on Days 0, 28, and 56
Vaccine: 2.6±0.8 x 10^11 vp/mL, 3 dosesBiological
Shigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10^11 vp/mL administered on Days 0, 28, and 56
Placebo: 1-3 dosesBiological
Placebo administered on Day 0 (if 1 dose) or Day 0, 28, and 56 (3 doses)
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Received one oral dose of 2.6±0.8 x 10^8 vp/mL Shigella flexneri 2a whole cell killed vaccine (Sf2aWC) Receives: Biological: Vaccine: 2.6±0.8 x 10^8 vp/mL, 1 dose |
| Cohort 2 | Experimental | Received three oral doses of 2.6±0.8 x 10^9 vp/mL Shigella flexneri 2a whole cell killed vaccine (Sf2aWC) Receives: Biological: Vaccine: 2.6±0.8 x 10^9 vp/mL, 3 doses |
| Cohort 3 | Experimental | Received three oral doses of 2.6±0.8 x 10^10 vp/mL Shigella flexneri 2a whole cell killed vaccine (Sf2aWC) Receives: Biological: Vaccine: 2.6±0.8 x 10^10 vp/mL, 3 doses |
| Cohort 4 | Experimental | Received three oral doses of 2.6±0.8 x 10^11 vp/mL Shigella flexneri 2a whole cell killed vaccine (Sf2aWC) Receives: Biological: Vaccine: 2.6±0.8 x 10^11 vp/mL, 3 doses |
| Placebo | Placebo comparator | Received oral dose of placebo concurrent with Cohort 1 (one dose), 2, 3, or 4 (3 doses). Receives: Biological: Placebo: 1-3 doses |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Reactogenicity Per Subject and Treatment Group
Local and systemic reactogenicity was assessed post-vaccination using targeted physical examinations, vital signs and clinical laboratory tests, and diary cards (completed following discharge daily through Day 7). Reactogenicity included: nausea, vomiting, fever, abdominal pain, abdominal cramping, bloating, malaise, headache, decreased appetite, generalized myalgias, chills, light-headedness, constipation, excessive flatulence, reactive arthritis, dysentery, loose stool, diarrhea, hypovolemia, joint pain, defecation urgency, and oral temperature.
Measured: 7 days after each vaccination (Day 0, Day 35, Day 63)
Frequency of Unsolicited Adverse Events With a Reasonable Possibility That the Study Product Caused the Event
Measured: 6 months after final vaccination (Day 168 or Day 224)
Secondary outcomes (24)
Number and Percentage of Subjects in Cohort 3 With Positive Immunologic Response in Serum Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response From Baseline
A positive immunological response is defined as an increase of 4-fold or more over the appropriate baseline value for ALS or an increase of more than 2-fold for serological responses (fold increases will be calculated to 1 decimal place). For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14. The fold-change in response was then calculated as the ratio of each value to the baseline value (so the minimum baseline value was 0.14). Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected.
Measured: 35 days
Number and Percentage of Subjects in Cohort 4 With Positive Immunologic Response in Serum Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response From Baseline
A positive immunological response is defined as an increase of 4-fold or more over the appropriate baseline value for ALS or an increase of more than 2-fold for serological responses (fold increases will be calculated to 1 decimal place). For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14. The fold-change in response was then calculated as the ratio of each value to the baseline value (so the minimum baseline value was 0.14). Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected.
Measured: 63 days
Geometric Mean Titer (GMT) of Serum Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response in Cohort 3
- flexneri 2a LPS were used as the ELISA antigens. Immunogenicity responses are presented for Cohorts 3 and 4 only. Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected. For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14.
Measured: 35 days
Geometric Mean Titer (GMT) of Serum Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response in Cohort 4
- flexneri 2a LPS were used as the ELISA antigens. Immunogenicity responses are presented for Cohorts 3 and 4 only. Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected. For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14.
Measured: 63 days
Number and Percentage of Subjects in Cohort 3 With Positive Immunologic Response in Serum Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response From Baseline
A positive immunological response is defined as an increase of 4-fold or more over the appropriate baseline value for ALS or an increase of more than 2-fold for serological responses (fold increases will be calculated to 1 decimal place). For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14. The fold-change in response was then calculated as the ratio of each value to the baseline value (so the minimum baseline value was 0.14). Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected.
Measured: 16 weeks
Number and Percentage of Subjects in Cohort 4 With Positive Immunologic Response in Serum Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response From Baseline
A positive immunological response is defined as an increase of 4-fold or more over the appropriate baseline value for ALS or an increase of more than 2-fold for serological responses (fold increases will be calculated to 1 decimal place). For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14. The fold-change in response was then calculated as the ratio of each value to the baseline value (so the minimum baseline value was 0.14). Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected.
Measured: 16 weeks
Geometric Mean Titer (GMT) of Serum Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response in Cohort 3
- flexneri 2a LPS were used as the ELISA antigens. Immunogenicity responses are presented for Cohorts 3 and 4 only. Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected. For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14.
Measured: 35 days
Geometric Mean Titer (GMT) of Serum Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response in Cohort 4
- flexneri 2a LPS were used as the ELISA antigens. Immunogenicity responses are presented for Cohorts 3 and 4 only. Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected. For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14.
Measured: 16 weeks
Number and Percentage of Subjects With Positive Immunologic Response in Serum Antibody From Lymphocytes Supernatant (ALS) Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response From Baseline
A positive immunological response is defined as an increase of 4-fold or more over the appropriate baseline value for ALS or an increase of more than 2-fold for serological responses (fold increases will be calculated to 1 decimal place). For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14. The fold-change in response was then calculated as the ratio of each value to the baseline value (so the minimum baseline value was 0.14). Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected.
Measured: 63 days
Geometric Mean Titer (GMT) of Serum Antibody From Lymphocytes Supernatant (ALS) Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response From Baseline
- flexneri 2a LPS were used as the ELISA antigens. Immunogenicity responses are presented for Cohorts 3 and 4 only. Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected. For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14.
Measured: 63 days
Number and Percentage of Subjects With Positive Immunologic Response in Serum Antibody From Lymphocytes Supernatant (ALS) Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response From Baseline
A positive immunological response is defined as an increase of 4-fold or more over the appropriate baseline value for ALS or an increase of more than 2-fold for serological responses (fold increases will be calculated to 1 decimal place). For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14. The fold-change in response was then calculated as the ratio of each value to the baseline value (so the minimum baseline value was 0.14). Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected.
Measured: 63 days
Geometric Mean Titer (GMT) of Serum Antibody From Lymphocytes Supernatant (ALS) Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response
- flexneri 2a LPS were used as the ELISA antigens. Immunogenicity responses are presented for Cohorts 3 and 4 only. Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected. For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14.
Measured: 63 days
Number and Percentage of Subjects With Positive Immunologic Response in Invasion Plasmid Antigens B (IpaB) Lymphocytes Supernatant (ALS) Immunoglobulin A (IgA) Response From Baseline
A positive immunological response is defined as an increase of 4-fold or more over the appropriate baseline value for ALS or an increase of more than 2-fold for serological responses (fold increases will be calculated to 1 decimal place). For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14. The fold-change in response was then calculated as the ratio of each value to the baseline value (so the minimum baseline value was 0.14). Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected.
Measured: 63 days
Geometric Mean Titer (GMT) of Invasion Plasmid Antigens B (IpaB) Lymphocytes Supernatant (ALS) Immunoglobulin A (IgA) Response
Whole blood samples were collected for determination of ALS (antibody from lymphocytes supernatant). Immunogenicity responses are presented for Cohorts 3 and 4 only. Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected. For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14.
Measured: 63 days
Number and Percentage of Subjects With Positive Immunologic Response in Invasion Plasmid Antigen D (IpaD) Lymphocytes Supernatant (ALS) Immunoglobulin A (IgA) Response From Baseline
A positive immunological response is defined as an increase of 4-fold or more over the appropriate baseline value for ALS or an increase of more than 2-fold for serological responses (fold increases will be calculated to 1 decimal place). For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14. The fold-change in response was then calculated as the ratio of each value to the baseline value (so the minimum baseline value was 0.14). Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected.
Measured: 63 days
Geometric Mean Titer (GMT) of Invasion Plasmid Antigen D (IpaD) Lymphocytes Supernatant (ALS) Immunoglobulin A (IgA) Response
Whole blood samples were collected for determination of ALS (antibody from lymphocytes supernatant). Immunogenicity responses are presented for Cohorts 3 and 4 only. Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected. For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14.
Measured: 63 days
Number and Percentage of Subjects in Cohort 3 With Positive Immunologic Response in Fecal Immunoglobulin A (IgA) Response From Baseline
A positive immunological response is defined as an increase of 4-fold or more over the appropriate baseline value for ALS or an increase of more than 2-fold for serological responses (fold increases will be calculated to 1 decimal place). For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14. The fold-change in response was then calculated as the ratio of each value to the baseline value (so the minimum baseline value was 0.14). Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected.
Measured: 16 weeks
Geometric Mean Titer (GMT) of Fecal Immunoglobulin A (IgA) Response in Cohort 3
Immunogenicity responses are presented for Cohorts 3 and 4 only. Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected. For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14.
Measured: 16 weeks
Number and Percentage of Subjects in Cohort 3 With Positive Immunologic Response in Total Immunoglobulin A (IgA) Response From Baseline
A positive immunological response is defined as an increase of 4-fold or more over the appropriate baseline value for ALS or an increase of more than 2-fold for serological responses (fold increases will be calculated to 1 decimal place). For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14. The fold-change in response was then calculated as the ratio of each value to the baseline value (so the minimum baseline value was 0.14). Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected.
Measured: 16 weeks
Geometric Mean Titer (GMT) of Total Immunoglobulin A (IgA) Response in Cohort 3
Whole blood samples were collected for determination of ALS (antibody from lymphocytes supernatant). Immunogenicity responses are presented for Cohorts 3 and 4 only. Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected. For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14.
Measured: 16 weeks
Number and Percentage of Subjects in Cohort 4 With Positive Immunologic Response in Total Immunoglobulin A (IgA) Response From Baseline
A positive immunological response is defined as an increase of 4-fold or more over the appropriate baseline value for ALS or an increase of more than 2-fold for serological responses (fold increases will be calculated to 1 decimal place). For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14. The fold-change in response was then calculated as the ratio of each value to the baseline value (so the minimum baseline value was 0.14). Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected.
Measured: 63 days
Geometric Mean Titer (GMT) of Total Immunoglobulin A (IgA) Response in Cohort 4
Whole blood samples were collected for determination of ALS (antibody from lymphocytes supernatant). Immunogenicity responses are presented for Cohorts 3 and 4 only. Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected. For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14.
Measured: 63 days
Number and Percentage of Subjects in Cohort 4 With Positive Immunologic Response in Fecal Immunoglobulin A (IgA) Response From Baseline
A positive immunological response is defined as an increase of 4-fold or more over the appropriate baseline value for ALS or an increase of more than 2-fold for serological responses (fold increases will be calculated to 1 decimal place). For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14. The fold-change in response was then calculated as the ratio of each value to the baseline value (so the minimum baseline value was 0.14). Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected.
Measured: 63 days
Geometric Mean Titer (GMT) of Fecal Immunoglobulin A (IgA) Response in Cohort 4
Immunogenicity responses are presented for Cohorts 3 and 4 only. Specimens from vaccine recipients in Cohorts 1 and 2 were not tested for immunogenicity data and no data were collected. For all immunology variables, the raw values were first adjusted to the geometric mean of positive controls, and any values <0.15 were changed to 0.14.
Measured: 63 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2012 (estimated)
- Study startMar 2011
- Primary completionDec 2012
- Study completionDec 2012
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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- PATH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Clayton D Harro, MD, ScM, Principal investigator, Johns Hopkins Bloomberg School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01509846
- Sponsor's protocol ID
- VAC 001
- Status last verified
- Jul 2021
- First submitted
- 5 Jan 2012
- Last updated
- 11 Aug 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Chakraborty S, Harro C, DeNearing B, Bream J, Bauers N, Dally L, Flores J, Van de Verg L, Sack DA, Walker R. Evaluation of the Safety, Tolerability, and Immunogenicity of an Oral, Inactivated Whole-Cell Shigella flexneri 2a Vaccine in Healthy Adult Subjects. Clin Vaccine Immunol. 2016 Apr 4;23(4):315-25. doi: 10.1128/CVI.00608-15. Print 2016 Apr.
PubMed 26865592
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study to Evaluate the Safety, Tolerability, and Immunogenicity of an Oral Inactivated Whole Cell Shigella Flexneri 2a Vaccine in Healthy Adult Subjects
- ClinicalTrials.gov ID
- NCT01509846
- Acronym / sponsor ID
- VAC 001
- Conditions
- Shigellosis
- Keywords
- Shigella, vaccine, shigellosis, dysentery, whole cell
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- PATHUniversity, hospital or other
- Study start
- Mar 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 13 Jan 2012 (estimated)
- Results
- Posted 11 Aug 2021
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). Sf2aWC is a killed vaccine that is being made to prevent disease from Shigella., which causes bloody, watery diarrhea. Infants and children living in developing countries experience the greatest consequences of this disease. The purpose of this study is to find a dose of the vaccine that is safe, tolerable, and develops an immune response. About 82 healthy adults, ages 18-45, will participate in this study. This study will require volunteers to stay in the research facility for several nights for the first dose. Participants in Cohorts 2, 3, and 4 will not be required to stay overnight for the second and third doses. Participants will be assigned to receive 1 of 4 vaccine doses by mouth. Study procedures include: stool samples, blood samples and documenting side effects. Participants will be involved in study related procedures for about 8 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. If Sf2aWC is safe and immunogenic, it may be combined with S. sonnei and S. flexneri 3a as the basis of a multivalent vaccine, because these three components should cover up to 80% of shigella infections in developing countries and over 90% in developed countries. This is a single site, Phase 1, double-blind, randomized, placebo-controlled, dose-escalation study in healthy adult subjects. Approximately 82 subjects will be enrolled into four separate cohorts and will be randomized to receive Sf2aWC or placebo. The placebo preparation will be bicarbonate buffer. Cohort 1 subjects will receive a single oral dose of Sf2aWC (2.6±0.8 x 10^8 vp/mL) or placebo. Dosing and 72 hours of supervised post-vaccination safety follow-up will be conducted in the Center for Immunization Research, Johns Hopkins School of Public Health (CIR) Inpatient Unit. Before enrolling subjects in subsequent cohorts, safety data from the previous Cohort(s) through Study Day 7 will be evaluated and reviewed by the Safety Review Committee (SRC). Cohorts 2, 3, and 4 participants will receive three doses of Sf2aWC vaccine or placebo at 0, 1 and 2 months. The first immunization will be administered in the CIR inpatient unit, followed by 72 hours of direct post-immunization observation. If after review by the SRC the first dose appears safe and well tolerated, subsequent doses will be administered on an outpatient basis. Safety will be assessed by solicited symptoms/subject memory aid and laboratory evaluations. Adverse events (AE)s will be graded according to standardized criteria. The immunogenicity outcome measures of interest include serum immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies by ELISA against S. flexneri 2a Lipopolysaccharide (LPS) and S. flexneri 2a invasive protein antigens (Ipa), cytokine assays, B and T cell memory responses, and vaccine-specific IgA responses. The proposed sample size of twenty per group in Cohorts 2, 3, and 4 would be sufficient to select the appropriate dose to move into the next study phase, providing that a difference in the immunogenicity between the two arms is 20% or greater. Participants will include 82 healthy adult male and female subjects, ages 18 to 45 inclusive. The primary objective of this study is to assess the safety and tolerability of Sf2aWC vaccine when administered in three oral doses over a range of dose levels in healthy adult subjects. The secondary objective is to assess the immunogenicity of the Sf2aWC vaccine over a range of doses in healthy adult subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Biological: Vaccine: 2.6±0.8 x 10^8 vp/mL, 1 doseReceived one oral dose of 2.6±0.8 x 10^8 vp/mL Shigella flexneri 2a whole cell killed vaccine (Sf2aWC) |
| Cohort 2 | Experimental | Biological: Vaccine: 2.6±0.8 x 10^9 vp/mL, 3 dosesReceived three oral doses of 2.6±0.8 x 10^9 vp/mL Shigella flexneri 2a whole cell killed vaccine (Sf2aWC) |
| Cohort 3 | Experimental | Biological: Vaccine: 2.6±0.8 x 10^10 vp/mL, 3 dosesReceived three oral doses of 2.6±0.8 x 10^10 vp/mL Shigella flexneri 2a whole cell killed vaccine (Sf2aWC) |
| Cohort 4 | Experimental | Biological: Vaccine: 2.6±0.8 x 10^11 vp/mL, 3 dosesReceived three oral doses of 2.6±0.8 x 10^11 vp/mL Shigella flexneri 2a whole cell killed vaccine (Sf2aWC) |
| Placebo | Placebo comparator | Biological: Placebo: 1-3 dosesReceived oral dose of placebo concurrent with Cohort 1 (one dose), 2, 3, or 4 (3 doses). |
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.
- Completion and review of comprehension test (achieved >70% accuracy).
- Signed informed consent form.
- Available for the required follow-up period and scheduled clinic visits.
- Negative urine pregnancy test before each vaccination for female subjects of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is also acceptable.
Key exclusion criteria (24 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, hypertension or depression controlled with medication.
- Clinically significant abnormalities on physical examination.
- Clinically significant abnormalities in screening hematology, serum chemistry, or urinalysis as determined by PI or PI in consultation with Medical Monitor.
- History of febrile illness within 48 hours prior to vaccination.
- BMI <19 or >34.
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 |
|---|---|---|
| Vaccine: 2.6±0.8 x 10^8 vp/mL, 1 doseShigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10^8 vp/mL administered on Day 0 | Biological | Cohort 1 |
| Vaccine: 2.6±0.8 x 10^9 vp/mL, 3 dosesShigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10^9 vp/mL administered on Days 0, 28, and 56 | Biological | Cohort 2 |
| Vaccine: 2.6±0.8 x 10^10 vp/mL, 3 dosesShigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10^10 vp/mL administered on Days 0, 28, and 56 | Biological | Cohort 3 |
| Vaccine: 2.6±0.8 x 10^11 vp/mL, 3 dosesShigella flexneri 2a whole cell killed vaccine (Sf2aWC): 2.6±0.8 x 10^11 vp/mL administered on Days 0, 28, and 56 | Biological | Cohort 4 |
| Placebo: 1-3 dosesPlacebo administered on Day 0 (if 1 dose) or Day 0, 28, and 56 (3 doses) | Biological | Placebo |
Primary outcome
Maximum Reactogenicity Per Subject and Treatment Group
Time frame: 7 days after each vaccination (Day 0, Day 35, Day 63)
Local and systemic reactogenicity was assessed post-vaccination using targeted physical examinations, vital signs and clinical laboratory tests, and diary cards (completed following discharge daily through Day 7). Reactogenicity included: nausea, vomiting, fever, abdominal pain, abdominal cramping, bloating, malaise, headache, decreased appetite, generalized myalgias, chills, light-headedness, constipation, excessive flatulence, reactive arthritis, dysentery, loose stool, diarrhea, hypovolemia, joint pain, defecation urgency, and oral temperature.
Frequency of Unsolicited Adverse Events With a Reasonable Possibility That the Study Product Caused the Event
Time frame: 6 months after final vaccination (Day 168 or Day 224)
24 secondary outcomes
Number and Percentage of Subjects in Cohort 3 With Positive Immunologic Response in Serum Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response From Baseline
Time frame: 35 days
Number and Percentage of Subjects in Cohort 4 With Positive Immunologic Response in Serum Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response From Baseline
Time frame: 63 days
Geometric Mean Titer (GMT) of Serum Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response in Cohort 3
Time frame: 35 days
Geometric Mean Titer (GMT) of Serum Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response in Cohort 4
Time frame: 63 days
Number and Percentage of Subjects in Cohort 3 With Positive Immunologic Response in Serum Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response From Baseline
Time frame: 16 weeks
Number and Percentage of Subjects in Cohort 4 With Positive Immunologic Response in Serum Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response From Baseline
Time frame: 16 weeks
Geometric Mean Titer (GMT) of Serum Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response in Cohort 3
Time frame: 35 days
Geometric Mean Titer (GMT) of Serum Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response in Cohort 4
Time frame: 16 weeks
Number and Percentage of Subjects With Positive Immunologic Response in Serum Antibody From Lymphocytes Supernatant (ALS) Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response From Baseline
Time frame: 63 days
Geometric Mean Titer (GMT) of Serum Antibody From Lymphocytes Supernatant (ALS) Lipopolysaccharide (LPS) Immunoglobulin A (IgA) Response From Baseline
Time frame: 63 days
Number and Percentage of Subjects With Positive Immunologic Response in Serum Antibody From Lymphocytes Supernatant (ALS) Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response From Baseline
Time frame: 63 days
Geometric Mean Titer (GMT) of Serum Antibody From Lymphocytes Supernatant (ALS) Lipopolysaccharide (LPS) Immunoglobulin G (IgG) Response
Time frame: 63 days
Number and Percentage of Subjects With Positive Immunologic Response in Invasion Plasmid Antigens B (IpaB) Lymphocytes Supernatant (ALS) Immunoglobulin A (IgA) Response From Baseline
Time frame: 63 days
Geometric Mean Titer (GMT) of Invasion Plasmid Antigens B (IpaB) Lymphocytes Supernatant (ALS) Immunoglobulin A (IgA) Response
Time frame: 63 days
Number and Percentage of Subjects With Positive Immunologic Response in Invasion Plasmid Antigen D (IpaD) Lymphocytes Supernatant (ALS) Immunoglobulin A (IgA) Response From Baseline
Time frame: 63 days
Geometric Mean Titer (GMT) of Invasion Plasmid Antigen D (IpaD) Lymphocytes Supernatant (ALS) Immunoglobulin A (IgA) Response
Time frame: 63 days
Number and Percentage of Subjects in Cohort 3 With Positive Immunologic Response in Fecal Immunoglobulin A (IgA) Response From Baseline
Time frame: 16 weeks
Geometric Mean Titer (GMT) of Fecal Immunoglobulin A (IgA) Response in Cohort 3
Time frame: 16 weeks
Number and Percentage of Subjects in Cohort 3 With Positive Immunologic Response in Total Immunoglobulin A (IgA) Response From Baseline
Time frame: 16 weeks
Geometric Mean Titer (GMT) of Total Immunoglobulin A (IgA) Response in Cohort 3
Time frame: 16 weeks
Number and Percentage of Subjects in Cohort 4 With Positive Immunologic Response in Total Immunoglobulin A (IgA) Response From Baseline
Time frame: 63 days
Geometric Mean Titer (GMT) of Total Immunoglobulin A (IgA) Response in Cohort 4
Time frame: 63 days
Number and Percentage of Subjects in Cohort 4 With Positive Immunologic Response in Fecal Immunoglobulin A (IgA) Response From Baseline
Time frame: 63 days
Geometric Mean Titer (GMT) of Fecal Immunoglobulin A (IgA) Response in Cohort 4
Time frame: 63 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26865592Chakraborty S, Harro C, DeNearing B, Bream J, Bauers N, Dally L, Flores J, Van de Verg L, Sack DA, Walker R. Evaluation of the Safety, Tolerability, and Immunogenicity of an Oral, Inactivated Whole-Cell Shigella flexneri 2a Vaccine in Healthy Adult Subjects. Clin Vaccine Immunol. 2016 Apr 4;23(4):315-25. doi: 10.1128/CVI.00608-15. Print 2016 Apr.
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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.
Clayton D Harro, MD, ScM principal investigator
Johns Hopkins Bloomberg School of Public Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vaccine: 2.6±0.8 x 10^8 vp/mL, 1 dose, Vaccine: 2.6±0.8 x 10^9 vp/mL, 3 doses and Vaccine: 2.6±0.8 x 10^10 vp/mL, 3 doses in people with Shigellosis, run by PATH at 2 sites 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 24 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 11 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 11 Aug 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?
Maximum Reactogenicity Per Subject and Treatment Group (time frame: 7 days after each vaccination (Day 0, Day 35, Day 63)). 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?
On the ClinicalTrials.gov record for NCT01509846, 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 11 Aug 2021.