A Phase 2a, Observer Blind, Randomized, Controlled, Single Center Study To Evaluate The Safety, Reactogenicity And Immunogenicity Of 2 Doses Of The GVGH 1790GAHB Vaccine Against Shigella Sonnei, Administered Intramuscularly In Adult Subjects From A Country Endemic For Shigellosis
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Shigella Sonnei Infection
- Sponsor
- GlaxoSmithKline
- Enrollment
- 74
- Locations
- 1
- Primary Endpoint
- Number of Subjects With Serious Adverse Events (SAEs)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and the immunogenicity of two different doses of the GVGH S. sonnei vaccine in healthy adults and represents the first step towards testing of the GMMA vaccine in the vaccine target population of children from developing countries where shigellosis is endemic.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Individuals ≥18 years to ≤45 years of age on the day of informed consent who are resident in the study area and are not planning to leave during the study period.
- •Individuals who, after the nature of the study has been explained, have voluntarily given written consent according to local regulatory requirements, prior to study entry.
- •Individuals who can comply with study procedures including follow-up.
- •Individuals in good health as determined by the outcome of medical history, physical examination, hematology, renal function, and liver function tests, urine dipstick/urinalysis and the clinical judgment of the investigator.
- •Males Or Females of childbearing potential who are using an effective birth control method which they intend to use for the duration of the study Or Females without childbearing potential (i.e. irrespective of birth control method) Prior to receipt of second study vaccination, subjects must be evaluated to confirm that they are eligible for subsequent vaccination. If subjects do not meet any of the original inclusion criteria listed above, they should not receive additional vaccinations.
Exclusion Criteria
- •Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.
- •Individuals with any progressive or severe neurological disorder, seizure disorder or previous Guillain-Barré syndrome.
- •Individuals who, in the judgment of the investigator, may not be able to comply with all the required study procedures.
- •Individuals with history of any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study.
- •Individuals with history of reactive arthritis.
- •Individuals with known HIV or hepatitis B virus infection or HIV related disease, history of an autoimmune disorder or any other known or suspected impairment /alteration of the immune system. Individuals under systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to screening.
- •Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
- •Individuals with a neutrophil count lower than 1.8 x 10\^9/L (applicable to the initial 18 subjects) or lower than 1.0 x 10\^9/L (applicable to the additional subjects if approved by DSMB) at screening
- •Individuals with any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, Type 2 diabetes mellitus, hypertension, cardiac, renal or hepatic disease and tuberculosis).
- •Individuals who have any malignancy or lymphoproliferative disorder.
Outcomes
Primary Outcomes
Number of Subjects With Serious Adverse Events (SAEs)
Time Frame: Throughout the whole study period (from Day 1 up to Day 57)
An SAE is defined as any untoward medical occurrence that at any dose results in one or more of the following: death; is life-threatening (i.e., the subject was, in the opinion of the investigator, at immediate risk of death from the event as it occurred); it does not refer to an event which hypothetically might have caused death if it were more severe; required or prolonged hospitalization; persistent or significant disability/incapacity (i.e., the event causes a substantial disruption of a person's ability to conduct normal life functions); congenital anomaly/or birth defect; an important and significant medical event that may not be immediately life-threatening or resulting in death or hospitalization but, based upon appropriate medical judgment, may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above.
Number of Subjects With Deviations From Normal Ranges of Safety Laboratory Data at Day 8 by Baseline Ranges
Time Frame: At Day 8 (7 days after first vaccination)
The safety laboratory data included haematological parameters (basophils, eosinophils, erytrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, platelets and neutrophils), and chemical parameters (Alkaline Phosphatase \[ALP\], Alanine Aminotransferase \[ALA\], Aspartate Aminotransferase \[AST\], Bilirubin \[BILI\], Blood Urea Nitrogen \[BUN\], Creatinine \[CREAT\], Gamma Glutamyl Transferase \[GGT\], Glucose \[GLUC\], Potassium \[K\], Lactate Dehydrogenase \[LDH\] and Sodium \[Na\]). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Number of Subjects With Solicited Local and Systemic Adverse Reactions After Each Vaccination
Time Frame: From 30 minutes up to 7 days following each vaccination
Assessed solicited local adverse reactions were injection site erythema, induration, pain. Assessed systemic adverse reactions were headache, arthralgia, chills, fatigue, malaise, myalgia and temperature (body temperature measured axillary). Any = occurrence of the symptom regardless of intensity grade. Any temperature = body temperature ≥ 38.0°C. Severe symptom = pain, headache, arthralgia, chills, fatigue, malaise and myalgia that prevented normal activity. Severe redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. Severe temperature = body temperature \> 40.0 °C.
Number of Subjects With Any Unsolicited Adverse Events (AEs)
Time Frame: During 28 days following each vaccination
An unsolicited AE is an AE that was not solicited using the Diary Card and that was spontaneously communicated by a subject who has signed the informed consent. Potential unsolicited AEs may be medically attended (defined as symptoms or illnesses requiring hospitalization, or emergency room visit, or visit to/by a health care provider), or were of concern to the subject. Note: \*disruptions= dose reduction, interruption or delay in study vaccination.
Number of Subjects With Deviations From Normal Ranges of Safety Laboratory Data at Day 29 by Baseline Ranges
Time Frame: At Day 29 (28 days after the first vaccination)
The safety laboratory data included haematological parameters (basophils, eosinophils, erytrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, platelets and neutrophils), and chemical parameters (Alkaline Phosphatase \[ALP\], Alanine Aminotransferase \[ALA\], Aspartate Aminotransferase \[AST\], Bilirubin \[BILI\], Blood Urea Nitrogen \[BUN\], Creatinine \[CREAT\], Gamma Glutamyl Transferase \[GGT\], Glucose \[GLUC\], Potassium \[K\], Lactate Dehydrogenase \[LDH\] and Sodium \[Na\]). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Number of Subjects With Deviations From Normal Ranges of Safety Laboratory Data at Day 36 by Baseline Ranges
Time Frame: At Day 36 (7 days after the second vaccination)
The safety laboratory data included haematological parameters (basophils, eosinophils, erytrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, platelets and neutrophils), and chemical parameters (Alkaline Phosphatase \[ALP\], Alanine Aminotransferase \[ALA\], Aspartate Aminotransferase \[AST\], Bilirubin \[BILI\], Blood Urea Nitrogen \[BUN\], Creatinine \[CREAT\], Gamma Glutamyl Transferase \[GGT\], Glucose \[GLUC\], Potassium \[K\], Lactate Dehydrogenase \[LDH\] and Sodium \[Na\]). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Number of Subjects With Reported Reactive Arthritis or Neutropenia (AESIs)
Time Frame: Throughout the whole study period (from Day 1 up to Day 57)
Reactive arthritis is defined as non-purulent joint inflammation that develops in response to an infection in another part of the body. Since the inflammation is triggered by a previous condition, it is termed "reactive". Intestinal pathogens that have been associated with reactive arthritis include Campylobacter, Salmonella, Yersinia, Clostridium difficile, and Shigella. If reactive arthritis is caused by an auto immune response, there is at least a possibility that it could be initiated by vaccination of susceptible people with the 1790GAHB vaccine.
Number of Subjects With Deviations From Normal Ranges of Safety Laboratory Data at Day 57 by Baseline Ranges
Time Frame: At Day 57 (28 days after the second vaccination)
The safety laboratory data included haematological parameters (basophils, eosinophils, erytrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, platelets and neutrophils), and chemical parameters (Alkaline Phosphatase \[ALP\], Alanine Aminotransferase \[ALA\], Aspartate Aminotransferase \[AST\], Bilirubin \[BILI\], Blood Urea Nitrogen \[BUN\], Creatinine \[CREAT\], Gamma Glutamyl Transferase \[GGT\], Glucose \[GLUC\], Potassium \[K\], Lactate Dehydrogenase \[LDH\] and Sodium \[Na\]). Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Secondary Outcomes
- Number of Subjects With Titers Post Vaccination Concentration for Anti-LPS S. Sonnei ≥ 121 U/mL(At Day 1, Day 29 (28 days after the first vaccination) and Day 57 (28 days after the second vaccination))
- Anti-LPS S. Sonnei Geometric Mean Ratios (GMRs) Between Post- and Pre-vaccination Samples(At Day 1, Day 29 (28 days after the first vaccination) and Day 57 (28 days after the second vaccination))
- Number of Subjects With Seroresponse to Anti-LPS S. Sonnei IgG ELISA, by Baseline Titer(At Day 29 (28 days after the first vaccination) and Day 57 (28 days after the second vaccination))
- Anti-LPS S.Sonnei IgG ELISA Geometric Mean Concentrations (GMCs), by Baseline Titer(At Day 1, Day 29 (28 days after the first vaccination) and Day 57 (28 days after the second vaccination))