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| Name | Class |
|---|---|
| International Centre for Diarrhoeal Disease Research, Bangladesh | OTHER |
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This is a research study of an experimental (investigational) live attenuated Shigella sonnei vaccine (WRSS1) to find a dose of the vaccine that is safe, tolerable, and develops an immune response. Shigella causes bloody and watery diarrhea, and infants and children living in developing countries experience the greatest consequences of this disease.
The WRSS1 vaccine in will be given to healthy toddlers (12-24 months old). The first vaccination was given to toddlers in the inpatient unit and the second and third doses will be administered on an outpatient basis. A safety evaluation was performed after the first dose before enrolling subjects in subsequent cohorts to receive a higher vaccine dose.
After the study was initiated, its funder, the Bill and Melinda Gates Foundation (BMGF) made significant changes to the PATH Enteric Vaccine Initiative (EVI) portfolio and decided not to support the three higher-dose cohorts (Cohort 1, 2, and 3) planned as part of this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: WRSS1 3 x 10³ CFU | Experimental | Healthy toddlers receiving 3 oral doses of 3 x 10³ colony-forming units (CFU) of Shigella sonnei Strain WRSS1 approximately 4 weeks apart. |
|
| Cohort 2: WRSS1 3 x 10⁴ CFU | Experimental | Healthy toddlers receiving 3 oral doses of 3 x 10⁴ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart. |
|
| Cohort 3: WRSS1 3 x 10⁵ CFU | Experimental | Healthy toddlers receiving 3 oral doses of 3 x 10⁵ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart. |
|
| Cohort 4: WRSS1 3 x 10⁶ CFU | Experimental | Healthy toddlers receiving 3 oral doses of 3 x 10⁶ CFU of Shigella sonnei Strain WRSS1 approximately 4 weeks apart. |
|
| Cohort 1: Placebo | Placebo Comparator | Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10³ WRSS1 approximately 4 weeks apart. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Shigella sonnei Strain WRSS1 Vaccine | Biological | Live attenuated, oral Shigella WRSS1 vaccine |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Severity of Reactogenicity by Vaccination | All toddlers were monitored for evidence of immediate reactions, assessed for systemic reactogenicity (fever, irritability, decreased appetite, and decreased activity) and gastrointestinal (GI) symptoms (abdominal pain, nausea, vomiting, loose stool, diarrhea, dysentery, bloating, excess flatulence, constipation) during the 72 hours following each vaccine dose. | 72 hours after each vaccination (Day 3, Day 31, Day 59) |
| Number of Participants With Adverse Events Occurring Within 28 Days After Any Vaccination by Maximum Severity | All toddlers were monitored for the occurrence of any adverse event (AE) or serious adverse event (SAE). Toddlers visited the clinic for safety assessments approximately one month after each vaccination. Grades are based on maximum severity per participant. | Up to 28 days after any vaccination (up to Day 84) |
| Measure | Description | Time Frame |
|---|---|---|
| Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens | The mucosal immune response to WRSS1 was evaluated by assessing specific IgA antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgA response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rubhana Raqib, MD | International Centre for Diarrhoeal Disease Research, Bangladesh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mirpur Field Office | Mirpur | Bangladesh |
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This was a single-site study conducted in Bangladesh. The study originally planned to enroll up to 64 toddlers to receive three doses of 3x10^3, 3x10^4, 3x10^5 or 3x10^6 colony-forming units (CFU) live attenuated, oral shigella WRSS1 vaccine or placebo, however enrollment was terminated after the first dose cohort was enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: WRSS1 3x10³ CFU | Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart. |
| FG001 | Cohort 1: Placebo | Healthy toddlers received 3 oral doses of placebo to WRSS1 approximately 4 weeks apart. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Received Vaccination 1 |
| |||||||||||||
| Received Vaccination 2 |
| |||||||||||||
| Received Vaccination 3 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: WRSS1 | Healthy toddlers received 3 oral doses of 3x10³ CFU Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart. |
| BG001 | Cohort 1: Placebo | Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Severity of Reactogenicity by Vaccination | All toddlers were monitored for evidence of immediate reactions, assessed for systemic reactogenicity (fever, irritability, decreased appetite, and decreased activity) and gastrointestinal (GI) symptoms (abdominal pain, nausea, vomiting, loose stool, diarrhea, dysentery, bloating, excess flatulence, constipation) during the 72 hours following each vaccine dose. | Posted | Count of Participants | Participants | 72 hours after each vaccination (Day 3, Day 31, Day 59) |
|
Serious adverse events were collected through Day 224. Non-serious adverse events are reported through 28 days after any vaccination (up to Day 84).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: WRSS1 | Healthy toddlers received 3 oral doses of 3x10³ colony-forming unit (CFU) Shigella sonnei strain WRSS1 vaccine approximately 4 weeks apart. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sudden death | General disorders | MedDRA (Unspecified) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jorge Flores | PATH | (202) 822-0033 | jeflores@path.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 10, 2017 | Jul 11, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 4, 2018 | Oct 10, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003967 | Diarrhea |
| D004405 | Dysentery, Bacillary |
| D004756 | Enterobacteriaceae Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001423 | Bacterial Infections and Mycoses |
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| Cohort 2: Placebo | Placebo Comparator | Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁴ WRSS1 approximately 4 weeks apart. |
|
| Cohort 3: Placebo | Placebo Comparator | Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁵ WRSS1 approximately 4 weeks apart. |
|
| Cohort 4: Placebo | Placebo Comparator | Healthy toddlers receiving 3 oral doses of placebo to match 3 x 10⁶ WRSS1 approximately 4 weeks apart. |
|
| Placebo | Biological | Sterile saline solution |
|
| Days 0, 7, 35, and 63 |
| Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | The mucosal immune response to WRSS1 was evaluated by assessing specific IgA antibody responses to S. sonnei lipopolysaccharide (LPS) using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants from cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgA response from circulating lymphocytes. | Days 0, 7, 35, and 63 |
| Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | The mucosal immune response to WRSS1 was evaluated by assessing specific IgG antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgG response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC. | Days 0, 7, 35, and 63 |
| Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) | The mucosal immune response to WRSS1 was evaluated by assessing specific IgG antibody responses to S. sonnei LPS using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgG response from circulating lymphocytes. | Days 0, 7, 35, and 63 |
| Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | The mucosal immune response to WRSS1 was evaluated by assessing specific IgM antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgM response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC. | Days 0, 7, 35, and 63 |
| Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | The mucosal immune response to WRSS1 was evaluated by assessing specific IgM antibody responses to S. sonnei LPS using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgM response from circulating lymphocytes. | Days 0, 7, 35, and 63 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
| Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | Days 7, 35, and 63 |
| Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | Days 7, 35, and 63 |
| Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | Days 7, 35, and 63 |
| Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | Days 7, 35, and 63 |
| Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | Days 7, 35, and 63 |
| Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | Days 7, 35, and 63 |
| Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens | The systemic immune response to WRSS1 was evaluated by assessing the IgA antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the enzyme-linked immunosorbent assay (ELISA) plates. | Days 0, 7, 35, and 63 |
| Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen | The systemic immune response to WRSS1 was evaluated by assessing the IgA antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific lipopolysaccharide (LPS) from the Walter Reed Army Institute was used to coat the ELISA plates. | Days 0, 7, 35, and 63 |
| Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen | The systemic immune response to WRSS1 was evaluated by assessing the IgG antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. | Days 0, 7, 35, and 63 |
| Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) | The systemic immune response to WRSS1 was evaluated by assessing the IgG antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. | Days 0, 7, 35, and 63 |
| Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Invaplex Antigen | The systemic immune response to WRSS1 was evaluated by assessing the IgM antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. | Days 0, 7, 35, and 63 |
| Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen | The systemic immune response to WRSS1 was evaluated by assessing the IgM antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. | Days 0, 7, 35, and 63 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum : Invaplex Antigen | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
| Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Invaplex Antigen | Days 7, 35, and 63 |
| Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Invaplex Antigen | Days 7, 35, and 63 |
| Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Invaplex Antigen | Days 7, 35, and 63 |
| Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen | Days 7, 35, and 63 |
| Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen | Days 7, 35, and 63 |
| Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen | Days 7, 35, and 63 |
| Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen | The mucosal immune response to the WRSS1 was evaluated by assessing fecal IgA antibody responses to S. sonnei Invaplex in ELISA assays at Days 0, 7, 28, 35, 56, 63, and 84. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. | Days 0, 7, 28, 35, 56, 63, and 84 |
| Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen | The mucosal immune response to the WRSS1 was evaluated by assessing fecal IgA antibody responses to S. sonnei LPS in ELISA assays at Days 0, 7, 28, 35, 56, 63, and 84. | Days 0, 7, 28, 35, 56, 63, and 84 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigens | Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84 |
| Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen | Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84 |
| Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen | Days 7, 28, 35, 56, 63, and 84 |
| Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen | Days 7, 28, 35, 56, 63, and 84 |
| NOT COMPLETED |
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| NOT COMPLETED |
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| BG002 | Total | Total of all reporting groups |
| months |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Height | Mean | Standard Deviation | cm |
|
| Weight | Mean | Standard Deviation | kilograms |
|
Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart.
|
|
| Primary | Number of Participants With Adverse Events Occurring Within 28 Days After Any Vaccination by Maximum Severity | All toddlers were monitored for the occurrence of any adverse event (AE) or serious adverse event (SAE). Toddlers visited the clinic for safety assessments approximately one month after each vaccination. Grades are based on maximum severity per participant. | Safety population | Posted | Count of Participants | Participants | Up to 28 days after any vaccination (up to Day 84) |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens | The mucosal immune response to WRSS1 was evaluated by assessing specific IgA antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgA response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | The mucosal immune response to WRSS1 was evaluated by assessing specific IgA antibody responses to S. sonnei lipopolysaccharide (LPS) using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants from cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgA response from circulating lymphocytes. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | The mucosal immune response to WRSS1 was evaluated by assessing specific IgG antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgG response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) | The mucosal immune response to WRSS1 was evaluated by assessing specific IgG antibody responses to S. sonnei LPS using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgG response from circulating lymphocytes. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | The mucosal immune response to WRSS1 was evaluated by assessing specific IgM antibody responses to S. sonnei Invaplex using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine Invaplex-specific IgM response from circulating lymphocytes. Invaplex is a mixture of purified S. sonnei lipopolysaccharide (LPS) and purified protein antigens IpaB and IpaC. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | The mucosal immune response to WRSS1 was evaluated by assessing specific IgM antibody responses to S. sonnei LPS using the 'antibodies in lymphocyte supernatant' (ALS) assay on culture supernatants of cultured peripheral blood mononuclear cells from different study days (Days 0, 7, 35, and 63) to determine LPS-specific IgM response from circulating lymphocytes. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 35, and 63 |
|
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| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigens | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
|
|
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| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
|
|
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| Secondary | Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 35, and 63 |
|
|
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| Secondary | Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 35, and 63 |
|
|
|
| Secondary | Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Invaplex Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 35, and 63 |
|
|
|
| Secondary | Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 35, and 63 |
|
|
|
| Secondary | Count of Participants With 4-fold Rise From Baseline in Immunoglobulin G (IgG) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 35, and 63 |
|
|
|
| Secondary | Count of Participants With 4-fold Rise From Baseline in Immunoglobulin M (IgM) Antibodies in Antibody Lymphocyte Supernatant (ALS): Lipopolysaccharide (LPS) Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens | The systemic immune response to WRSS1 was evaluated by assessing the IgA antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the enzyme-linked immunosorbent assay (ELISA) plates. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen | The systemic immune response to WRSS1 was evaluated by assessing the IgA antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific lipopolysaccharide (LPS) from the Walter Reed Army Institute was used to coat the ELISA plates. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen | The systemic immune response to WRSS1 was evaluated by assessing the IgG antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) | The systemic immune response to WRSS1 was evaluated by assessing the IgG antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Invaplex Antigen | The systemic immune response to WRSS1 was evaluated by assessing the IgM antibody response to S. sonnei Invaplex in serum/plasma samples at Days 0, 7, 35 and 63. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen | The systemic immune response to WRSS1 was evaluated by assessing the IgM antibody response to S. sonnei 2a LPS in serum/plasma samples at Days 0, 7, 35 and 63. Serotype-specific LPS from the Walter Reed Army Institute was used to coat the ELISA plates. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Invaplex Antigens | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Invaplex Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin G (IgG) Antibodies in Serum: Lipopolysaccharide (LPS) | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum : Invaplex Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin M (IgM) Antibodies in Serum: Lipopolysaccharide (LPS) Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 35, and 63 |
|
|
|
| Secondary | Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Invaplex Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 35, and 63 |
|
|
|
| Secondary | Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Invaplex Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 35, and 63 |
|
|
|
| Secondary | Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Invaplex Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 35, and 63 |
|
|
|
| Secondary | Count of Participants With 4-fold Rise in Immunoglobulin A (IgA) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 35, and 63 |
|
|
|
| Secondary | Count of Participants With 4-fold Rise in Immunoglobulin G (IgG) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 35, and 63 |
|
|
|
| Secondary | Count of Participants With 4-fold Rise in Immunoglobulin M (IgM) Antibodies in Serum From Baseline: Lipopolysaccharide (LPS) Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 35, and 63 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen | The mucosal immune response to the WRSS1 was evaluated by assessing fecal IgA antibody responses to S. sonnei Invaplex in ELISA assays at Days 0, 7, 28, 35, 56, 63, and 84. Invaplex is a mixture of purified S. sonnei LPS and purified protein antigens IpaB and IpaC. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 28, 35, 56, 63, and 84 |
|
|
|
| Secondary | Geometric Mean Titer (GMT) of Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen | The mucosal immune response to the WRSS1 was evaluated by assessing fecal IgA antibody responses to S. sonnei LPS in ELISA assays at Days 0, 7, 28, 35, 56, 63, and 84. | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | titer | Days 0, 7, 28, 35, 56, 63, and 84 |
|
|
|
| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigens | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84 |
|
|
|
| Secondary | Geometric Mean Fold Change From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Geometric Mean | 95% Confidence Interval | fold change | Baseline (Day 0, pre-vaccination) and Days 7, 28, 35, 56, 63, and 84 |
|
|
|
| Secondary | Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Invaplex Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 28, 35, 56, 63, and 84 |
|
|
|
| Secondary | Count of Participants With 4-fold Rise From Baseline in Immunoglobulin A (IgA) Antibodies in Stool: Lipopolysaccharide (LPS) Antigen | Subjects that received the vaccination on schedule and had sufficient sample to test the antigen were included. | Posted | Count of Participants | Participants | Days 7, 28, 35, 56, 63, and 84 |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 11 |
| 12 |
| EG001 | Cohort 1: Placebo | Healthy toddlers received 3 oral doses of placebo to WRSS1 vaccine approximately 4 weeks apart. | 1 | 4 | 1 | 4 | 4 | 4 |
| Mucous stools | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Furuncle | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Gastroenteritis Escherichia coli | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Measles | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Otitis externa | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Otitis media acute | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Typhoid fever | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Varicella | Infections and infestations | MedDRA (Unspecified) | Systematic Assessment |
|
| Febrile convulsion | Nervous system disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (Unspecified) | Systematic Assessment |
|
Not provided
Not provided
| D007239 | Infections |
| D004403 | Dysentery |
| Severe |
|
| Life Threatening |
|
| None |
|
| Severe |
|
| Life Threatening |
|
| None |
|
| Severe |
|
| Life Threatening |
|
| None |
|
| Severe |
|
| Life Threatening |
|
| None |
|
| Severe |
|
| Life Threatening |
|
| None |
|
| Severe |
|
| Life Threatening |
|
| None |
|
| Severe |
|
| Life Threatening |
|
| None |
|
| Severe |
|
| Life Threatening |
|
| None |
|
| Severe |
|
| Life Threatening |
|
| None |
|
| Severe |
|
| Life Threatening |
|
| None |
|
| Severe |
|
| Life Threatening |
|
| None |
|
| Severe |
|
| Life Threatening |
|
| None |
|
| Any adverse events: Severe |
|
| Any adverse events: Life Threatening |
|
| Any adverse events: Death |
|
| Any adverse events: Total |
|
| AEs related to study vaccine: Mild |
|
| AEs related to study vaccine: Moderate |
|
| AEs related to study vaccine: Severe |
|
| AEs related to study vaccine: Life Threatening |
|
| AEs related to study vaccine: Death |
|
| AEs related to study vaccine: Total |
|
| Day 7 |
|
|
| Day 35 |
|
|
| Day 63 |
|
|
| Day 7 |
|
|
| Day 35 |
|
|
| Day 63 |
|
|
| Day 35 |
|
| Day 63 |
|
| Day 35 |
|
| Day 63 |
|
| Day 35 |
|
| Day 63 |
|
| Day 7 |
|
|
| Day 35 |
|
|
| Day 63 |
|
|
| Day 35 |
|
|
| Day 63 |
|
|
| Day 35 |
|
|
| Day 63 |
|
|
| Day 63 |
|
| Day 63 |
|
| Day 63 |
|
| Day 35 |
|
|
| Day 63 |
|
|
| Less than 4-fold rise |
|
| Day 35 |
|
|
| Day 63 |
|
|
| At any time |
|
|
| Day 35 |
|
| Day 63 |
|
| At any time |
|
| Day 35 |
|
| Day 63 |
|
| At any time |
|
| Less than 4-fold rise |
|
| Day 35 |
|
|
| Day 63 |
|
|
| At any time |
|
|
| Day 35 |
|
| Day 63 |
|
| At any time |
|
| Less than 4-fold rise |
|
| Day 35 |
|
|
| Day 63 |
|
|
| At any time |
|
|
| Day 35 |
|
| Day 63 |
|
| Day 35 |
|
| Day 63 |
|
| Day 35 |
|
| Day 63 |
|
| Day 35 |
|
| Day 63 |
|
| Day 35 |
|
| Day 63 |
|
| Day 35 |
|
| Day 63 |
|
| Day 63 |
|
| Day 63 |
|
| Day 63 |
|
| Day 63 |
|
| Day 63 |
|
| Day 63 |
|
| Day 35 |
|
| Day 63 |
|
| At any time |
|
| Day 35 |
|
| Day 63 |
|
| At any time |
|
| Day 35 |
|
| Day 63 |
|
| At any time |
|
| Day 35 |
|
| Day 63 |
|
| At any time |
|
| Day 35 |
|
| Day 63 |
|
| At any time |
|
| Day 35 |
|
| Day 63 |
|
| At any time |
|
| Day 7 |
|
|
| Day 28 |
|
|
| Day 35 |
|
|
| Day 56 |
|
|
| Day 63 |
|
|
| Day 84 |
|
|
| Day 7 |
|
|
| Day 28 |
|
|
| Day 35 |
|
|
| Day 56 |
|
|
| Day 63 |
|
|
| Day 84 |
|
|
| Day 28 |
|
|
| Day 35 |
|
|
| Day 56 |
|
|
| Day 63 |
|
|
| Day 84 |
|
|
| Day 28 |
|
|
| Day 35 |
|
|
| Day 56 |
|
|
| Day 63 |
|
|
| Day 84 |
|
|
| Less than 4-fold rise |
|
| Day 28 |
|
|
| Day 35 |
|
|
| Day 56 |
|
|
| Day 63 |
|
|
| Day 84 |
|
|
| At any time |
|
|
| Less than 4-fold rise |
|
| Day 28 |
|
|
| Day 35 |
|
|
| Day 56 |
|
|
| Day 63 |
|
|
| Day 84 |
|
|
| At any time |
|
|