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The purpose of this study is to determine whether SF2a-TT15 (a monovalent synthetic carbohydrate-based conjugate Shigella vaccine) is safe and effective in the prevention of Shigella infection.
The purpose of this study is to determine whether SF2a-TT15 (a monovalent synthetic carbohydrate-based conjugate Shigella vaccine) is safe and effective in the prevention of Shigella infection. This will be a phase 2b, double-blind, placebo-controlled, single-center study, involving a vaccination phase and a challenge phase. The vaccination phase will consist of study participants that will be 1:1 randomized to receive either the vaccine or placebo. Two doses of blinded study product will be given by intramuscular route of administration, separated by approximately 4 weeks. The challenge phase will consist of an inpatient stay of approximately 12 days during which eligible study participants will ingest an oral inoculum of wild-type S flexneri 2a strain 2457T and then be monitored for illness and treated with antibiotics when the primary endpoint is reached or upon 5 days post-challenge, whichever comes first, or when deemed necessary. Upon satisfying discharge criteria, study participants will complete outpatient clinic follow-up visits through ~7 months after last dose of blinded study product (Day 237). The efficacy study will be enrolled through three cohorts of participants, each cohort consisting of approximately 30 subjects that will be involved in the vaccination phase and 22 subjects that will proceed with the challenge phase. There will be a fourth cohort of participants, consisting of 12 subjects, that will receive the vaccine in an open-label design-this cohort will provide serum samples which are intended to be used for generating serum standards for laboratory assays, as a part of ongoing and future clinical development of Shigella vaccines.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Shigella Vaccine or Placebo, Followed by Challenge | Experimental | 1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22). |
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| Cohort 2: Shigella Vaccine or Placebo, Followed by Challenge | Experimental | 1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22). |
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| Cohort 3: Shigella Vaccine or Placebo, Followed by Challenge | Experimental | 1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22). |
|
| Cohort 4: Shigella Vaccine Only, No Challenge | Experimental | All volunteers receive the investigational Shigella vaccine (n=12). No Shigella challenge. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SF2a-TT15 Shigella Vaccine | Biological | 0.5 mL of the vaccine is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Moderate-Severe Shigellosis Illness, With Challenge | Count of participants with primary endpoint (Moderate-Severe Shigellosis) | 10 days after challenge |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Meeting Other Case Definitions and Endpoint Definitions | 10 days after challenge | |
| Number of Participants With Anti-LPS Serum IgG ELISA Response | Anti-LPS serum IgG ELISA response, by response rates (proportion of 4-fold increases from baseline, Day 1) |
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Inclusion Criteria:
WBC, ANC, Hg, Platelets Creatinine, ALT, Bili Serum IgA HIV, HBsAg, HCV Negative for HLA-B27 (this criterion does not apply to cohort 4) Stool culture urinalysis
Exclusion Criteria:
Systolic BP greater than 150 mmHg or Diastolic BP greater than 90 mmHg Resting heart rate greater than 100 Oral temperature greater than or equal to 100.4 degrees F
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland, Baltimore, Center for Vaccine Development and Global Health | Baltimore | Maryland | 21201 | United States |
Cohort 4 was eliminated prior to the start of Cohort 4 enrollment. Cohorts 1-3 are pooled and reported by vaccine vs. placebo recipients.
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| ID | Title | Description |
|---|---|---|
| FG000 | Shigella Vaccine | 1:1 randomization to investigational Shigella vaccine or placebo (n=29). The majority of participants will then receive the Shigella challenge (n=22). SF2a-TT15 Shigella Vaccine: 0.5 mL of the vaccine is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. S. flexneri 2a strain 2457T Challenge Agent: Each participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution. |
| FG001 | Placebo | 1:1 randomization to investigational Shigella vaccine or placebo (n=29). The majority of participants will then receive the Shigella challenge (n=22). Placebo: 0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. S. flexneri 2a strain 2457T Challenge Agent: Each participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Vaccination Phase |
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| Challenge Phase |
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| ID | Title | Description |
|---|---|---|
| BG000 | Vaccine | 1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22). SF2a-TT15 Shigella Vaccine: 0.5 mL of the vaccine is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Number of Participants With Moderate-Severe Shigellosis Illness, With Challenge | Count of participants with primary endpoint (Moderate-Severe Shigellosis) | All participants that were randomized to vaccine or placebo and were challenged | Posted | Count of Participants | Participants | 10 days after challenge |
|
The assessment of the safety of the vaccine was through the detection and documentation of adverse effects, both solicited AEs and unsolicited AEs, and/or clinically significant laboratory abnormalities, from enrollment through 28 days post-vaccination. Only the occurrence of SAEs were reported between Day 57 (or 28 days post-last dose of vaccine) through the end of the study (Day 237).
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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 | Vaccine Enrolled | 1:1 randomization to investigational Shigella vaccine or placebo (n=29). The majority of participants will then receive the Shigella challenge (n=22). SF2a-TT15 Shigella Vaccine: 0.5 mL of the vaccine is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. S. flexneri 2a strain 2457T Challenge Agent: Each participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Syncope | Cardiac disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Wilbur Chen | University of Maryland, Baltimore Center for Vaccine Development and Global Health (CVD) | 410-706-5328 | wchen@som.umaryland.edu |
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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 | Oct 4, 2023 | Feb 22, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 1, 2022 | Feb 22, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D004405 | Dysentery, Bacillary |
| ID | Term |
|---|---|
| D004756 | Enterobacteriaceae Infections |
| D016905 | Gram-Negative Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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| Placebo | Other | 0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. |
|
| S. flexneri 2a strain 2457T Challenge Agent | Biological | Each participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution. |
|
| Days 29, 57 and 85 |
| Anti-LPS Serum IgG ELISA Response, by Titer | Days 1, 29, 57 and 85 |
| Serum Bactericidal Activity Response, by Response Rates (Proportion of 4-fold Increases From Baseline, Day 1) | Days 29, 57 and 85 |
| Serum Bactericidal Activity Response, by Titer | Days 1, 29, 57 and 85 |
| NOT COMPLETED |
|
| Placebo |
1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22). Placebo: 0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| OG001 | Placebo | 1:1 randomization to investigational Shigella vaccine or placebo (n=30). The majority of participants will then receive the Shigella challenge (n=22). Placebo: 0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. S. flexneri 2a strain 2457T Challenge Agent: Each participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution. |
|
|
| Secondary | Number of Participants Meeting Other Case Definitions and Endpoint Definitions | Participants randomized to vaccine or placebo and were challenged | Posted | Count of Participants | Participants | 10 days after challenge |
|
|
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| Secondary | Number of Participants With Anti-LPS Serum IgG ELISA Response | Anti-LPS serum IgG ELISA response, by response rates (proportion of 4-fold increases from baseline, Day 1) | Enrolled participants | Posted | Count of Participants | Participants | Days 29, 57 and 85 |
|
|
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| Secondary | Anti-LPS Serum IgG ELISA Response, by Titer | Posted | Mean | Standard Deviation | titer | Days 1, 29, 57 and 85 |
|
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| Secondary | Serum Bactericidal Activity Response, by Response Rates (Proportion of 4-fold Increases From Baseline, Day 1) | Enrolled participants | Posted | Count of Participants | Participants | Days 29, 57 and 85 |
|
|
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| Secondary | Serum Bactericidal Activity Response, by Titer | Enrolled participants | Posted | Mean | Standard Deviation | titer | Days 1, 29, 57 and 85 |
|
|
|
| 0 |
| 29 |
| 0 |
| 29 |
| 18 |
| 29 |
| EG001 | Placebo Enrolled | 1:1 randomization to investigational Shigella vaccine or placebo (n=29). The majority of participants will then receive the Shigella challenge (n=22). Placebo: 0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. S. flexneri 2a strain 2457T Challenge Agent: Each participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution. | 0 | 29 | 0 | 29 | 21 | 29 |
| EG002 | Vaccine Challenged | 1:1 randomization to investigational Shigella vaccine or placebo (n=29). The majority of participants will then receive the Shigella challenge (n=22). Placebo: 0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. S. flexneri 2a strain 2457T Challenge Agent: Each participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution. | 0 | 22 | 0 | 22 | 0 | 22 |
| EG003 | Placebo Challenged | 1:1 randomization to investigational Shigella vaccine or placebo (n=29). The majority of participants will then receive the Shigella challenge (n=22). Placebo: 0.5 mL of normal saline is administered via an intramuscular injection into the deltoid muscle on Study Day 1 and Study Day 29. S. flexneri 2a strain 2457T Challenge Agent: Each participant will drink 120 mL of sodium bicarbonate buffer solution. Approximately 1 to 2 minutes later, the participant will ingest approximately 1500 cfu of S. flexneri 2a strain 2457T suspended in 30 mL of the bicarbonate buffer solution. | 0 | 22 | 0 | 22 | 0 | 22 |
| Abdominal Discomfort | Gastrointestinal disorders | Systematic Assessment |
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| Anorexia | Gastrointestinal disorders | Systematic Assessment |
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| Gastroenteritis | Gastrointestinal disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Injection Site Pain | General disorders | Systematic Assessment |
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| COVID-19 | Infections and infestations | Systematic Assessment |
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| Pharyngitis | Infections and infestations | Systematic Assessment |
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| Facial Injury | Injury, poisoning and procedural complications | Systematic Assessment |
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| Alanine Aminotransferase Increased | Investigations | Systematic Assessment |
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| Bilirubin Increased | Investigations | Systematic Assessment |
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| Blood Pressure Decreased | Investigations | Systematic Assessment |
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| Blood Pressure Diastolic Increased | Investigations | Systematic Assessment |
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| Blood Pressure Systolic Increased | Investigations | Systematic Assessment |
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| Heart Rate Increased | Investigations | Systematic Assessment |
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| Hemoglobin Decreased | Investigations | Systematic Assessment |
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| White Blood Cell Count Decreased | Investigations | Systematic Assessment |
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| White Blood Cell Count Increaed | Investigations | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Foot Fracture | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Wrist Pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Burn | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Ecchymosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| D007239 | Infections |
| D004403 | Dysentery |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D007410 | Intestinal Diseases |
| Count of participants with any fever endpoint |
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| Count of participants with any combination of diarrhea, dysentery, and/or fever |
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| Count of participants with serum IgG ELISA response rates, post-dose 2 (Day 57) |
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| Count of participants with serum IgG ELISA response rates, post-challenge (Day 85) |
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| Mean ±SD post-dose 1 (Day 29) |
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| Mean ±SD post-dose 2 (Day 57) |
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| Mean ±SD post-challenge (Day 85) |
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| Count post-dose 2 (Day 57) |
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| Count post-challenge (Day 85) |
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| Mean ±SD post-dose 1 (Day 29) |
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| Mean ±SD post-dose 2 (Day 57) |
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| Mean ±SD post-challenge (Day 85) |
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