A Study to Evaluate Safety and Immunogenicity of 1 Booster Dose of 1790GAHB Vaccine in Healthy Adults Primed With 3 Doses of 1790GAHB Vaccine in Study H03_01TP Compared to 1 Vaccination of 1790GAHB in Either Subjects Who Received Placebo in the Same Study or naïve Subjects Not Part of H03_01TP Study

Study Overview
=================
Brief Summary
-----------------
GVGH Shigella Sonnei 1970GAHB is a vaccine aimed at preventing the disease caused by Shigella sonnei. A post-hoc analysis of subjects who participated in the parent study showed significantly different responses in subjects with detectable versus undetectable antibody titres at baseline, suggesting the possibility that the vaccine might not be sufficiently immunogenic in completely naïve adults. This study was then designed to further characterize the immunogenicity profile of the vaccine and to evaluate whether it was able to induce an immunological memory response.

Official Title
-----------------
A Phase 1, Open Label, Non-randomized, Single Center Study to Evaluate the Safety and Immunogenicity of 1 Booster Vaccination With (GVGH Shigella Sonnei 1790GAHB) Vaccine Administered Intramuscularly in Healthy Adults Previously Primed With Three Doses of the Same Vaccine in Study H03_01TP Compared to 1 Vaccination With (1790GAHB) Administered Intramuscularly Either to Subjects Who Received Placebo in the H03_01TP Study or naïve Subjects Who Were Not Part of H03_01TP Study

Conditions
-----------------
Dysentery, Bacillary

Intervention / Treatment
-----------------
* Biological: GVGH Shigella sonnei 1790GAHB vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females, aged 22 to 50 years, who were previously vaccinated, with either vaccine (3 doses) or placebo, in H03_01TP and who had undetectable antibody titers at baseline, or Males and females, aged 22 to 50 years, who were not part of H03_01TP. Individuals who, after the nature of the study has been explained to them, and prior to any protocol specific procedures being performed, have given written consent according to local regulatory requirements. Individuals in good health as determined by the outcome of medical history, physical examination, hematological blood tests and clinical judgment of the investigator. If women of child-bearing potential, have a negative urinary pregnancy test prior study vaccination and willingness to use acceptable birth control measures for the entire study duration. Individuals affiliated to a social security regimen. 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 Guillain-Barré syndrome. Individuals who are not able to understand and to follow all required study procedures for the whole period of the study. Individuals with known hepatitis B or C or suspected HIV infection or HIV related disease with history of an autoimmune disorder or any other known or suspected impairment /alteration of the immune system. Progressive, unstable or uncontrolled clinical conditions. Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws. Abnormal function of the immune system resulting from: Clinical conditions; Systemic administration of corticosteroids for more than 14 consecutive days within 90 days prior to informed consent; Administration of antineoplastic and immunomodulating agents or radiotherapy within 90 days prior to informed consent. Received immunoglobulins or any blood products within 180 days prior to informed consent. Study personnel as an immediate family or household member. Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study. Individuals who have received an investigational product in another clinical trial 28 days prior to first study visit or intent to receive another investigational product at any time during the conduct of this study. Individuals who received any other vaccines within 4 weeks prior to enrollment in this study or who are planning to receive any vaccine within the entire study duration. Inactivated influenza vaccine can be given, but only 4 weeks earlier or 4 weeks later than the date of immunization. Individuals who have received blood, blood products, and/or plasma derivatives including parenteral immunoglobulin preparations in the past 180 days. Individuals with body temperature > 38.0 degrees Celsius within 3 days of intended study vaccination. Individuals with Body Mass Index > 30 kg/m2. Individuals with history of substance or alcohol abuse within the past 2 years. Women who are pregnant or are breast-feeding, or are of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study. Females with history of stillbirth, neonatal loss, or previous infant with anomaly. Individuals who have a previously laboratory confirmed or suspected disease caused by S. sonnei. Individuals who have had household contact with/and or intimate exposure to an individual with laboratory confirmed S. sonnei. Any condition, which, in the opinion of the investigator may pose an increased and unreasonable safety risk to the subject if participating to the present study. Individuals with a neutrophil count value lower than 1.8 10^9/L at screening assessment. Individuals with human leukocyte antigen (HLA)-B27 positive and/or with history of reactive arthritis. Previous history of Benign Ethnic Neutropenia or drug related Neutropenia and/or concomitant treatment with neutropenic agents.

Ages Eligible for Study
-----------------
Minimum Age: 22 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Shigella Group<br>Healthy male and female subjects, aged 22 to 50 years, previously primed with 3 doses of the GVGH Shigella sonnei 1790GAHB vaccine in the H03_01TP parent study and who had undetectable antibody titers at baseline, received one intramuscular booster dose of the same vaccine in the current study, at Day 1. | Biological: GVGH Shigella sonnei 1790GAHB vaccine<br>* Single dose administered at Day 1, by intramuscular injection.<br>|
| Experimental: Placebo Group<br>Healthy male and female subjects, aged 22 to 50 years, who previously received placebo in the H03_01TP parent study and who had undetectable antibodies at baseline, received one intramuscular GVGH Shigella sonnei 1790GAHB vaccine dose in the current study, at Day 1. | Biological: GVGH Shigella sonnei 1790GAHB vaccine<br>* Single dose administered at Day 1, by intramuscular injection.<br>|
| Experimental: Naïve Group<br>Healthy male and female subjects, aged 22 to 50 years, who were not part of H03_01TP parent study, received one intramuscular GVGH Shigella sonnei 1790GAHB vaccine dose in the current study, at Day 1. | Biological: GVGH Shigella sonnei 1790GAHB vaccine<br>* Single dose administered at Day 1, by intramuscular injection.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of Immunoglobulin (IgG) Against Lipopolysaccharide (LPS) S. Sonnei O-antigen | IgG concentrations are expressed as Geometric Mean Concentrations (GMCs), as determined by the Enzyme-linked immunosorbent assay (ELISA) with Shigella sonnei (S.sonnei) O-antigen containing Lipopolysaccharide (LPS) coating antigen. Concentrations are presented as GMCs expressed in ELISA units per milliliter (EU/mL). | At Day 8 (7 days after vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Abnormal Haematological Test Values | Assessed haematological parameters are: basophils (BAS), eosinophils (EOS), erythrocytes (ERCS), hematocrit (HCT), hemoglobin (HGB), leukocytes (LKCS), lymphocytes (LYM), monocytes (MONO), neutrophils (NEU) and platelet (PLT). | At Day 8 (7 days after vaccination) and Day 85 (84 days after vaccination) | 
| Number of Subjects With Solicited Local Adverse Events | Assessed solicited local adverse events include injection site erythema, injection site induration and injection site pain. Any symptom = occurrence of the symptom regardless of intensity grade. | From 30 minutes through Day 7 post-vaccination | 
| Number of Subjects With Solicited Systemic Adverse Events | Assessed solicited systemic adverse events include arthralgia, chills, fatigue, headache, malaise, myalgia and oral fever. Other indicators of solicited adverse events include prevention of pain and/or fever and treatment of pain and/or fever. Any symptom = occurrence of the symptom regardless of intensity grade. Fever = body temperature (measured orally) equal to or above (≥) 38.0 °C. | From 30 minutes through Day 7 post-vaccination | 
| Number of Subjects With Unsolicited Adverse Events | An unsolicited adverse event (AE) is an adverse event that was not solicited using a Subject Diary 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. Any = occurrence of the symptom regardless of intensity grade. Grade 3 AE = AE that prevented daily activity. Possibly/probably related AE = AE determined by the investigator as possibly related (the administration of the investigational vaccine and AE are considered reasonably related in time and the AE could be explained by exposure to the investigational vaccine or by other causes) or probably related (exposure to the investigational vaccine and AE are reasonably related in time and no alternative explanation has been identified) to the study vaccination. | Throughout the study period (From Day 1 up to Day 85) | 
| Number of Subjects With Serious Adverse Events (SAEs) | A serious adverse event is defined as an untoward medical occurrence that at any dose resulted in death, was life-threatening, required hospitalization or prolonged hospitalization, resulted in persistent or significant disability/incapacity, or in a congenital anomaly/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. | Throughout the study period (from Day 1 up to Day 85) | 
| Concentrations of IgG Against LPS S. Sonnei O-antigen | Concentrations of IgG against S.sonnei O-antigen are presented as GMCs, expressed in ELISA units per milliliter (EU/mL). | At Days 15, 29 and 85 (14, 28 and 84 days after vaccination) | 
| Anti-LPS S. Sonnei IgG Geometric Mean Ratios | Within-subject Geometric mean ratios (GMRs) were computed for GMCs at 7, 14, 28 and 84 days after vaccination versus baseline (Day 1). The GMRs and 95% confidence intervals (CIs) were constructed by exponentiating the mean within-subject differences in log-transformed concentrations and the corresponding 95% CIs. | At Days 8, 15, 29 and 85 (7, 14, 28 and 84 days after vaccination) | 
| Percentage of Subjects With Seroresponse for Anti-LPS S. Sonnei | Seroresponse is aimed to define a significant increase in post-vaccination samples based on the biological performance of this specific serology assay and it is defined as follows: - If the baseline value is greater than 50 ELISA Units (EU) then an increase of at least 50% in the post-vaccination sample as compared to baseline [i.e. ((Post-vac minus baseline)/baseline)100% ≥ 50%]. - If the baseline value is less or equal to 50 EU then an increase of at least 25 EU in the post-vaccination sample as compared to baseline [i.e. (Postvac minus baseline) ≥ 25 EU. | At Days 8, 15, 29 and 85 (7, 14, 28 and 84 days after vaccination) | 
| Percentage of Subjects With Anti-LPS S. Sonnei Concentrations Equal to or Above (≥) 121 EU/mL | Anti-LPS S.sonnei antibody concentrations were assessed by ELISA. The assay cut-off value was 121 EU/mL. | At Days 8, 15, 29 and 85 (7, 14, 28 and 84 days after vaccination) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Immunogenicity, Vaccine, Immunologic Memory, GMMA, Shigella Vaccines, Shigellosis, Dysentery, Bacillary, Healthy Volunteers, Safety, Bacteria, Clinical Trials, Phase 1, Shigella sonnei