The main purpose of this study is to evaluate the safety of a Shigella flexneri 2a detoxified artificial invasin complex (Invaplex\[AR-Detox\]) vaccine candidate administered by intramuscular immunization.
This is a randomized, double-blind, placebo-controlled, Phase 1 clinical trial in which a total of 60 volunteers will receive one of three doses of Invaplex\[AR-DETOX\] or placebo (saline). The vaccine will be administered via intramuscular (IM) injection on study days 1, 22, and 43. Each participant will receive the same formulation at each vaccination dependent upon group assignment. The study will be initiated with the lowest dose level (2.5 μg) and will proceed to the next highest dose in an escalating fashion. All safety data will be summarized and reviewed by the Protocol Safety Review Team (PSRT) prior to dose-escalation. Specimens will be collected at prescribed intervals to examine systemic and mucosal immune responses. Vaccine safety will be actively monitored during vaccination and for 28 days following the third vaccine dose.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
58
Detoxified Shigella flexneri 2a Artificial Invasin Complex (Invaplex\[AR-Detox\]) Vaccine
Saline
Walter Reed Army Institute of Research Clinical Trials Center (WRAIR CTC)
Silver Spring, Maryland, United States
Percentage of Participants With Adverse Events
All adverse events (AEs) were assessed for severity by the investigator according to the following scale: Grade 1 (Mild): Does not interfere with routine activities, minimal level of discomfort; Grade 2 (Moderate): Interferes with routine activities, moderate level of discomfort; Grade 3 (Severe): Unable to perform routine activities, significant level of discomfort; Grade 4 (Potentially life-threatening): Hospitalization or ER visit for potentially life-threatening event. An AE was considered "serious" if it resulted in any of the following outcomes: * Death * Life-threatening AE * Inpatient hospitalization or prolongation of existing hospitalization * Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions * Congenital anomaly/birth defect. The Investigator assessed the relationship of each adverse event to study drug.
Time frame: From first dose up to 28 days following the third immunization (71 days)
Number of Participants With Solicited Adverse Events Up to 7 Days After Dose 1
The solicited AEs for this study included: * Site pain * Site tenderness * Swelling * Induration (determined by investigator exam) * Site redness * Pruritus * Fever * Nausea * Vomiting * Abdominal pain * Diarrhea (loose stools) * Appetite change * Fatigue * Headache * Myalgias (general pain or soreness in muscles) * Arthralgias (general pain in joints) * Malaise
Time frame: 7 days after the first immunization (Days 1 to 7)
Number of Participants With Solicited Adverse Events Up to 7 Days After Dose 2
The solicited AEs for this study included: * Site pain * Site tenderness * Swelling * Induration (determined by investigator exam) * Site redness * Pruritus * Fever * Nausea * Vomiting * Abdominal pain * Diarrhea (loose stools) * Appetite change * Fatigue * Headache * Myalgias (general pain or soreness in muscles) * Arthralgias (general pain in joints) * Malaise
Time frame: 7 days after the second immunization (Days 22 to 28)
Number of Participants With Solicited Adverse Events After Dose 3
The solicited AEs for this study included: * Site pain * Site tenderness * Swelling * Induration (determined by investigator exam) * Site redness * Pruritus * Fever * Nausea * Vomiting * Abdominal pain * Diarrhea (loose stools) * Appetite change * Fatigue * Headache * Myalgias (general pain or soreness in muscles) * Arthralgias (general pain in joints) * Malaise
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Time frame: 7 days after the third immunization (Days 43 to 49)
Number of Participants With Unsolicited Adverse Events After Each Dose
Time frame: Dose 1: Days 1 to 21; Dose 2: Days 22 to 42; Dose 3: Days 43 to 71
Geometric Mean Titer (GMT) of Serum Immunoglobulin A (IgA) Antibodies to Invaplex
Time frame: Days 1 (Baseline), 22, 43, 50, 57 and 71.
Geometric Mean Titer (GMT) of Serum Immunoglobulin G (IgG) Antibodies to Invaplex
Time frame: Days 1 (Baseline), 22, 43, 50, 57 and 71.
Geometric Mean Titer (GMT) of Immunoglobulin A Antibodies to Invaplex in α4β7+ Antibody in Lymphocyte Supernatant (ALS)
Time frame: Days 1 (Baseline), 8, 29, and 50
Geometric Mean Titer of Immunoglobulin G Antibodies to Invaplex in α4β7+ Antibody in Lymphocyte Supernatant
Time frame: Days 1 (Baseline), 8, 29, and 50
Percentage of Participants With a ≥ 4-fold Increase in Serum IgA Antibodies From Baseline
Seroconversion was defined as ≥ 4-fold increase in antibody titer from Baseline.
Time frame: Days 1 (Baseline), 22 43, 50, 57 and 71
Percentage of Participants With a ≥ 4-fold Increase in Serum IgG Antibodies From Baseline
Seroconversion was defined as ≥ 4-fold increase in antibody titer from Baseline.
Time frame: Days 1 (Baseline), 22 43, 50, 57 and 71
Percentage of Participants With a ≥ 4-fold Increase in ALS IgA From Baseline
Seroconversion was defined as ≥ 4-fold increase in antibody titer from Baseline.
Time frame: Days 1 (Baseline), 8, 29, and 50
Percentage of Participants With a ≥ 4-fold Increase in ALS IgG From Baseline
Seroconversion was defined as ≥ 4-fold increase in antibody titer from Baseline.
Time frame: Days 1 (Baseline), 8, 29, and 50
Geometric Mean Fold-rise (GMFR) in Serum IgA From Baseline
Time frame: Days 1 (Baseline), 22, 43, 50, 57 and 71.
Geometric Mean Fold-rise in Serum IgG From Baseline
Time frame: Days 1 (Baseline), 22, 43, 50, 57 and 71.
Geometric Mean Fold-rise in ALS IgA From Baseline
Time frame: Days 1 (Baseline), 8, 29, and 50
Geometric Mean Fold-rise in ALS IgG From Baseline
Time frame: Days 1 (Baseline), 8, 29, and 50