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
Phase: PHASE1
Conditions: Dysentery, Bacillary
Sponsor: GlaxoSmithKline

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CLINICAL STUDY PROTOCOL H03_01E1TP   
Version  
  
1  
  
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  
  
Shigella sonnei GMMA vaccine in healthy French adult extension Phase I vaccine trial  
  
  
  
  
  
  
  
  
Property of GlaxoSmithKline Biologicals SA (hereafter referred to as GSK Bio)  
  
Confidential  
May not be used, divulged, published or otherwise disclosed without written consent 
of GlaxoSmithKline Biologicals SA  
TABLE OF CONTENTS  
TABLE OF CONTENTS .................................................................................................... 1 
PROTOCOL SYNOPSIS [H03_01E1TP, VERSION 1] .................................................... 6 

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Table 2 Time and Event Table- Treatment Period ........................................................ 24 
Table 3 Safety Tests Table ............................................................................................ 27 
LIST OF ABBREVIATIONS ........................................................................................... 29 
1.  BACKGROUND AND RATIONALE ......................................................................... 31 
1.1  Background ............................................................................................................ 31 
1.2  Rationale ................................................................................................................. 32 
2.  OBJECTIVES ............................................................................................................... 32 
2.1  Primary Objective(s) .............................................................................................. 32 
2.2  Secondary Objective(s) .......................................................................................... 33 
2.3  Exploratory Objective(s) ........................................................................................ 33 
3.  STUDY DESIGN .......................................................................................................... 34 
3.1 Overview of Study Design ...................................................................................... 34 
3.2 Study Period ............................................................................................................ 35 
3.3  Blinding Procedures ............................................................................................... 35 
3.4  Data Collection ....................................................................................................... 35 
3.4.1  Data Collected from Subjects ......................................................................... 35 
3.4.2  Tools Used for Data Collection ...................................................................... 36 
3.5  Collection of Clinical Specimens ........................................................................... 37 
3.6  Stopping/Pausing Guidelines ................................................................................. 39 
3.7  Data Monitoring Committee .................................................................................. 39 
3.8  Premature Withdrawal from Study......................................................................... 40 
3.9  End of Study ........................................................................................................... 42 
4.  SELECTION OF STUDY POPULATION .................................................................. 42 
4.1 Inclusion Criteria ..................................................................................................... 42 
4.2 Exclusion Criteria .................................................................................................... 43 
4.3  Criteria for Delay of Vaccination ........................................................................... 44 
5.  STUDY PROCEDURES .............................................................................................. 45 
5.1  Pre-vaccination Clinic Visit(s) ............................................................................... 45 
5.1.1  Informed Consent/Assent ............................................................................... 45 
5.1.2  Screening ........................................................................................................ 46 
5.1.3  Enrolment ........................................................................................................ 47 
5.1.4  Randomization ................................................................................................ 47 
5.1.4.1 Randomization ......................................................................................... 47 
5.2  Vaccination Clinic Visit(s) ..................................................................................... 47 
5.2.1  Post-vaccination Procedures ........................................................................... 48 
5.2.2  Post-vaccination Reminders ........................................................................... 49 
5.3  Post-vaccination Visit(s) ........................................................................................ 50 
5.3.1  Follow-up Clinic Visit(s) ................................................................................ 50 
5.3.2  Safety Follow-up Calls ................................................................................... 50 
5.4  Unscheduled Visits ................................................................................................. 50 
5.5  Study Termination Visit ......................................................................................... 51 
5.5.1  Early Termination Visit .................................................................................. 51 

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6. TREATMENT OF SUBJECTS ..................................................................................... 52 
S6.1 Study Vaccine(s) ................................................................................................... 52 
For further information of study vaccines refer to the Investigator Brochure .............. 53 
6.2  Non-Study Vaccines ............................................................................................... 53 
6.3  Vaccine Preparation and Administration ............................................................... 53 
6.3.1 Replacement of unusable vaccines .................................................................. 54 
6.4  Vaccine Administration Error or Overdose of Vaccine ......................................... 54 
6.5  Prior and Concomitant Medications and Vaccines ................................................ 54 
6.6  Vaccine Supply, Labeling, Storage and Tracking .................................................. 55 
7.  ASSESSMENTS ........................................................................................................... 56 
7.1  Safety Assessment .................................................................................................. 56 
7.1.1 Solicited Adverse Events ................................................................................. 57 
7.1.2 Unsolicited Adverse Events ............................................................................. 59 
7.1.3  Evaluation of Adverse Events ......................................................................... 59 
7.1.4  Serious Adverse Events .................................................................................. 61 
7.1.4.1 Adverse Events of Special Interest .......................................................... 63 
7.1.5  Methods for Recording Adverse Events and Serious Adverse Events ........... 63 
7.1.5.1 Post-Study Events .................................................................................... 64 
7.1.6  Pregnancies ..................................................................................................... 64 
7.1.7  Safety Laboratory Measurements ................................................................... 65 
7.2  Efficacy Assessment............................................................................................... 66 
7.3  Immunogenicity Assessment .................................................................................. 66 
8.  STATISTICAL CONSIDERATIONS .......................................................................... 67 
8.1  Endpoints ................................................................................................................ 67 
8.1.1  Primary Endpoint(s) ........................................................................................ 67 
8.1.1.1 Primary Safety Endpoint(s) ..................................................................... 67 
8.1.1.2 Primary Efficacy Endpoint(s) .................................................................. 67 
8.1.1.3 Primary Immunogenicity Endpoint(s) ..................................................... 67 
8.1.2  Secondary Endpoint(s) .................................................................................... 67 
8.1.2.1 Secondary Safety Endpoint(s) ................................................................. 67 
8.1.2.2 Secondary Efficacy Endpoint(s) .............................................................. 67 
8.1.2.3 Secondary Immunogenicity Endpoint(s) ................................................. 67 

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8.1.3  Exploratory Endpoint(s) ................................................................................. 68 
8.1.3.1 Exploratory Safety Endpoint(s) ............................................................... 68 
8.1.3.2 Exploratory Efficacy Endpoint(s) ............................................................ 68 
8.1.3.3 Exploratory Immunogenicity Endpoint(s) ............................................... 68 
8.2  Success Criteria ...................................................................................................... 69 
8.2.1  Success Criteria for Primary Objective(s) ........................................................ 6 
8.2.1.1 Success Criteria for Primary Safety Objective(s) ...................................... 6 
8.2.1.2 Success Criteria for Primary Efficacy Objective(s)................................... 6 
8.2.1.3 Success Criteria for Primary Immunogenicity Objective(s) ...................... 6 
8.2.2  Success Criteria for Secondary Objective(s) .................................................... 6 
8.2.2.1 Success Criteria for Secondary Safety Objective(s) .................................. 6 
8.2.2.2 Success Criteria for Secondary Efficacy Objective(s) ............................... 6 
8.2.2.3 Success Criteria for Secondary Immunogenicity Objective(s) .................. 6 
8.3  Analysis Sets ............................................................................................................ 6 
8.3.1  All Enrolled Set ................................................................................................ 6 
8.3.2  All Exposed Set ................................................................................................ 6 
8.3.3  Safety Set .......................................................................................................... 6 
8.3.4  Full Analysis Set (FAS) Efficacy/Immunogenicity Set ................................... 6 
8.3.5  Per Protocol (PP) Immunogenicity Set ............................................................. 6 
8.3.6  Other Analysis Sets .......................................................................................... 6 
8.3.7  Subgroups ......................................................................................................... 6 
8.3.8  Protocol Deviations .......................................................................................... 6 
8.4  Statistical Analysis Plan ........................................................................................... 6 
8.4.1  Analysis of Demographic and Baseline Characteristics ................................... 6 
8.4.2  Analysis of Primary Objective(s) ..................................................................... 6 
8.4.2.1 Analysis of Primary Safety Objective(s) ................................................... 6 
8.4.2.1.1  Analysis of Extent of Exposure ........................................................... 6 
8.4.2.1.2  Analysis of Solicited Local, Systemic and Other Adverse Events ...... 6 
8.4.2.1.3  Analysis of Unsolicited Adverse Events ............................................. 6 
8.4.2.1.4  Analysis of Safety Laboratory Values ................................................. 6 
8.4.2.2 Analysis of Primary Efficacy Objective(s) ................................................ 6 
8.4.2.2.1  Statistical Hypotheses .......................................................................... 6 
8.4.2.2.2  Analysis Sets ....................................................................................... 6 
8.4.2.2.3  Statistical Methods .............................................................................. 6 
8.4.2.3 Analysis of Primary Immunogenicity Objective(s) ................................... 6 
8.4.2.3.1  Statistical Hypotheses .......................................................................... 6 
8.4.2.3.2  Analysis Sets ....................................................................................... 6 
8.4.2.3.3  Statistical Methods .............................................................................. 6 
8.4.3  Analysis of Secondary Objective(s) ................................................................. 6 
8.4.3.1 Analysis of Secondary Safety Objective(s) ............................................... 6 
8.4.3.1.1  Analysis of Extent of Exposure ........................................................... 6 
8.4.3.1.2  Analysis of Solicited Local, Systemic and Other Adverse Events ...... 6 

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8.4.3.1.3  Analysis of Unsolicited Adverse Events ............................................. 6 
8.4.3.1.4  Statistical Hypotheses .......................................................................... 6 
8.4.3.1.5  Analysis Sets ....................................................................................... 6 
8.4.3.1.6  Statistical Methods .............................................................................. 6 
8.4.3.2 Analysis of Secondary Efficacy Objective(s) ............................................ 6 
8.4.3.2.1  Statistical Hypotheses .......................................................................... 7 
8.4.3.2.2  Analysis Sets ....................................................................................... 7 
8.4.3.2.3  Statistical Methods .............................................................................. 7 
8.4.3.3 Analysis of Secondary Immunogenicity Objective(s) ............................... 7 
8.4.3.3.1  Statistical Hypotheses .......................................................................... 7 
8.4.3.3.2  Analysis Sets ....................................................................................... 7 
8.4.3.3.3  Statistical Methods .............................................................................. 7 
8.4.4  Analysis of Exploratory Objectives .................................................................. 7 
8.4.4.1 Analysis of Exploratory Safety Objective(s) ............................................. 7 
8.4.4.2 Analysis of Exploratory Efficacy Objective(s).......................................... 7 
8.4.4.3 Analysis of Exploratory Immunogenicity Objective(s) ............................. 7 
8.5  Sample Size and Power Considerations of Primary and Secondary Objectives ...... 7 
8.6  Interim Analysis ....................................................................................................... 7 
9.  SOURCE DOCUMENTATION, STUDY MONITORING AND AUDITING ............ 7 
9.1  Source Documentation ............................................................................................. 7 
9.2  Study Monitoring, Auditing and Source Data Verification ..................................... 7 
10.  DATA MANAGEMENT .............................................................................................. 7 
10.1 Data Entry and Management ................................................................................... 7 
10.2 Data Clarification .................................................................................................... 7 
10.3 Data Protection ........................................................................................................ 7 
11.  RECORD RETENTION ............................................................................................... 7 
12.  USE OF INFORMATION AND PUBLICATION ....................................................... 7 
13.  ETHICAL CONSIDERATIONS .................................................................................. 7 
13.1 Regulatory and Ethical Compliance ........................................................................ 7 
13.2 Informed Consent Procedures ................................................................................. 7 
13.3 Responsibilities of the Investigator and IRB/EC .................................................... 7 
13.4 Protocol Amendments ............................................................................................. 7 

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14. REFERENCE LIST ....................................................................................................... 7 
APPENDIX 1: INVESTIGATOR AGREEMENT ............................................................. 7 
 
PROTOCOL SYNOPSIS [H03_01E1TP, Version 1]  
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  
Title of Study:   
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.  
Study Period: Each subject will be 
followed-up for 84 days (approximately 3 
months) after vaccination   
Clinical Phase: Phase 1  

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Background and Rationale: The trial H03_01TP evaluated the safety and 
immunogenicity profile of 5 different doses of GVGH Shigella sonnei 1790GAHB 
vaccine (1 µg to 100 µg) compared to placebo, when administered in 3 injections to 50 
healthy adults. The immunogenicity was evaluated at baseline, 28 days after each 
vaccination and at 168 days after third vaccination, by measuring the anti-LPS S. sonnei 
serum IgG. Overall, an antibody response was observed across all the vaccine groups. 
However, at most of the time points, the response was higher in subjects who received 
higher antigen doses (e.g., 25 µg, 50 µg, and 100 µg) than those who received lower doses 
(e.g., 1 µg and 5µg). More specifically, a vaccine dose of 25 µg was very well tolerated 
and induced median antibody concentrations above 121 EU/mL at all post vaccination 
time points. Since 121 EU/mL is the median antibody titer in a panel of 87 convalescents 
previously exposed to S. sonnei infection and therefore protected against re-infection from 
the same serotype, a vaccine dose of 25 µg has the potential to be protective when 
included in a vaccine against S. sonnei.   
After unblinding the immunogenicity database, it was observed that the trial subjects 
could be classified in 2 groups based on S. sonnei antibody concentration at baseline, with 
approximately 50% having undetectable and the other 50% having detectable antiLPS S. 
sonnei serum IgG antibody concentrations. Therefore, for a better understanding of the 
immunological response induced by the vaccine in naïve and primed subjects and for a 
better planning of new clinical studies, additional analyses were carried out. To mitigate 
the small size of study groups, subjects who received vaccines containing 1 µg and 5 µg 
antigen/dose were combined into a single group and then stratified by the presence or 
absence of detectable antibodies at baseline. Same was done for subjects who received 
vaccines containing 25 µg, 50 µg, and 100 µg antigen/dose. As shown in  
 
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  

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Figure 1 below, subjects vaccinated with 25 µg, 50 µg and 100 µg vaccines, with 
detectable antibody concentrations at baseline, showed, at all-time points (1 month after 
the first, second and the third vaccinations and 6 months after the third vaccination), 
median antibody concentrations far higher than 121 EU/mL. Subjects vaccinated with 1 
µg and 5 µg vaccines, with detectable antibody concentrations at baseline, showed median 
antibody concentrations slightly higher than 121 EU/mL only at 1 month after the third 
vaccination.  
Figure 1: Median anti-LPS S. sonnei IgG ELISA concentrations and interquartile range 
in subjects with detectable antibodies at baseline (subjects with data at all visits)  
  
Figure 2 below,  with  subjects vaccinated with 25 µg, 50 µg and 100 µg vaccines, with 
undetectable antibody concentrations at baseline, showed median antibody concentrations 
higher than 121 EU/mL at 1 month after the first, second and the third vaccination, while 
at 6 months after the third vaccination the median antibody concentration was less than 
121 EU/mL. Subjects vaccinated with 1 µg and 5 µg vaccines, with undetectable antibody 
concentrations at baseline, did not reach the 121 EU/mL threshold at any time point.  
Figure 2: Median anti-LPS S. sonnei IgG ELISA concentrations and interquartile range 
in subjects with undetectable antibodies at baseline (subjects with data at all visits)  
 
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  

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The results from H03_01TP suggest that GVGH S. sonnei 1790GAHB vaccine, even if 
administered at high doses, may not be sufficiently immunogenic in completely naïve 
adults (who might be a better predictor of antibody response in young naïve children, the 
ultimate target for this vaccine). Although the schedule of immunization used in the trial 
(i.e., 3 injections 1 month apart) may have not been optimal, it remains important to 
evaluate whether the vaccine was able to induce an immunological memory response.  
Therefore the current H03_01E1TP study is designed to further characterize the 
immunogenicity profile of GVGH S. sonnei 1790GAHB vaccine and obtain useful 
information for further clinical development through the administration of a booster dose 
to individuals with undetectable antibodies at baseline in H03_01TP, approximately two 
to three years (i.e. 24 to 36 months) after the third vaccine dose, compared to 
administration of 1 single vaccine dose to placebo recipients with undetectable antibodies 
at baseline in H03_01TP or to naïve subjects who were not part of H03_01TP study. The 
naïve subjects who were not part of H03_01TP study are added in order to have a more 
balanced number of previously unvaccinated and vaccinated subjects in the extension 
trial. In light of the safety and immunogenicity results of H03_01TP and of the potential 
development of a S. sonnei containing Shigella multivalent vaccine, a dose of 25 µg would 

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be preferable for further development. Therefore, the use of this antigen dose is proposed 
for immunization of all subjects to provide further useful information for a more complete 
characterization of this vaccine strength.  
Study Objectives:   
 

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managed in Atlas) / Version Date: June 8, 2016  
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  

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Primary Objective(s):   
To evaluate the memory response, as measured by anti-LPS S. sonnei serum IgG, 7 days 
after vaccination with a booster dose of GVGH S. sonnei 1790GAHB vaccine in 
individuals who had undetectable antibody titers at baseline in H03_01TP, approximately 
two to three years after the third vaccine dose, compared to administration of 1 single 
vaccine dose to placebo recipients with undetectable antibody titers at baseline in 
H03_01TP or naïve subjects who were not part of H03_01TP study.    
Secondary Objective(s):   
1) Safety:  
a. To evaluate the safety profile of one dose of GVGH S. sonnei 1790GAHB vaccine 
in subjects who previously received three vaccinations with 1790GAHB and in 
subjects receiving one dose 1790GAHB for the first time (either placebo 
recipients in H03_01TP or naïve subjects who were not part of H03_01TP study).  
b. To evaluate the safety profile of one dose of GVGH S. sonnei 1790GAHB vaccine 
in subjects receiving one dose 1790GAHB for the first time and having detectable 
antibodies at baseline of the extension trial.  
2) Immunogenicity:  
a. To evaluate the immunogenicity profile 7, 14, 28 and 84 days after vaccination 
with one dose of GVGH S. sonnei 1790GAHB vaccine in subjects with 
undetectable antibody titers at baseline who previously received three 
vaccinations of GVGH S. sonnei 1790GAHB vaccine in H03_01TP and in 
placebo recipients with undetectable antibody titers at baseline in H03_01TP or 
naïve subjects who were not part of H03_01TP study.  
b. To evaluate the immunogenicity profile of one dose of GVGH S. sonnei 
1790GAHB vaccine in subjects receiving one dose 1790GAHB for the first time 
and having detectable antibodies at baseline of the extension trial.  
c. To evaluate the persistence of anti-LPS S. sonnei serum IgG antibody titers 
approximately two to three years after the third vaccination with 1790GAHB. 3) 
Exploratory:   
Other immunological assays might be performed to further characterize the immune 
response to the study vaccine including serum secretory IgA.  
Study Design:   
 

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Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  
This is an open label, non-randomized, single center, Phase 1 clinical trial.  The study 
includes a screening visit (performed at study Days -21to -1), one clinical visit with 
vaccination (performed at study Day 1), 4 clinical visits (performed 7, 14, 28 and 84 days 
after vaccination), and 2 phone calls (performed 2 and 6 days after the vaccination).  
Table 1 H03_01TP Study Design    
 H03_01TP    
H03_01E1TP  
Vaccine 
group  
No.  
subjects*  
New enrolled 
subjects  
No. subjects  
 
Vaccine group  
1790GAHB – 1 µg**  
5  
  
5  
1790GAHB – 25 µg  
1790GAHB – 5 µg  
4  
  
4  
1790GAHB – 25 µg  
1790GAHB – 25 µg  
2  
  
2  
1790GAHB – 25 µg  
1790GAHB – 50 µg  
4  
  
4  
1790GAHB – 25 µg  
1790GAHB – 100 µg  
5  
  
5  
1790GAHB – 25 µg  
Placebo  
4  
  
4  
1790GAHB – 25 µg  
Total H03_01TP  
24  
Naïve subjects   
26  
1790GAHB – 25 µg  
Grand total   
 
  
50  
 
 *only subjects with undetectable antibodies at baseline.  
  
  
** µg of total protein  
  

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Number of Subjects planned:   
Up to 50 subjects will be enrolled into this trial.  Up to 24 subjects are eligible from the 
parent H03_01TP trial. With respect to naïve subjects who were not part of H03_01TP 
study, considering that in the original H03_01TP population 50% of subjects did not have 
detectable antibodies at baseline, with 26 subjects, approximately 13 subjects should not 
have detectable antibodies. This number combined with that of placebo recipients in 
H03_01TP should be sufficient to allow a balanced contribution of previously 
unvaccinated and vaccinated subjects in the extension trial. Subjects withdrawn or lost to 
follow up will not be replaced. The sample size is not driven by any statistical hypothesis, 
but by availability of subjects from H03_01TP study and fulfilling inclusion criteria.  
Study Population and Subject Characteristics:   
The study population will consist of adult healthy volunteer subjects meeting all inclusion 
and no exclusion criteria.  
The list of inclusion and exclusion criteria is included in protocol section 4, Selection of  
 
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  
Study Population.   

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Study Procedures:   
Before any study procedure is performed, informed consent will be obtained; subjects 
will be enrolled only after their eligibility for participation is confirmed by the 
investigator. Safety procedures:  
All subjects providing informed consent will undergo review of medical history, a general 
physical examination including vital signs measurement (temperature, respiratory rate, 
heart rate, blood systolic and diastolic pressure) at the screening visit (study Days -21 to-
1) and at Visit 1 (Day 1) for evaluation of the general health status by clinical assessment 
and verification of inclusion and exclusion criteria. At clinic Visit 2 and at subsequent 
visits, a brief symptom-directed physical examination (if necessary according to 
symptoms the subject has reported) will be performed. Throughout the study it will be 
checked whether continued participation in the study is in the subject best interest in terms 
of safety. For all women of childbearing potential before vaccination at visit 1, a urine 
pregnancy test will be conducted and will also be repeated at visit 5 (Day 85). Women 
with positive test or refusing to perform the test will be immediately excluded from the 
study. Female subjects must use acceptable (defined as oral, injected or implantable 
contraceptives) birth control measures during study participation.  
Blood Draw Procedure:  
Approximately 15 mL blood draw will be obtained for hematological and serological 
(HIV, hepatitis B and C) for subjects who were part of the parent trial (H03_01TP). For 
naïve subjects however 25 mL of blood draw will be obtained for the same hematological 
and serological test mentioned above and in addition HLA-B27 testing as part of the initial 
screening. One additional blood draw of 6 mL for hematological tests will be obtained at 
7 days (Visit 2) and 84 days (Visit 5) after vaccination (see Table 2). Each subject will 
have 20 mL of blood drawn for immunological studies before and 7, 14, 28 and 84 days 
after vaccination. For the purpose of creating a standard reference serum for the 
serological assay, volunteers will be asked to provide an additional blood sample of 20 
mL at 28 days after vaccination (Visit 4).   

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Clinically significant modifications in hematology will be assessed by medical judgment 
based on interpretation of deviations from institution’s normal values and 
recommendations from CBER FDA GUIDANCE FOR INDUSTRY: Toxicity Grading  
 
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  

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Confidential  
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Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials.  
Vaccination Procedure:  
All eligible subjects will receive one intramuscular vaccination (into the deltoid area of 
the non-dominant arm) with GVGH S. sonnei 1790GAHB vaccine containing  
25µg/dose. Subjects will be observed at the clinic site for 4 hours after vaccination.   
Procedure for Collection of Solicited AEs:  
Beginning in the evening following study vaccine administration (approximately 6 
hours), and daily during the following 6 days following vaccination, diary cards will be 
used to collect solicited local and systemic adverse events including other reactions (i.e. 
body temperature measurements and use of analgesics/antipyretics). A reminder phone 
call will be performed or an email will be sent by the site staff to the subject 2 and 6 days 
following vaccination to remind subjects that the diary card should be completed (no 
update on the status of the subject’s health will be solicited during these contacts that are 
not intended for safety data collection).   
Seven days following vaccination, a clinical visit (Visit 2) will be performed at the study 
site and all information recorded in the diary card will be reported on e-CRF in order to 
document all safety data occurred during the one week follow-up post vaccination.    
In addition to the solicited adverse events data, any unsolicited AE, solicited local and 
systemic AE that continue at 7 days after study vaccination (Visit 2), will be collected 
and recorded at V2, V3 and V4 by clinical study staff in the in the subject's source 
document. All Serious Adverse Events (SAEs), all AEs leading to vaccine/study 
withdrawal, all Adverse Events of Special Interest (AESI, see below) and all concomitant 
medications associated with those events, will be collected and recorded in the subject's 
source document and on an Adverse Events CRF(s) from the time of vaccination (visit 1) 
to study termination (visit 5). These data will be captured through interview of the subject 
and by review of available medical records.  

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Reactive arthritis and neutropenia will be collected and analyzed as AESIs for this study.  
A summary of the main medical and safety data to be collected into the e-CRF during the 
study is provided in Table 2.   
 

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Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  
Study Vaccines: GVGH S. sonnei (1790GAHB) vaccine  
The investigational agent is the GVGH S. sonnei 1790GAHB vaccine. The vaccine 
consists of S. sonnei OAg containing 1790-GMMA (approximately 200 µg/mL measured 
by protein content) adsorbed to Alhydrogel, (0.7 mg Al3+/mL) in Trisbuffered saline. The 
vaccine does not contain any preservative and is available in a liquid formulation as a 
single dose vials with 0.7 mL of injectable solution containing approximately 140 µg of 
GMMA (as protein content), adsorbed onto 0.49 mg Al3+.   
The vaccine will be used at a dose of 25 µg and will be obtained by bed-side mixing. 
Following dilution, the volume administered by intramuscular route will be 0.5 mL.   
Therefore, each 0.5 mL dose of GVGH S. sonnei 1790GAHB vaccine will contain  
3+. approximately 
25 μg of GMMA total protein and 0.35 mg of Al 

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Primary Endpoint(s):   
This study has no primary efficacy or safety endpoints.   
Primary Immunogenicity Endpoint(s)   
Memory response, against the OAg of S. sonnei will be evaluated by measuring IgG 
Geometric mean concentrations (GMCs) after vaccination as determined by ELISA with 
O-antigen containing LPS as coating antigen.  
Secondary safety endpoint(s):   
The measures of safety will include:  
a. Numbers of subjects with deviations from normal values of hematological tests 
after vaccination.  
b. Numbers of subjects with solicited local and systemic reactions during 7 days 
following vaccination. Solicited local reactions include injection site erythema, 
injection site induration and injection site pain; solicited systemic reactions include 
headache, arthralgia, chills, fatigue, malaise, myalgia, and fever (as measured 
orally).  
c. Numbers of subjects with reported unsolicited adverse events (of any nature and 
severity) during 84 days following vaccination.  
d. Number of subjects with reported SAEs throughout the study duration.  
 
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  

GSK  
Confidential  
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Secondary Immunogenicity Endpoint(s)  
a. IgG Geometric mean concentrations (GMCs) at 7, 14, 28 and 84 days after 
vaccination as determined by ELISA and applicable geometric mean ratios between 
post vaccination and baseline samples.  
b. Number and percentage of subjects with seroresponse for anti- LPS S. sonnei at 7, 
14, 28 and 84 days after vaccination. 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].  
c. Number and percentage of subjects with titers post vaccination concentration ≥ 121 
EU/ml for anti-LPS S. sonnei at 7, 14, 28 and 84 days after vaccination.  
A post-vaccination concentration ≥ 121 anti-LPS serum IgG units in the GVGH ELISA 
with O-antigen containing LPS as coating antigen corresponds to a titer of 1:800 in the 
ELISA method used by Cohen et al. (1989 J. Clin. Microbiol. 27:162). This antibody level 
is the median antibody concentration of a set of 87 convalescent subjects previously 
infected by S. sonnei. The value of 121 anti-LPS serum IgG units in the GVGH ELISA 
was determined by calibration against the Cohen ELISA (i.e., the GVGH standard serum 
was tested in Cohen’s lab using the Cohen’s methodology).  
The serologic assays on clinical samples will be performed at GSK, Clinical Laboratory 
Science (CLS), Marburg, Germany, or a delegated laboratory.  

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Exploratory Immunogenicity Endpoint(s):   
Other assays, including serum secretory IgA, might be done to further characterize the 
immune response to the study vaccine. The analysis will be described in the statistical 
analysis plan.   
Statistical Analyses:   
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  

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This Phase 1 safety and immunogenicity extension trial is aimed to descriptively evaluate 
the safety and immunogenicity profiles of the study vaccine, used either a booster (4th 
dose) or as a first dose. No specific hypotheses are tested in this trial. Descriptive analyses 
will be performed to describe and summarize the data (e.g. mean, median, min and max).  
Interim Analysis: No interim analysis is planned for this trial.  
Data Monitoring Committee:   
No ad hoc DSMB will be established for this trial as no interim assessment of safety data 
is anticipated.  
  

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Table 2 Time and Event Table- Treatment Period  
  
Visit Type  
Clinic Visit  
Clinic Visit  
Phone Call  
Clinic Visit  
Clinic Visit  
Clinic Visit  
Clinic Visit  
  
  
  
Study Day  
Visit  
Window  
(Days)  
Visit Number  
  
1  
3, 7  
V1+2 days;  
V1+6 days  
8  
V1+7 days  
15  
V1+14 days  
29  
V1+28 days  
85  
V1+84 days  
-21 to -1  
n/a  
n/a  
0 to -1  
0 to +4  
-3 to +4  
-3 to +7  
Screening  
1  
  
2  
3  
4  
5  
Study Event  
References  
  
  
  
  
  
  
  
Study Treatment  
  
  
  
  
  
  
  
  
Vaccination   
Section 5.2  
  
X  
  
  
  
  
  
Screening and Safety  
  
  
  
  
  
  
  
  
Informed Consent a  
Section 5.1.1  
X  
  
  
  
  
  
  
Medical History  
Sections 5.1.2  
X  
  
  
  
  
  
  
Physical Exam b  
Sections  
5.1.2  
and 5.1.3  
X  
X  
  
  
  
  
  
Symptom-directed 
Exam b   
physical  Section 5.3.1  
  
  
  
X  
X  
X  
X  

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Vital 
signs 
(temperature, 
respiratory rate, heart rate, blood 
systolic and diastolic pressure)  
Sections  
5.1.2  
Screening and 5.2.1  
Post-vaccination  
Procedures  
X  
X  
  
  
  
  
  
Safety blood draw (Hematology) 
c   
Sections 3.5  
and  
7.1.7  
X  
  
  
X  
  
  
X  
 
  
Visit Type  
Clinic Visit  
Clinic Visit  
Phone Call  
Clinic Visit  
Clinic Visit  
Clinic Visit  
Clinic Visit  
  
  
  
Study Day  
Visit  
Window  
(Days)  
Visit Number  
  
1  
3, 7  
V1+2 days;  
V1+6 days  
8  
V1+7 days  
15  
V1+14 days  
29  
V1+28 days  
85  
V1+84 days  
-21 to -1  
n/a  
n/a  
0 to -1  
0 to +4  
-3 to +4  
-3 to +7  
Screening  
1  
  
2  
3  
4  
5  
Study Event  
References  
  
  
  
  
  
  
  
Serology (HIV, hepatitis B and C, 
and HLA-B27 testing only  
for naïve subjects) d   
 Section  3.5  and  
5.1.2  
X  
  
  
  
  
  
  
Pregnancy Test  
 Sections  
3.5  
and 5.1.2  
  
X   
  
  
  
  
X  
Exclusion/Inclusion Criteria  
Section 4  
X  
  
  
  
  
  
  
Post Injection Assessment e  
Section 5.2.1  
  
X  
  
  
  
  
  
Subject Diary Dispensed with 
Training  
Section 5.2.1  
  
X  
  
  
  
  
  

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Subject Diary Reminder Call  
Section 5.2.2  
  
  
X  
  
  
  
  
Subject Diary Reviewed and 
Collected  
Section 5.3.1  
  
  
  
X  
  
  
  
Assess all AEs  
Section 7.1  
X  
X  
  
X  
X  
X  
  
Assess SAEs  
Section 7.1.4  
X  
X  
  
X  
X  
X  
X  
Assess for NOCDs, medically 
attended AEs, AEs leading to 
withdrawal, and AESIs  
Sections 
 
7.1.4.1  and 
7.1.3  
  
X  
  
X  
X  
X  
X   
 
 
  
Visit Type  Clinic Visit  
Clinic Visit  
Phone Call  
Clinic Visit  
Clinic Visit  
Clinic Visit  
Clinic Visit  
 
  
Study Day  
 
  
Visit (Days) 
 
Window  
 
  Visit 
Number  
  
1  
3, 7  
V1+2 days;  
V1+6 days  
8  
V1+7 days  
15  
V1+14 days  
29  
V1+28 days  
85  
V1+84 days  
-21 to -1  
n/a  
n/a  
0 to -1  
0 to +4  
-3 to +4  
-3 to +7  
Screening  
1  
  
2  
3  
4  
5  
Study Event  
References  
  
  
  
  
  
  
  
Assess relevant medications  
 Sections  
5.1.2  
and 6.5  
X  
X  
  
X  
X  
X  
X  
Immunogenicity  
  
  
  
  
  
  
  
  
Serology blood draw   
Section 3.5  
  
X  
  
X  
X  
X  
X  

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 Additional  blood  draw  for  
preparation of standard serum  
Section 3.5  
  
  
  
  
  
X  
  
Study Completion Procedures  
Study Termination f  
Section 5.5  
  
  
  
  
  
  
X  
  
Notes:  
a Informed Consent to be confirmed (oral confirmation) on Visit 1 prior to vaccination  
b Physical examination must be performed by a qualified health professional in accordance with local regulations and licensing requirements designated within the 
Site Responsibility Delegation Log.   
c In case of neutropenia, Complete Blood Count to be repeated on a weekly basis until resolution. If neutropenia occurs at the last study visit, Complete Blood Count 
to be repeated on a regular basis until resolution.  
d The serology tests that are performed at screening are HIV, hepatitis B and hepatitis C and they are conducted for subjects in the parent trial and for the naïve 
subjects. HLA-B27 testing is performed at screening only for the naïve subjects.   
e A post-injection local and systemic adverse event and body temperature and vital signs measurement will be performed approximately 30 minutes and 4 hours 
after vaccination. f Subjects who terminate the study early are recommended to complete certain study-related procedures. See protocol section 5.5 for further 
details.  
Table 3 Safety Tests Table  
HEMATOLOGY  
White Blood Cells (WBC)  
Red Blood Cells (RBC)  
Haemoglobin  
Haematocrit  
Platelets  
Eosinophils  
Basophils  

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Neutrophils  
Monocytes  
Lymphocytes  
Prothrombin time*  
  
SEROLOGY  
HIV antibodies*  
HbsAg*   
Hepatitis C antibodies*   
HLA-B27 testing**  
  
PREGNANCY TEST  
Human chorionic gonadotropin (hCG) in urine  
* Performed at screening only ** Performed at screening only for naïve subjects.  

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LIST OF ABBREVIATIONS  
AE  
 
Adverse Event  
AESI  
 
Adverse Events of Special Interest  
AP  
 
(Statistical) Analysis Plan  
ANC  
 
Absolute Neutrophil Count  
BMI  
 
Body mass index  
CBC  
 
Complete Blood Count  
CI  
 
Confidence Interval  
CLS  
 
Clinical Laboratory Science  
CRF  
 
Case Report Form  
CRO  
 
Contract Research Organization  
DM  
 
Data Management  
DSMB  
 
Data Safety Monitoring Board  
EC  
 
Ethics Committee  
eCRF  
 
Electronic Case Report Form  
EDC  
 
Electronic Data Capture  
ELISA  
 
Enzyme-linked Immunosorbent Assay  
EMA  
 
European Medicines Agency  
EU  
 
ELISA Unit  
FAS  
 
Full Analysis Set  
FDA  
 
Food and Drug Administration  
GCP  
 
Good Clinical Practices  
GMC  
 
Geometric Mean Concentration  
GMMA  
 
Generalized Modules for Membrane Antigens  
GMR  
 
Geometric Mean Ratio  
GMT  
 
Geometric Mean Titer  
GVGH  
 
GSK Vaccines Institute for Global Health  
HIV  
 
Human Immunodeficiency Virus  
IB  
 
Investigator’s Brochure  
ICF  
 
Informed Consent Form  
ICH  
 
International 
Conference 
on 
Harmonisation 
of 
Technical 
Requirements for Registration of Pharmaceuticals for Human Use  
IRB  
 
Institutional Review Board  
ITT  
 
Intention-To-Treat  
MSD  
 
Moderate to Severe Diarrhea  
LPS  
 
Lipopolysaccharide  
LSLV  
 
Last Subject Last Visit  
MedDRA  
 
Medical Dictionary for Regulatory Activities  
NOCD  
 
New onsets of chronic diseases  
OAg  
 
O antigen (of Shigella sonnei)  
pIMD  
 
Potential Immuno-Mediated Diseases   
PP  
 
Per Protocol  

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ReA  
 
Reactive arthritis  
SAE  
 
Serious Adverse Event  
SDA  
 
Source Data Agreement  
SDAF  
 
Source Documentation Agreement Form  
SOC  
 
System Organ Class  
SOP  
 
Standard Operating Procedure  
SPC  
 
Summary of Product Characteristics  
WHO  
 
World Health Organization  
  
  
  
  
  
  
  
 

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1.  
BACKGROUND AND RATIONALE  
1.1  
Background  
Shigellosis remains a major health problem in developing countries with approximately  
100 million cases per year mostly in children ≤5 years (Kotloff et al., 1999). Antibiotic 
resistance of Shigella is increasing and no vaccine is currently available against shigellosis.  
Livio et al showed that a quadrivalent vaccine containing S. sonnei and 3 
serotype/subserotypes of S. flexneri (S. flexneri 2a, S. flexneri 3a, and S. flexneri 6) can 
provide broad coverage against Shigella serotypes (up to 65%) (Livio et al., 2014), which 
cause shigellosis in the developing world, and can also provide broad coverage for travelers.   
In this view, GSK Vaccines Institute for Global Health (GVGH) developed the S. sonnei 
1790GAHB vaccine that has been tested in two Phase 1 trials in European adult population: 
one trial of the trials (protocol H03_01TP), looking at the intramuscular (IM) administration 
was conducted in France. In that study different antigen doses were evaluated and showed 
to be safe and well tolerated. More specifically, the trial evaluated the safety and 
immunogenicity profile of 5 different doses of GVGH Shigella sonnei 1790GAHB vaccine 
(1 µg to 100 µg) compared to placebo, when administered in 3 injections 1 month apart to 
50 healthy adults. The immunogenicity was evaluated at baseline, 28 days after each 
vaccination and at 168 days after third vaccination, by measuring the anti-LPS S. sonnei 
serum IgG. Overall, an antibody response was observed across all the vaccine groups. 
However, at most of the time points, the response was higher in subjects who received 
higher antigen doses (i.e., 25 µg, 50 µg, and 100 µg) than those who received lower doses 
(i.e., 1 µg and 5µg).   
More specifically, a vaccine dose of 25 µg was very well tolerated and induced median 
antibody concentrations above 121 EU/mL at all post vaccination time points. Since 121 
EU/mL is the median antibody titer in a panel of 87 convalescents previously exposed to  
S. sonnei infection and therefore protected against re-infection from the same serotype 
(Cohen et al, 1989), a vaccine dose of 25 µg has the potential to be protective when included 
in a vaccine against S. sonnei. After unblinding the immunogenicity database, it was 
observed that the trial subjects could be grouped in 2 groups based on S. sonnei antibody 
concentration at baseline, with 50% having undetectable and 50% having detectable anti-
LPS S. sonnei serum IgG antibody concentrations. Therefore, for a better understanding of 
the immunological response induced by the vaccine in naïve and primed subjects and for a 
better planning of new clinical studies, additional analyses were carried out. To mitigate 
the small size of study groups, subjects who received vaccines containing 1 µg and 5 µg 
antigen/dose were combined into a single group in which those with detectable antibody 
concentrations at baseline, showed median antibody concentrations slightly higher than 121 
EU/mL only at 1 month after the third vaccination. Same was done for subjects who 
received vaccines containing 25 µg, 50 µg, and 100 µg antigen/dose, among whom those 
with detectable antibody concentrations at baseline, showed, at all-time points (1 month 

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after the first, second and the third vaccinations and 6 months after the third vaccination), 
median antibody concentrations far higher than 121 EU/mL.   
Based on the results from this trial, it has been decided to proceed with further development 
using only the IM route of immunization and a dose of 25 µg was selected as the lowest 
dose that in phase 1 induced antibody titers comparable to antibodies in a population of 
convalescent subjects after natural infection already after the first vaccination.  
The results from H03_01TP suggest that 1790GAHB, even if administered at high doses, 
may not be sufficiently immunogenic in completely naïve adults (who might be a better 
predictor of antibody response in young naïve children, the ultimate target for this vaccine). 
Although the schedule of immunization used in the trial (i.e., 3 injections 1 month apart) 
may have not been optimal, it remains important to evaluate whether the vaccine was able 
to induce an immunological memory response.   
1.2  
Rationale  
The current H03_01E1TP study is designed to further characterize the immunogenicity 
profile of GVGH S. sonnei 1790GAHB vaccine and obtain useful information for further 
clinical development through the administration of a booster dose to individuals with 
undetectable antibodies at baseline in H03_01TP, approximately two to three years (i.e., 24 
to 36 months) after the third vaccine dose, compared to administration of 1 single vaccine 
dose to placebo recipients with undetectable antibodies at baseline in H03_01TP or to naïve 
subjects who were not part of H03_01TP study. The naïve subjects who were not part of 
H03_01TP study are added in order to have a more balanced number of previously 
unvaccinated and vaccinated subjects in the extension trial. In light of the safety and 
immunogenicity results of H03_01TP and of the potential development of a S. sonnei 
containing Shigella multivalent vaccine, a dose of 25 µg would be preferable for further 
development. Therefore, the use of this antigen dose is proposed for immunization of all 
subjects to provide further useful information for a more complete characterization of this 
vaccine strength.  
2.  
OBJECTIVES  
2.1  
Primary Objective(s)  
Primary Safety Objective(s)   
This study has no primary safety objective  
Primary Efficacy Objective(s)   
This study has no primary efficacy objective  
Primary Immunogenicity Objective(s)   

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To evaluate the memory response, as measured by anti-LPS S. sonnei serum IgG, 7 days 
after vaccination with a booster dose of GVGH S. sonnei 1790GAHB vaccine in individuals 
who had undetectable antibody titers at baseline in H03_01TP, approximately two to three 
years after the third vaccine dose, compared to administration of 1 single vaccine dose to 
placebo recipients with undetectable antibody titers at baseline in H03_01TP or naïve 
subjects who were not part of H03_01TP study.  
2.2  
Secondary Objective(s)  
Secondary Safety Objective(s)   
a. To evaluate the safety profile of one dose of GVGH S. sonnei 1790GAHB vaccine in 
subjects who previously received three vaccinations with 1790GAHB and in subjects 
receiving one dose 1790GAHB for the first time (either placebo recipients in 
H03_01TP or naïve subjects who were not part of H03_01TP study).  
b. To evaluate the safety profile of one dose of GVGH S. sonnei 1790GAHB vaccine in 
subjects receiving one dose 1790GAHB for the first time and having detectable 
antibodies at baseline of the extension trial. Secondary Efficacy Objective(s)   
This study has no secondary efficacy objectives.   
Secondary Immunogenicity Objective(s)   
a. To evaluate the immunogenicity profile 7, 14, 28 and 84 days after vaccination with 
one dose of GVGH S. sonnei 1790GAHB in subjects with undetectable antibody 
titers at baseline who previously received three vaccinations of 1790GAHB in 
H03_01TP and in placebo recipients with undetectable antibody titers at baseline in 
H03_01TP or naïve subjects who were not part of H03_01TP study.  
b. To evaluate the immunogenicity profile of one dose of GVGH S. sonnei 1790GAHB 
vaccine in subjects receiving one dose 1790GAHB for the first time and having 
detectable antibodies at baseline of the extension trial.  
c. To evaluate the persistence of anti-LPS S. sonnei serum IgG antibody titers 
approximately two to three years after the third vaccination with 1790GAHB.  
2.3  
Exploratory Objective(s)  
Other immunological assays might be performed to further characterize the immune 
response to the study vaccine including serum secretory IgA.  
 

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3.  
STUDY DESIGN  
3.1  
Overview of Study Design  
This is an open label, non-randomized, single center, Phase 1 clinical trial designed to 
further characterize the immunogenicity profile of GVGH S. sonnei 1790GAHB vaccine 
through the administration of a booster dose to individuals with undetectable antibodies at 
baseline in H03_01TP parent study, approximately two to three years (i.e., 24 to 36 months) 
after the third vaccine dose, compared to administration of 1 single vaccine dose to placebo 
recipients with undetectable antibodies at baseline in H03_01TP parent study  or to naïve 
subjects who were not part of H03_01TP study. The study includes a screening visit 
(performed at study Days -21 to -1), one clinical visit with vaccination (performed at study 
Day 1), 4 clinical visits (performed 7, 14, 28 and 84 days after vaccination), and 2 phone 
calls or email contacts (performed 2 and 6 days after the vaccination). No subject or study 
staff will be blinded for any study procedure.  
During the screening period, subjects giving informed consent will be screened for general 
health status. No pharmacokinetic tests will be performed as evaluation of pharmacokinetic 
properties is not required for vaccines unless new delivery systems are employed or when 
the vaccine contains novel adjuvants or excipients (Berlanda Scorza et al., 2012). Subjects 
who meet all inclusion criteria and none of the exclusion criteria, with screening tests within 
normal values and women of child bearing potential with negative urine pregnancy test at 
V1 will be eligible for enrollment. Female subjects of child bearing potential must use birth 
control measures during study participation.  
Up to 50 subjects will be enrolled into this trial. 24 subjects are eligible from the parent 
H03_01TP trial. With respect to naïve subjects who were not part of H03_01TP study, 
considering that in the original H03_01TP population 50% of subjects did not have 
detectable antibodies at baseline, with 26 subjects, it is anticipated that at least 13 subjects 
should not have detectable antibodies. This number combined with that of placebo 
recipients in H03_01TP should be sufficient to allow a balanced contribution of previously 
unvaccinated and vaccinated subjects in the extension trial. Subjects withdrawn or lost to 
follow up will not be replaced. The sample size is not driven by any statistical hypothesis, 
but by availability of subjects from H03_01TP study and fulfilling inclusion criteria. 
Subjects will be recruited as detailed in table 1.  
No randomization will be required since all subjects will receive the same dose of the same 
vaccine.  
Screening/baseline clinical safety labs will take place before Visit 1 (from -21 up to -1 day). 
All subjects providing informed consent will undergo review of medical history, a complete 
physical examination including vital signs measurement (temperature, respiratory rate, 
heart rate, blood systolic and diastolic pressure) at the screening visit (study Day -21 to -1) 
and at visit 1 (Day 1) for evaluation of the general health status by clinical assessment and 
verification of inclusion and exclusion criteria. At clinic visit 2 and at subsequent visits, a 

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brief symptom-directed physical examination (if necessary according to symptoms the 
subject has reported) will be performed.   
A blood sample will be obtained as part of the initial screening for hematology and serology 
(HIV, hepatitis B and C, and for HLA-B27 testing only for naïve subjects). Blood will be 
collected for hematology also on day 8 and 85 (visit 2 and 5 respectively). Each consented 
subject will have blood collected before vaccination on day 1 for baseline immunological 
testing and on day 8, 15, 29 and 85 (visit 2, 3, 4, and 5 respectively) post vaccination for 
immunological. Additional blood draw for preparation of standard serum will be done on 
day 29 post vaccination (visit 4). Urine pregnancy test will be done at visit 1 prior to 
vaccination and at visit 5. All individuals with neutropenia occurring at any time during the 
study will have additional blood draws to repeat complete blood count on a weekly basis 
until the neutropenia resolves. If neutropenia occurs at the last study visit, Complete Blood 
Count to be repeated on a regular basis until resolution (for classification of neutropenia 
during the trial, refer to Section 3.8, Procedures Related to Neutropenia).  
Subjects will be observed at the clinic for 4 hour after vaccination on visit 1. Vital signs 
will be collected before vaccination and at 30 minutes and 4 hours post vaccination. Before 
leaving the clinic,  they will be given a paper dairy card and trained to record in any adverse 
events occurring before visit 2 and will be reminded by phone call or email on day 3 and 7 
post vaccination. These dairy cards will be collected and reviewed on day 8 post vaccination 
(visit 2).  
Any unsolicited AE until visit 4, SAEs until study termination, all AEs leading to study 
withdrawal, reactive arthritis and severe neutropenia (AESI) and all concomitant 
medications associated with those events, will be collected and recorded in the subject’s 
source document and in the eCRF. Further details on study procedure are found in sections 
5, Study Procedures and 7, Assessments.  
3.2  
Study Period  
Each subject should expect to participate in the study for 85 days, from the time of 
enrolment through the last study visit.  
3.3  
Blinding Procedures  
No blinding procedures will be applied for this study.  
3.4  
Data Collection  
3.4.1  Data Collected from Subjects  
The following data will be collected from each subject over the duration of their study 
participation:  
• 
Demographic Information  

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• 
Medical History  
• 
Post-vaccination immediate reactions  
• 
Vital signs including but not limited to body temperature  
• 
Adverse Events  
• 
Concomitant Medications  
All data collected must only be identified using the GSK Subject ID and Subject code, as 
described in section 5.1.4, Randomization.  
3.4.2  Tools Used for Data Collection  
Subject Diary  
Paper Diaries, hereafter referred to as Subject Diaries will be the only source document 
allowed for solicited local and systemic adverse events (including body temperature 
measurements), starting approximately 6 hours post-vaccination and collected by the 
subject. The following additional rules apply to documentation of safety information 
collected in the Subject Diary.  
The Investigator or delegated staff should monitor the Subject’s Diary status throughout the 
study for compliance and any solicited local and systemic adverse events that were of 
concern to the subject.  
1. No corrections or additions to the information recorded by the subject within the Subject 
Diary will be allowed after it is delivered to the site.  
2. Any blank or illegible fields on the Subject Diary must be described as missing in the 
CRF.  
Case Report Forms  
An electronic data capture (EDC) system (e.g., Inform™) will be used to expedite the entry 
of data. A qualified site staff member(s) will enter data in English into the web enable EDC 
system in a timely manner; the data will be stored in GSK clinical database management 
system. eCRF data will be reviewed routinely by GSK Data Management (DM) Group and 
GSK clinical monitors or representatives.  
The information from the diary will be entered in the eCRF at visit 2. All data not recorded 
directly on the eCRFs must be verified by checking eCRF entries against source documents 
in order to ensure that the data have been completely and accurately reported as required 
by the study protocol.  
Source data verification will be performed and recorded following GSK internal SOP. The 
subject must also allow access to his/her medical records. Each subject will be informed of 
this prior to the start of the study.  

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The following additional rules apply to documentation of Subject Diary information 
collected in the CRFs:  
1. The site must enter all readable entries from the Subject Diary into the eCRF, including 
those values that may be biologically implausible (e.g. body temperature: 400°C).  
2. Any illegible or implausible data should be reviewed with the subject. If an underlying 
solicited or unsolicited adverse event is described on review with the subject, this 
should be described in the source document and reported as an unsolicited adverse event 
in the Adverse Event CRF (e.g., if the subject above confirms body temperature of 40°C 
on the day in which body temperature: 400°C was written into his/her Subject Diary, 
this fever of 40°C should be recorded in the Adverse Event CRF).  
3. Any newly described safety information (including a solicited adverse event) must not 
be written into the Subject Diary and must be described in the study file (studyspecific 
workbook) as a verbally reported adverse event. Any adverse event reported in this 
fashion must be described as an unsolicited adverse event and therefore entered on the 
Adverse Event CRF.  
3.5  
Collection of Clinical Specimens  
Collected samples will be used for protocol mandated research and purposes related to the 
improvement, development and quality assurance of the laboratory tests described in this 
protocol. This may include the management of the quality of these tests, the maintenance 
or improvement of these tests, the development of new test methods, as well as making sure 
that new tests are comparable to previous methods and work reliably.  
It is also possible that future findings may make it desirable to use the samples acquired in 
this study for future research, not described in this protocol. Therefore, all subjects in 
countries where this is allowed/all subjects will be asked to give a specific consent to allow 
the Sponsor or a contracted partner to use the samples for future research. Future research 
will be subject to the laws and regulations in France and will only be performed once an 
independent Ethics Committee or Review Board has approved this research. Information 
on further investigations and their rationale can be obtained from GSK.   
Any sample testing will be done in line with the consent of the individual subject If 
additional testing is performed, the marker priority ranking given in the table below may 
be changed.  
Table 4 Blood For Immunological purposes  
Blood sampling timepoint  
Subset 
/Subcohort 
Name   
No. subjects  Component  
Components  
priority  
rank 
  
Type of contact and 
timepoint  
Sampling 
timepoint  
  
Screening (Day -21 to 1) 
Pre-Vacc  
All subjects  
50  
HIV*  
NA  
All subjects  
50  
anti-HBsAg*  
All subjects  
50  
Hepatitis C*   

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Naïve subjects  26  
HLA-B27  
Visit 1 (Day 1)  
Pre-Vacc  
  
50  
Anti LPS IgG 
ELISA  
NA  
Visit 2 (Day 8)  
Post-Vacc 1    
50  
Anti LPS IgG 
ELISA  
NA  
Visit 3 (Day 15)  
Post-Vacc 2    
50  
Anti LPS IgG  NA  
Visit 4 (Day 29)  
Post-Vacc 3    
50  
Anti LPS IgG  1  
Standard 
Serum  
TBD  
TBD  
Standard pool 
for ELISA  
2  
Visit 5 (Day 85)  
Post-Vacc 4    
50  
Anti LPS IgG  NA  
* The results of this testing might potentially impact the subject medical care   
Processing of each specimen should be completed by a qualified site member and in 
accordance with the study-specific laboratory manual. Testing of clinical specimens will be 
performed by GSK Clinical Laboratory Science (CLS), Marburg, (Germany) or a delegated 
laboratory. Refer to the study-specific laboratory manual for additional details.   
Blood Specimens  
Approximately 15 mL blood draw will be obtained for hematological and serological (HIV, 
hepatitis B and C for subjects who were in the parent study. Naïve subjects will however 
have 25mL of blood drawn for HLA-B27 testing in addition of the hematological and 
serological (HIV, hepatitis B and C) tests as part of the initial screening. One additional 
blood draw of 6 mL for hematological tests will be obtained at 8 days (Visit 2) and 85 days 
(Visit 5) after vaccination (see Table 2). Each subject will have 20 mL of blood drawn for 
immunological studies before vaccination at Day 1 and 8, 15, 29 and 85 days after 
vaccination. For the purpose of creating a standard reference serum for the serological 
assay, study subjects will provide an additional blood sample of 20 ml at 29 days after 
vaccination.  
All individuals with neutropenia occurring at any time during the study will have additional 
6mL blood draws to repeat complete blood count on a weekly basis until the neutropenia 
resolves.  
Clinically significant modifications in hematology will be assessed by medical judgment 
based on interpretation of deviations from institution’s normal values and recommendations 
from CBER FDA GUIDANCE FOR INDUSTRY: Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.  
The total amount of blood collected over the study period per subject will be approximately 
157 mL including screening for HLA for a subject who was not part of the parent study and 
the additional blood sample at day 29 for the standard pool serum for immunogenicity and 
excluding possible repeats of hematological tests in case of neutropenia.  

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Serum samples will be stored frozen below -20ºC. The sera aliquots will be shipped 
according to guidelines provided by GSK to the laboratories for analysis. The serologic 
assays will be conducted at the GSK Clinical Laboratory Science, Marburg, (Germany) or 
a delegated laboratory.  
Aliquots of sera will be archived for 20 years at the GSK laboratory in Marburg (Germany) 
for future research on immunogenicity of the Shigella vaccines. Study-related future 
research may include additional evaluation of immunogenicity on Shigella sonnei (i.e. IgM, 
IgA against the O antigen or IgG against other antigens of Shigella sonnei). It may not be 
possible to contact individual participants in the future in order to disseminate results 
obtained from research conducted on archived samples. However, these results, if relevant, 
will be published in peer-reviewed journals and disseminated to the scientific community. 
An archival time of 20 years should cover the entire vaccine development time, including 
the possibility to address potential questions from regulators during the registration time.  
Complete instructions for processing, labeling, storage and shipping of samples are 
included in the Clinical Specimen Laboratory Manual provided to the investigators and 
available in the Investigator Site File.  
Blood samples must be collected in the appropriate manner, using exclusively materials and 
guidelines supplied by GSK. The investigator must ensure that his/her personnel and the 
laboratory(ies) under his/her supervision comply with this requirement. The results of 
safety testing will be recorded in the source document and eCRF.  
Urine Specimens  
In this study urine samples will be collected from women of childbearing potential only 
for pregnancy testing before vaccination at Day 1 (visit1) and at study termination (visit 
5).  
3.6  
Stopping/Pausing Guidelines  
There are no predetermined stopping rules in this study. Subjects may be withdrawn from 
the study according to investigator discretion as described in section 3.8, Premature 
Withdrawal from Study.  
There are no predetermined stopping rules other than circumstances for which subjects may 
be withdrawn from the study according to the best interests of the subject as described in 
section 3.8, Premature Withdrawal from Study.  
3.7  
Data Monitoring Committee  
No Data Monitoring Committee will be established for this study.  

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3.8  
Premature Withdrawal from Study  
Subjects may withdraw at any time, or be dropped from the study at the discretion of the 
investigator should any untoward effects occur and/or for safety reasons. In addition, a 
subject may be withdrawn by the investigator or Sponsor if he/she violates the study plan 
or for administrative reasons. The investigator or study coordinator must notify the Sponsor 
immediately when a subject has been withdrawn due to an adverse event.  
The circumstances above are referred to as premature withdrawal from the study, and the 
reason for premature withdrawal should be clearly documented and detailed in the source 
documentation. The investigator should make every attempt to evaluate the subject’s safety, 
including resolution of ongoing AEs, at the time of premature withdrawal. If a subject wants 
to withdraw from the study prior to the last planned study visit, the subject will be asked to 
be followed for safety for the duration of the study. When a subject withdraws, or is 
withdrawn, from the study, the procedures described in section 5.5.1, Early Termination 
Visit should be completed if possible.  
The reasons for premature withdrawal from the study include: Adverse event, death, 
withdrawal of consent, lost to follow-up, administrative reason, and protocol deviation. 
These reasons are described in greater detail below.  
Adverse Event  
For any subject withdrawn from study participation prior to the planned Study Termination 
Visit, it is important to determine if an AE was associated with the reason for discontinuing 
the study. This AE must be identified on the AE CRF page by indicating “Withdrawn from 
study due to AE”. Any ongoing AEs at the time of study withdrawal must be followed until 
resolution or stabilization.  
Death  
For any subject withdrawn from study participation due to death, this should be noted on 
the Study Termination CRF page and the associated SAE that led to the death must be 
reported.  
Withdrawal of consent  
The subject can withdraw consent for participation in the study at any time without penalty 
or loss of benefit to which the subject is otherwise entitled. Reason for early termination 
should be deemed as “withdrawal of consent” if the subject withdraws from participation 
due to a non-medical reason (i.e., reason other than AE). If the subject intends to withdraw 
consent from the study, the investigator should clarify if the subject will withdraw 
completely from the study or if the subject will continue study participation for safety, or a 
subset of other study procedures. If the subject requests complete withdrawal from the 
study, no further study interventions will be performed with the subject.  

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Lost to Follow-Up  
For subjects who fail to show up for final visits (clinic or telephone contacts), or for three 
consecutive visits, study staff are encouraged to make at least three documented attempts 
to contact the subject by telephone and at least one documented written attempt to contact 
the subject to encourage the completion of study termination procedures. These efforts to 
contact the subject should be recorded in the source document. The termination date for the 
subject to be captured on the Study Termination CRF page is the date of the last successful 
contact (clinic visit or telephone) with the subject.  
Administrative Reason  
Examples for subjects withdrawn from the study due to administrative reason can include: 
Sponsor decision to terminate the study, subject meeting a pre-specified withdrawal 
criterion, subject discontinuation for insurance issues, moving, no time, etc. This reason 
should be noted in the Study Termination CRF page and any ongoing AEs at the time of 
study withdrawal must be followed until resolution/stabilization.  
If the clinical study is prematurely terminated by the Sponsor, the investigator is to promptly 
inform the study subjects and local EC/IRB and should assure appropriate therapy and 
follow up for the subjects. All procedures and requirements pertaining to the archiving of 
study documents should be followed. All other study materials (study medication/vaccines, 
etc.) must be returned to the Sponsor.  
For subjects who are withdrawn from the study due to receipt of an excluded 
medication/vaccination or due to significant protocol non-compliance, this reason should 
be noted in the Study Termination CRF page.  
Subjects should submit the diary card data at day 8 (visit 2). Subject must be contacted by 
phone if they fail to submit the diary card on visit 2 and proper arrangement be made for 
collection of dairy.  
Protocol Deviation  
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. In general, subjects associated with protocol deviations may 
remain in the study unless continuation in the study jeopardizes the subject’s health, safety, 
or rights.  
Investigators will apply due diligence to avoid protocol deviations. Under no circumstances 
should the investigator contact GSK or its agents, if any, monitoring the study to request 
approval of a protocol deviation, as no authorized deviations are permitted. If the 
investigator feels a change to the protocol would improve the conduct of the study this must 
be considered a protocol amendment, and unless such an amendment is agreed upon by 

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GVGH and a substantial amendment is approved by the IRB/EC and health authorities it 
cannot be implemented.   
Any subject who becomes pregnant during the study, despite the protocol requirement for 
adequate contraception, should be encouraged to continue participating in the study for 
safety follow-up. The site must complete a Pregnancy Report CRF (initial report) as soon 
as possible after learning of pregnancy occurrence (see section 7.1.6, Pregnancies for 
further details). If the subject withdraws from the study for any of the above categories 
except death, the site will obtain permission from the subject to continue to remain in 
contact with her until the outcome of the pregnancy is known, even if the outcome is not 
known until after the subject reaches the end of follow-up period.  
3.9  
End of Study  
Evaluation of the primary and/or secondary immunogenicity objectives requires the testing 
of biological samples from the study subjects, which can only be completed after all 
samples are collected. The last samples for the analysis of the primary and/or secondary 
objectives will be taken at visit 5.   
For the purpose of this protocol, end of study (EoS) is defined as the completion of the 
testing of such biological samples, to be achieved no later than 8 months after collection of 
the last biological sample visit.  
4.  
SELECTION OF STUDY POPULATION  
4.1  
Inclusion Criteria  
In order to participate in this study, all subjects must meet ALL of the inclusion criteria 
described. Are included:  
1. 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.  
2. 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.  
3. Individuals in good health as determined by the outcome of medical history, physical 
examination, hematological blood tests and clinical judgment of the investigator.  
4. 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.   
5. Individuals affiliated to a social security regimen.  
  

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4.2  
Exclusion Criteria  
Are excluded:  
1. 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.    
2. Individuals with any progressive or severe neurological disorder, seizure disorder or 
Guillain-Barré syndrome.  
3. Individuals who are not able to understand and to follow all required study procedures 
for the whole period of the study.  
4. 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.  
5. Progressive, unstable or uncontrolled clinical conditions.  
6. Hypersensitivity, including allergy, to any component of vaccines, medicinal products 
or medical equipment whose use is foreseen in this study.  
7. Individuals with a known bleeding diathesis, or any condition that may be associated 
with a prolonged bleeding time.  
8. Clinical conditions representing a contraindication to intramuscular vaccination and 
blood draws.  
9. Abnormal function of the immune system resulting from:  
• 
Clinical conditions;  
• 
Systemic administration of corticosteroids (PO/IV/IM) 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.   
10. Received immunoglobulins or any blood products within 180 days prior to informed 
consent.  
11. Study personnel as an immediate family or household member.  
12. 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.  
13. 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.  

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14. 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.  
15. Individuals who have received blood, blood products, and/or plasma derivatives 
including parenteral immunoglobulin preparations in the past 12 weeks.  
16. Individuals with body temperature > 38.0 degrees Celsius within 3 days of intended 
study vaccination.   
17. Individuals with Body Mass Index (BMI)> 30 kg/m2.  
18. Individuals with history of substance or alcohol abuse within the past 2 years.   
19. 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.  
20. Females with history of stillbirth, neonatal loss, or previous infant with anomaly.  
21. Individuals who have a previously laboratory confirmed or suspected disease caused by 
S. sonnei.  
22. Individuals who have had household contact with/and or intimate exposure to an 
individual with laboratory confirmed S. sonnei.  
23. 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.  
24. Individuals with a neutrophil count value lower than 1.8 109/L at screening assessment.  
25. Individuals with human leukocyte antigen (HLA)-B27 positive and/or with history of 
reactive arthritis.  
26. Previous history of Benign Ethnic Neutropenia or drug related Neutropenia and/or 
concomitant treatment with neutropenic agents.  
  
4.3  
Criteria for Delay of Vaccination  
There may be instances when individuals meet all eligibility criteria for vaccination yet 
have a transient clinical circumstance which may warrant delay of vaccination: body 
temperature elevation (≥ 38.0 °C within 3 days prior to intended study vaccination), or use 
of antipyretics and/or analgesic medications within 24 hours prior to vaccination. Under 
such circumstances, a subject may be considered eligible for study enrolment after the 
appropriate window for delay has passed and inclusion/exclusion criteria have been 
rechecked, and if the subject is confirmed to be eligible.  
 

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5.  
STUDY PROCEDURES  
The sections that follow provide an overview of the procedures that are to be followed in 
enrolling, evaluating, and following subjects who participate in this clinical study. Visits 
can be either clinic visits or safety follow-up telephone calls, as specified in the Table below 
and in the Time and Events Table 2.  
Table 5 Study Procedures  
Visit Category  
Procedures  
Pre-vaccination Clinic Visit(s)  
Section 5.1 describes procedures to be followed prior 
to study vaccination: informed consent, screening, 
enrolment, and randomization  
Vaccination Clinic Visit(s)  
Section 5.2 describes procedures to be followed 
during each clinic visit involving vaccination: 
vaccination, 
post-vaccination 
procedures, 
and 
postvaccination reminders   
Post-vaccination Visit(s)   
Section 5.3 describes follow-up clinic visits and 
safety follow-up calls  
Unscheduled Visit(s)  
Section 5.4 describes possible procedures to be 
followed at unscheduled clinic visit  
Study Termination Visit  
Section 5.5 describes procedures to be followed at the 
last study visit for a subject (may include early 
termination visit)  
  
5.1  
Pre-vaccination Clinic Visit(s)  
This section describes the procedures that must be performed for each potential subject 
prior to vaccination, including obtaining informed consent, screening, enrolment and 
randomization.  
5.1.1  Informed Consent/Assent  
"Informed consent" is the voluntary agreement of an individual or his/her legal guardian(s) 
to participate in research. Consent must be given with free will of choice, and without undue 
inducement. The individual must have sufficient knowledge and understanding of the 
nature of the proposed research, the anticipated risks and potential benefits, and the 
requirements of the research to be able to make an informed decision.  
Informed consent following local IRB/EC guidance must be obtained before conducting 
any study-specific procedure (i.e., all of the procedures described in the protocol). The 
process of obtaining informed consent should be documented in the subject source 
document in addition to maintaining a copy of the signed and dated informed consent. 
Additional specifics regarding the informed consent processes are located in section 13.2, 
Informed Consent Procedures.  

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5.1.2  Screening  
Subject identification numbers will be assigned sequentially to the subjects who have 
consented to participate in the study. The eligibility of the subject will be determined based 
on the inclusion and exclusion criteria listed in section 4, Selection of Study Population and 
evaluated during this screening procedure.  
Prior to study enrolment, demographic data will be collected from the subject, including: 
age, gender, race and body mass index.  
Medical history will also be collected, including but not limited to any medical history that 
may be relevant to subject eligibility for study participation such as prior vaccinations, 
concomitant medications, and previous and ongoing illnesses or injuries. Subject who 
participated in the H03_01TP parent trial will have their medical history since the last visit 
reviewed. Relevant medical history can also include any medical history that contributes to 
the understanding of an adverse event that occurs during study participation, if it represents 
an exacerbation of an underlying disease/pre-existing problem.  
Review of systems is a structured interview that queries the subject as to any complaints 
the subject has experienced across each organ system. This will be performed before 
enrolment and used to guide physical examination.  
Important prior and concomitant medications or vaccinations taken prior to start of study 
should be collected (refer to section 6.5, Prior and Concomitant Medications and Vaccines 
for further details).  
Vital signs: heart rate, respiratory rate, diastolic and systolic blood pressure, temperature 
and also anthropometric measurements: height and weight will be collected  
A general physical examination is to be performed by a qualified health care practitioner. 
“Qualified health care practitioner” refers to any licensed health care professional who is 
permitted by institutional policy to perform physical examinations and who is identified 
within the Study Staff Signature Log.  
These data will be written in the source document (see section 9.1, Source Documentation).  
Approximately 15 mL of blood will be obtained as part of the initial screening for 
hematology and serology testing (HIV, hepatitis B and C) and 25 mL for the same tests and 
HLA-B27 for naïve subjects. Another 20 mL of blood will be collected before vaccination 
on day 1 for baseline immunological testing (Refer to section 3.5, Collection of Clinical 
Specimens).  
In the event that the individual is determined ineligible for study participation, he/she is 
considered a screen failure. The reason for screen failure must be documented in the 

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Screening and Enrolment log. If the individual is determined to be eligible for the study, 
he/she will be enrolled into the study.  
5.1.3  Enrolment  
After signing the informed form, if an individual is determined to be eligible for study 
participation, the investigator will enroll the subject.   
5.1.4  Randomization  
5.1.4.1 Randomization  
This is a non-randomized study which is an extension of H03_01TP study done on the same 
setting. Enrolled subjects will be manually assigned a unique Subject ID; since 24 subjects 
to be enrolled are from the previous study (H03_01TP) database, so these will preserve 
their subject ID if they get enrolled. The subsequent 26 new recruits as explained on section 
3.1 overview of study design will be assigned subject ID following the same order used in 
H03_01TP but starting from where last subject’s ID ended. This will easier identify subjects 
who are on booster vaccine dose from subjects given one vaccine dose as per this study. 
The Subject ID will be the subject’s unique identification number for all CRFs and 
associated study documentation that will be used for duration of the study. The Screening 
Number ceases to be used and remains in the Screening and Enrolment Log.   
If for any reason, after enrolment the subject fails to undergo treatment/study procedures 
this is an Early Termination and the reason should be recorded in source document as 
specified in the Source Documentation Agreement Form (SDAF). The information on these 
Early Termination subjects should be kept distinct in the source documentation from 
subjects who are screen failures, as described in section 5.1.2, Screening.  
5.2  
Vaccination Clinic Visit(s)  
The vaccination will be performed on study day 1.  
Ensure all serology samples are taken prior to vaccination.  
Perform pregnancy testing in women of childbearing age (section 3.5, Collection of Clinical 
Specimens for guidance regarding the procedure). Informed consent process with any 
women of childbearing potential will include counseling about pregnancy including 
discussion of their commitment to practice acceptable birth control measures (defined as 
oral, injected or implantable contraceptives).Women of childbearing potential are defined 
as a post onset of menarche and pre-menopausal female capable of becoming pregnant. 
This does not include females who meet any of the following conditions: (1) menopause at 
least 2 years earlier, (2) tubal ligation at least 1 year earlier, (3) total hysterectomy or (4) 
post bilateral oophorectomy.     

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After completing the pre-vaccination procedures on day 1, administer the vaccine to the 
subject according to the procedures described in section 6.3, Vaccine Preparation and 
Administration.  
Prior to administration of vaccination, confirm that the subject is eligible for study 
vaccinations 
by 
checking 
his/her 
medical 
history, 
clinical 
examination, 
all 
inclusion/exclusion criteria and that the subject does not meet any criteria for delaying study 
vaccinations as described in section 4, Selection of Study Population  
5.2.1  Post-vaccination Procedures  
The following post-vaccination procedures will be performed on day 1:   
After vaccination, the subject will be observed for at least 4 hour including observation for 
unsolicited adverse events, solicited adverse events, and body temperature and vital signs 
measurement. Record all safety data collected during this time in the subject’s source 
document.  
A Subject Diary will be used in this study to document solicited adverse events. The Subject 
Diary is the only source for collection of these data; therefore, it is critical that the subject 
completes the Subject Diary correctly. The subject should be trained on how and when to 
complete each field of the Subject Diary.  
Subject Diary training should be directed at the individual(s) who will perform the 
measurements of adverse events and who will enter the information into the Subject Diary.  
The same individual should complete the Subject Diary throughout the 7 days following 
vaccination.  
Training of the subject on how to measure an injection site reaction should be performed 
while the subject is under observation after vaccination. The subject must understand that 
timely completion of the diary card on a daily basis is a critical component to study 
participation. The subject should also be instructed to write clearly and to complete the 
diary card in pen. Any corrections to the diary card that are performed by the person 
completing the diary card should include a single strikethrough line with a brief explanation 
for any change. No changes can be made to the diary card when it is returned to the clinic.  
Starting on the day of vaccination, the subject will check in the evening for specific types 
of reactions at the injection site (solicited local reactions), any specific generalized 
symptoms (solicited systemic reactions), body temperature (taken preferably orally) any 
other symptoms or change in the subject’s health status, and any medications taken 
(excluding vitamins and minerals).   

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The subject should be trained on how to self-measure local solicited adverse events and 
body temperature. The measurement of solicited local adverse events is to be performed 
using the ruler provided by the site.  
Body temperature measurement is to be performed using the thermometer provided by the 
site. If the subject feels unusually hot or cold during the day, the subject should check body 
temperature. If the subject has fever, the highest body temperature observed that day should 
be recorded on the Diary Card. The collection of body temperature, solicited local adverse 
events, solicited systemic adverse events will continue for a total of 7 days on the Diary 
Card. The collection of unsolicited adverse events and medications will continue after the 
7 days on the Diary Card.  
At the end of the observation period, the site should schedule the next study visit with the 
subject. The subject will receive a study ID card to be used as a written reminder of the next 
planned study activity and to provide study staff contact details. The subject will be 
reminded to complete the Diary card daily and to contact the site if there are any questions 
and to contact the site immediately (or as soon as the subject is medically stable) if the 
subject has a medical condition that leads to a hospitalization or an emergency room visit.  
All subjects presenting with a history of fever or any other sign or symptom judged by the 
investigator to be as a result of an infection within 21 days of vaccination will have a blood 
sample collected for a complete blood count to establish the absolute neutrophil count. If 
there is a neutropenia, the subject will be managed appropriately according to local and 
international requirements.   
5.2.2  Post-vaccination Reminders  
Reminder calls (or emails) are not intended to be an interview for collection of safety data. 
If the subject wishes to describe safety information, this information should only be 
collected by a healthcare professional at the site, and the safety data described must be 
written down in the subject’s medical chart/source document.  
Subject Diary Reminder Calls / Emails  
Subject Diary reminder calls will be performed or email will be sent on day 3 and day 7 
post vaccination. The purpose of this call or email is to remind the subject about completion 
of the Subject Diary. The call/email follow the Subject Diary Reminder Telephone 
Call/Email Scripts provided to the site. The subject should be reminded to contact the site 
via the telephone number provided in the informed consent to discuss medical questions. 
The safety data described by the subject on a telephone call must be written down in source 
documents and the subject should be reminded to write the information down in the diary 
card.  
If the email is printed by study staff to document that the reminder was sent, all personal 
information such as name and email address of the subject, will be removed before printing.  

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5.3  
Post-vaccination Visit(s)  
5.3.1  Follow-up Clinic Visit(s)  
Safety follow-up clinic visits will be performed on day 8, day 15, day 29 and day 85.  
During visit 2, the Subject Diary will be reviewed. No changes to the information recorded 
within the Subject Diary are permissible. For details on the Subject Diary see sections 3.4.2, 
Tools Used for Data Collection and 5.2.1, Post-vaccination Procedures. The subject will be 
interviewed to determine if any unsolicited adverse events occurred and if any concomitant 
medications or vaccines were taken or received in the time since the last visit. This 
interview will follow a checklist which will facilitate the collection of relevant safety 
information. The healthcare professional reviewing these data will discuss the symptoms 
(if any) reported by the subject and will determine if any additional diagnoses and/or 
adverse events are present. Adverse events reported by the subject at this follow-up clinic 
visit must be recorded in the subject's source document and on an Adverse Events eCRF, 
as specified in section 7.1, Safety Assessment, and not written on the checklist used for the 
interview.  
Perform a brief symptom-directed physical examination if necessary according to 
symptoms the subject has reported. This is a physical examination that will include an 
examination of organ systems that are relevant to the investigator based on review of the 
subject’s reported adverse events, concomitant medication use. The physical assessment 
must be performed by the investigator or designee of the investigator, who is qualified to 
perform a physical assessment in accordance with their institutional policy. Corresponding 
information is documented in the subject’s source document.  
The site should schedule the next study activity, i.e. the next clinic visit and reminder phone 
call/email with the subject. The subject will be reminded to contact the site if there are any 
questions and to contact the site immediately (or as soon as the subject is medically stable) 
if the subject has a medical condition that leads to a hospitalization or an emergency room 
visit.  
5.3.2  Safety Follow-up Calls  
No safety follow up call will be made in this study.  
5.4  
Unscheduled Visits  
An unscheduled visit describes a non-routine study visit triggered by a specific event. These 
could include anticipated or unanticipated adverse events or interventions.  Data obtained 
from such unscheduled visit should be record in a respective source document and eCRF. 
If a case of neutropenia is observed after vaccination and still prevalent on a subsequent 
visit, the results will be recorded in the Unscheduled Lab eCRF.   

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All individuals with a neutropenia, occurring at any time during the study, will have 
additional blood draws for complete blood count to be repeated on a weekly basis until the 
neutropenia resolves. If neutropenia occurs at the subject’s last study visit, the complete 
blood count will be repeated on a regular basis until resolution. For classification of 
neutropenia during the trial, refer to section 7.1.4.1 Adverse Events of Special Interest.  
5.5  
Study Termination Visit  
The study termination visit will occur on day 85 (visit 5). The date of termination is the date 
of the last contact (clinic visit or telephone call) in which the subject’s health status was 
assessed or, in cases where the subject does not agree to any further safety follow-up; it is 
the date consent is withdrawn. This date should be recorded on the termination eCRF page. 
For visit procedures to be performed for a subject whose planned study participation ends 
prematurely, please see section 5.5.1, Early Termination Visit.  
At the clinic visit or during the telephone call, the following procedures will be performed:   
Review of systems, interview of subject to collect: medically attended adverse events, AEs 
leading to withdrawal, SAEs, AESIs, and new onset of chronic disease, interview of subject 
to collect concomitant medications in relation to these events, vaccinations, symptom-
directed physical assessment and a check of general appearance, blood sampling for safety 
laboratory assessment (hematology testing) and immunogenicity, and a urine pregnancy 
test for women of childbearing potential.  
The site will review with the subject the plan of when information relating to the subject’s 
participation in the study may be available (i.e., study results, treatment assignments).  
The site will complete the termination eCRF page and this will mark the completion of the 
subject’s participation in the study.  
5.5.1  Early Termination Visit  
When a subject is withdrawn from treatment or withdraws from the study, the investigator 
will notify the Sponsor and, when possible, will perform the procedures listed below. The 
reason(s) for the early termination will be included in the subject’s source documentation. 
If the Early Termination Visit is a telephone call, collect as much information as possible. 
Early Termination Visits include subjects who were enrolled but not treated.  
At the clinic visit, the following procedures will be performed;   
• 
Review of subject’s medical records, source document and Diary Card,   
• 
Review of systems, interview of subject to collect unsolicited adverse events, medically 
attended adverse events, AEs leading to withdrawal, SAEs, AESIs, and new onset of 
chronic disease,   

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• 
Interview of subject to collect concomitant medications/vaccinations,   
• 
Symptom-directed physical assessment including measurement of vital signs and a 
check of general appearance,   
• 
Blood sampling for safety laboratory assessment (no blood for immunogenicity 
assessment should be obtained unless this is agreed in advance with the Sponsor),   
• 
Urine sample for pregnancy testing.  
All individuals with neutropenia either ongoing or with onset at last study visit will have 
additional blood draws for complete blood count to be repeated on a regular basis until the 
neutropenia resolves (for classification of neutropenia during the trial, refer to section 
7.1.4.1 Adverse Events of Special Interest). Laboratory results obtained after study 
termination will be maintained in subject medical records and not entered in the eCRF.  
The site will review with the subject the plan of when information relating to the subject’s 
participation in the study may be available (e.g., study results, treatment assignments). It 
will also be discussed how information relating to the subject’s participation in the study 
will be shared with the subject’s healthcare provider, if the subject chooses to share this 
information.  
The site will complete the termination CRF page and this will mark the completion of the 
subject’s participation in the study.  
6.  
TREATMENT OF SUBJECTS  
All vaccines associated with this study are to be stored separately from other vaccines and 
medications in a secure location under appropriate storage conditions with temperature 
monitoring. All vaccines associated with this study must be checked for expiration date 
prior to use. Expired vaccines must not be administered to subjects.  
S6.1  Study Vaccine(s)  
The term ‘study vaccine’ refers to those vaccines provided by the Sponsor, which will be 
evaluated as part of the study objectives. The study vaccine specific to this study is GVGH 
S. sonnei 1790GAHB vaccine. The GVGH GAHB-Diluent will be used as diluent for 
bedside mixing as described below.  
The investigational agent is the GVGH S. sonnei vaccine. The vaccine consists of S. sonnei 
1790-GMMA (200 μg/mL, measured by protein content) adsorbed to Alhydrogel®, (0.7 
mg Al3+/mL) in Tris-buffered saline. The vaccine does not contain any preservative and is 
available as a liquid formulation in single dose vials with 0.7 mL of injectable solution 
containing approximately 140 μg of GMMA (as protein content), adsorbed onto 0.49 mg 
Al3+. It should be stored at +2/+8 °C.   
A diluent, named GAHB-Diluent, visually matching the S. sonnei 1790GAHB vaccine, is 
also supplied for use in this clinical study as a diluent for bedside mixing.  It contains the 

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same formulation ingredients as the active S. sonnei 1790GAHB vaccine, except for the 
Drug Substance antigen 1790-GMMA, and is provided in the same primary packaging as 
the S. sonnei 1790GAHB vaccine.  
  
Aluminum hydroxide is well characterized and used as adjuvant in several licensed 
vaccines. In 1790GAHB, aluminum hydroxide is used as an adsorbent to reduce the 
reactogenicity of LPS and does not enhance the immunogenicity of the GMMA vaccine.  
For further information of study vaccines refer to the Investigator Brochure.  
6.2  
Non-Study Vaccines  
There will be no non-study vaccines to be used.  
6.3  
Vaccine Preparation and Administration  
The investigator or designee will be responsible for oversight of the administration of 
vaccine to subjects enrolled in the study according to the procedures stipulated in this study 
protocol. All vaccines will be administered only by personnel who are qualified to perform 
that function under applicable local laws and regulations for the specific study site.  
Detailed vaccine preparation and administration instructions will be provided to 
investigators in the bedside mixing checklist and instructions prior to study start.  
A S. sonnei 1790GAHB vaccine volume of 0.5 mL will be administered intramuscularly 
after bedside mixing to make a 25 μg protein/0.5 mL dose. Bedside mixing, possibly 
necessary additional labeling of clinical study materials at the study site and vaccine 
administration will be performed according to Sponsor instructions and by trained site staff. 
The site staff responsible for these activities will be personnel who are respectively 
qualified according to applicable local laws and regulations. Sponsor will provide specific 
procedures and training for these activities.    
  
PRECAUTIONS TO BE TAKEN IN ADMINISTERING STUDY VACCINE:  
Prior to vaccination, subjects must be determined to be eligible for study vaccination and it 
must be clinically appropriate in the judgment of the investigator to vaccinate. Eligibility 
for vaccination prior to first study vaccine administration is determined by evaluating the 
entry criteria outlined in protocol sections 4.1, Inclusion Criteria and 4.2, Exclusion 
Criteria.  
Study vaccines should not be administered to individuals with known hypersensitivity to 
any component of the vaccines.  
Standard immunization practices are to be observed and care should be taken to administer 
the injection intramuscularly. Before administering vaccine, the vaccination site is to be 

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disinfected with a skin disinfectant (e.g., 70% alcohol). Allow the skin to dry. DO NOT 
inject intravascularly.  
As with all injectable vaccines, trained medical personnel and appropriate medical 
treatment should be readily available in case of anaphylactic reactions following vaccine 
administration. For example, epinephrine 1:1000, diphenhydramine, and/or other 
medications for treating anaphylaxis should be available.  
6.3.1 Replacement of unusable vaccines  
In addition to the vaccine doses provided for the planned number of subjects (including 
extra doses to allow flexibility in enrolment at the different sites), at least 5% additional 
vaccine doses will be supplied to replace those that are unusable.   
6.4  
Vaccine Administration Error or Overdose of Vaccine  
Vaccine administration error is defined as receiving a dose of study vaccine that was not 
prepared according to bedside mixing instructions or administered by a different route from 
the intended route of administration. An overdose of study vaccine (whether accidental or 
intentional) is defined when a dose higher than dose foreseen in this clinical study, i.e. 25 
µg is administered in one dose of Shigella sonnei 1790GAHB study vaccine subjects.  
Any vaccine administration error or overdose of study vaccine detailed in this protocol must 
be reported as an adverse event, and if the vaccine administration error or overdose is 
associated with a serious adverse event, it must be reported as such within 24 hours to the 
Sponsor.  
6.5  
Prior and Concomitant Medications and Vaccines  
All relevant medications taken or received by the subject within 4 weeks prior to the start 
of the study are to be recorded on the Prior and Concomitant Medications eCRF.  
In addition, the following are considered prior medications for this protocol:   
all medication/vaccines described in the inclusion and exclusion criteria of this protocol 
including the use of antipyretics and/or analgesic medications within 24 hours prior to 
vaccination and ending 12 hours after vaccination must be identified and the reason for 
their use (prophylaxis versus treatment) must be described in the source document and 
Concomitant Medications CRF Section 4.3, Criteria for Delay of Vaccination. Use of 
antipyretic, 24 hours before vaccination is a reason to delay vaccination.  
Medications taken for prophylaxis are those intended to prevent the onset of symptoms. 
Medications taken for treatment are intended to reduce or eliminate the presence of 
symptoms that are present.  

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Concomitant 
medications 
include 
all 
medications 
(including 
vaccines) 
taken 
by/administered to the subject at and after enrolment and must be documented on the 
Concomitant Medications CRF.  
When recording concomitant medications/vaccines, they should be checked against the 
study entry and continuation criteria in section 4, Selection of Study Population to ensure 
that the subject should be enrolled/continue in the study.  
6.6  
Vaccine Supply, Labeling, Storage and Tracking  
Detailed vaccine supply, labeling, storage and tracking instructions will be provided to 
investigators prior to study start.  
The Sponsor will ensure the following:  
• 
Supply the study vaccine.  
• 
Appropriate labeling of all study that complies with the country legal requirements.  
The investigator must ensure the following:  
• 
Acknowledge receipt of the study vaccines by a designated staff member at the site, 
including confirmation that the vaccines were received in good condition.  
• 
Proper storage of the study vaccines, including:  
- 
Storage in a secure, locked, temperature-controlled location.  
- 
The study vaccine must be stored at the respective label storage temperature 
conditions in a safe and locked place. Access to the storage space should be limited 
to authorized study personnel. The storage conditions will be assessed during pre-
study activities under the responsibility of the sponsor study contact.  
- 
Proper storage according to the instructions specified on the labels.  
- 
Appropriate record keeping and inventory of the study vaccines, including regular 
documentation of adequate storage temperature.  
- 
The storage temperature should be continuously monitored with calibrated (if not 
validated) temperature monitoring device(s) and recorded.   
- 
Temperature excursions must be reported in degree Celsius.  
- 
Any temperature excursion outside the range of +2.0 to +8.0 °C impacting 
investigational medicinal products (IMPs) must be reported to the Sponsor. The 
impacted IMPs must not be used and must be stored in quarantine at label 
temperature conditions until usage approval has been obtained from the Sponsor.  
• 
Appropriate use of the study vaccines, including:  
- 
Use only in accordance with the approved protocol.  

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- 
Proper handling, including confirmation that the vaccine has not expired prior to 
administration.  
- 
Appropriate documentation of administration of vaccines to study subjects 
including:  
▪ Date, dosage, batch/lot numbers, expiration dates, unique identifying numbers 
assigned to subjects and study vaccines, and time of vaccine administration. 
This information will be maintained in an accountability log that will be 
reviewed by the site monitor.  
▪ Reconciliation of all vaccines received from the Sponsor. Reconciliation is defined 
as maintaining records of which and how many vaccines were received, which 
vaccines were administered to subjects, which vaccines were destroyed at the 
site, and which vaccines were returned to the Sponsor, as applicable.  
• 
Proper adherence to the local institutional policy with respect to destruction of study 
vaccines.  
• 
Complete record keeping of vaccine use, wastage, return or destruction, including 
documentation of:  
- 
Copy of the site’s procedure for destruction of hazardous material.  
- 
Copy of Destruction Certificate.  
Vaccines that have been stored differently from the manufacturer’s indications must not 
be used unless the Sponsor provides authorization for use. In the event that the use cannot 
be authorized, the Sponsor will make every effort to replace the vaccine supply. All 
vaccines used in conjunction with this protocol must be stored separately from normal 
hospital/practice stocks to prevent unintentional use of study vaccines outside of the clinical 
study setting.  
Monitoring of vaccine accountability will be performed by the study monitor during site 
visits and at the completion of the study.  
At the conclusion of the study, and as appropriate during the course of the study, the 
investigator must ensure that all unused study vaccines, packaging and supplementary 
labels are destroyed locally (upon approval from the Sponsor) or returned to the Sponsor.  
7.  
ASSESSMENTS  
7.1  
Safety Assessment  
The measures of safety used in this study are based on previous study data. They include a 
close vigilance for, and stringent reporting of selected local and systemic adverse events 
routinely monitored in vaccine studies as indicators of reactogenicity.  
An adverse event (AE) is defined as any untoward medical occurrence in a subject or 
clinical investigation subject administered a pharmaceutical product at any dose that does 

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not necessarily have to have a causal relationship with this treatment. Therefore, an AE can 
be any unfavorable and unintended sign (including an abnormal laboratory finding, for 
example), symptom, or disease temporally associated with the use of an investigational 
product, whether or not considered related to the investigational product. This definition 
includes intercurrent illnesses or injuries and exacerbation of pre-existing conditions.  
For the purpose of this trial, AEs will be from the time the subject signs informed consent 
until Visit 4. AEs occurring after the informed consent form is signed but prior to receiving 
study vaccine will be documented as an adverse event and recorded within source 
document. However, any AEs occurring prior to receipt of any study vaccine will be 
analyzed separately from “treatment emergent” AEs (AEs occurring after administration of 
the first study vaccine). All adverse events that are serious, clinically significant as judged 
by the investigators, medically attended and AESI will be collected until study termination 
at visit 5.  
Adverse events are collected as either solicited or unsolicited adverse events. Solicited 
events are derived from organized data collection systems, such as Subject Diaries or 
interview.  
7.1.1  Solicited Adverse Events  
The term “reactogenicity” refers to solicited signs and symptoms (“solicited adverse 
events”) occurring in the hours and days following a vaccination, to be collected by the 
subject for 7 consecutive days, using a pre-defined Subject Diary.  
The following solicited adverse events are included in the Subject Diary. Each adverse 
event is to be assessed using the scoring system reported in parentheses below:   
Solicited Local Adverse Events  
These include erythema, induration and pain at injection site. They will be assessed using 
the scoring system reported in a table below.  Table 6 Grading of solicited local adverse 
events  
Solicited local adverse 
events  
Grade 0 
Absent  
Present - Grading of Severity  
 
Grade 1 Mild  
Grade 2 
Moderate  
Grade 3 
Severe  
Injection site Erythema  
(Captured as 
measurements in 
millimeters)  
1-24 mm  
25-50 mm  
51-100 mm  
> 100 mm  
Injection site Induration  
(Captured as 
measurements in 
millimeters)  
1-24 mm  
25-50 mm  
51-100 mm  
> 100 mm  

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Injection site Pain  
No pain  
Present but does not 
interfere 
with 
activity  
Interferes with 
activity  
Prevents daily 
activity  
Solicited Systemic Adverse Events  
These include headache, arthralgia, chills, fatigue, malaise, myalgia, and fever (body 
temperature measured orally). They will be assessed using the scoring system reported in a 
table below.  
Table 7 Grading of solicited systemic adverse events  
Solicited 
adverse events  
systemic  Grade 0 
Absent  
Present - Grading of Severity*  
Grade 1 Mild  
Grade 2 
Moderate  
Grade 3 
Severe  
Headache  
No headache  Present but does not 
interfere 
with 
activity  
Interferes with 
activity  
Prevents daily 
activity  
Arthralgia  
No  
arthralgia  
Present but does not 
interfere 
with 
activity  
Interferes with 
activity  
Prevents daily 
activity  
Chills  
No chills  
Present but does not 
interfere with activity  Interferes with 
activity  
Prevents daily 
activity  
Fatigue  
No fatigue  
No interference with 
activity  
Some  
interference with 
activity  
Significant; prevents 
daily activity  
Malaise  
No malaise  
No interference with 
activity  
Some  
interference with 
activity  
Significant; prevents 
daily activity  
Myalgia   
No myalgia  
Present but does not 
interfere with activity  Interferes with 
activity  
Prevents daily 
activity  
Fever as a  
Body temperature 
(Captured as  
measurements in degrees 
Celsius)  
≤ 37.9 °C  
≥ 38.0 – 38.9°C  
≥ 39.0 – 39.9°C  
≥ 40.0°C  
Oral Temperature: <35.5 °C to ≥38.0 °C  
Other Solicited Adverse Events  
These include use of analgesics/antipyretics. It will be assessed using the scoring system 
reported in a table below.  
Other Solicited adverse 
events  
Grade 0 
Absent  
Present - Grading of Severity  
 
Grade 1 Mild  
Grade 2 
Moderate  
Grade 3 
Severe  

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Use of analgesics/ 
antipyretics  
Categorized as “yes” or “no”   
 
The study staff must review the data entered into the Subject Diary as described in section 
3.4.2, Tools Used for Data Collection and section 5.3.1, Follow-up Clinic Visit(s).  
Note: Any solicited adverse event that meets any of the following criteria must be entered 
into subjects’ source document (see section 9.1, Source Documentation) and also as an 
adverse event on the Adverse Event CRF:  
• 
Solicited local or systemic adverse event that continues beyond day 7 after vaccination.   
• 
Solicited local or systemic adverse event that leads to a visit to a healthcare provider 
(medically attended adverse event, see section 7.1.3, Evaluation of Adverse Events).  
• 
Solicited local or systemic adverse event leading to the subject withdrawing from the 
study or the subject being withdrawn from the study by the investigator (adverse event 
leading to withdrawal, see section 7.1.3, Evaluation of Adverse Events).  
• 
Solicited local or systemic adverse event that otherwise meets the definition of a serious 
adverse event (see section 7.1.4, Serious Adverse Events).  
7.1.2  Unsolicited Adverse Events  
An unsolicited adverse event 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. In case of such events, subjects will be instructed to contact 
the site as soon as possible to report the event(s). The detailed information about the 
reported unsolicited AEs will be collected by the qualified site personnel during the 
interview and will be documented in the subject’s records.  
Unsolicited AEs that are not medically attended nor perceived as a concern by subjects will 
be collected during interview with the subject and by review of available medical records 
at the next visit (see section 5.3, Post-vaccination Visit(s)).  
7.1.3  Evaluation of Adverse Events  
Every effort should be made by the investigator to evaluate safety information reported by 
a subject for an underlying diagnosis and to capture this diagnosis as the event in the AE 
page. In other words, the practice of reporting only symptoms (e.g., “cough” or “ear pain”) 
are better reported according to the underlying cause (e.g., “asthma exacerbation” or “otitis 
media”).  

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The severity of events reported on the Adverse Events CRF will be determined by the 
investigator as:  
Mild:  
transient with no limitation in normal daily activity.  
Moderate:  
some limitation in normal daily activity. Severe: 
 unable to perform normal daily activity.  
The relationship of the study treatment to an AE will be determined by the investigator 
based on the following definitions:  
1. Not Related  
The AE is not related to an investigational vaccine if there is evidence that clearly indicates 
an alternative explanation. If the subject has not received the vaccine, the timing of the 
exposure to the vaccine and the onset of the AE are not reasonably related in time, or other 
facts, evidence or arguments exist that reasonably suggest an alternative explanation, then 
the AE is not related.  
2. 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. 3. Probably Related  
Exposure to the investigational vaccine and AE are reasonably related in time and no 
alternative explanation has been identified.  
The relationship of the study treatment to an unsolicited AE will be determined by the 
investigator.   
Note: solicited AEs will not be evaluated for relationship to study treatment. Grading for 
severity of solicited local and systemic AEs is described in section 7.1.1, Solicited Adverse 
Events.  
Adverse events will also be evaluated by the investigator for the co-existence of any of the 
other following conditions:  
• 
“Medically attended adverse event”: an adverse event that leads to a visit to a healthcare 
provider.  
• 
“New onset of chronic disease” (NOCD): an adverse event that represents a new 
diagnosis of a chronic medical condition that was not present or suspected in a subject 
prior to study enrolment.  
• 
AEs leading to withdrawal: adverse events leading to study or vaccine withdrawal.  

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• 
Potential immune-mediated diseases (pIMDs): a subset of AEs that include 
autoimmune diseases and other inflammatory and/or neurologic disorders of interest 
which may or may not have an autoimmune aetiology. In this study, only the pIMDs 
reported in the table below will be collected. However if other pIMDs are discovered 
during development of the vaccine, the table will be revised and updated accordingly.  
Musculoskeletal 
disorders  
Spondyloarthritis, 
including 
ankylosing 
spondylitis, 
reactive arthritis (Reiter's Syndrome) and undifferentiated 
spondyloarthritis   
Blood disorders  
Autoimmune neutropenia   
If solicited or unsolicited adverse events have been reported and the subject indicated that 
the symptoms required medical attendance or were of concern, the subject must be 
contacted for further information.  
When the subject is contacted for any of these reasons, the contact must be documented in 
the subject’s source documentation.  
All AEs, regardless of severity, will be monitored until resolution or until the investigator 
assesses them as chronic or stable. All subjects experiencing AEs - whether considered 
associated with the use of the study vaccine or not - must be monitored until symptoms 
subside and any abnormal laboratory values have returned to baseline, or until there is a 
satisfactory explanation for the changes observed, or until death, in which case a full 
pathologist’s report should be supplied, if possible. The investigator’s assessment of 
ongoing Adverse Events at the time of each subject’s last visit should be documented in the 
subject’s medical chart.  
7.1.4  Serious Adverse Events  
A serious adverse event (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.  

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• 
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.  
Adverse events which do not fall into these categories are defined as non-serious.  
It should be noted that a severe adverse event need not be serious in nature and that a serious 
adverse event need not, by definition, be severe.  
Serious adverse events will be captured both on the Vaccines Serious Adverse Event 
(VSAE) form as well as on the AE CRF. All SAEs will be evaluated by the investigator for 
relationship of the event to study vaccine. SAEs that are judged to be possibly or probably 
related to the study vaccine should be reported to the Sponsor as related events. The 
relationship of the study treatment to an SAE will be determined by the investigator based 
on the following definitions:  
1. Related  
The SAE is judged by the investigator to be possibly or probably related to the study vaccine 
on the AE CRF page (see section 7.1.3, Evaluation of Adverse Events).  
2. Not Related  
The SAE is not related if exposure to the study vaccine has not occurred, or the occurrence 
of the SAE is not reasonably related in time, or the SAE is considered unlikely to be related 
to use of the study vaccine, i.e., there are no facts (evidence) or arguments to suggest a 
causal relationship.  
The relationship of the study vaccine to an SAE will be determined by the investigator.  
In addition, SAEs will be evaluated by the Sponsor or designee for “expectedness.” An 
unexpected AE is one that is not listed in the current Summary of Product Characteristics 
or the Investigator’s Brochure or an event that is by nature more specific or more severe 
than a listed event.  
In addition, a pre-existing event or condition that results in hospitalization should be 
recorded on the Medical History CRF. If the onset of an event occurred before the subject 
entered the study (e.g., any pre-planned hospitalization for conditions like cosmetic 
treatments or for non-emergency routine visits for a pre-existing condition), the 
hospitalization would not lead to an AE being classified as serious unless, in the view of 
the investigator, hospitalization was prolonged as a result of participation in the clinical 
study or was necessary due to a worsening of the pre-existing condition.  

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7.1.4.1  
Adverse Events of Special Interest  
Adverse events of special interest (AESIs) are predefined adverse events that will be 
specifically highlighted to the investigator and will be summarized separately. Only AESI 
meeting the definition of SAE will be categorized and reported as such in this study.  
Reactive arthritis (ReA) or Neutropenia will be collected and analyzed as an AESI for this 
study.   
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.  
For diagnosis of ReA, imaging and aspiration are not required (unless clinically indicated).  
Neutropenia is defined as decrease of neutrophil count asymptomatically or 
symptomatically with ANC <1.8x109/L, occurring at 7 days after vaccination. Its graded 
from grade 1 to 4 basing on neutrophil counts as follows: Grade 1 ANC 1.5-<1.8 x 109 /L, 
Grade 2 ANC <1.5 x 109 /L, Grade 3 ANC 1.0- 0.5 x 109 /L, and Grade 4 <0.5 x 109 /L.  
This is completely diagnosed by laboratory testing for complete blood count.   
7.1.5  Methods for Recording Adverse Events and Serious Adverse Events  
Findings regarding Adverse Events must be reported on an Adverse Events CRF, as 
specified in section 7.1.1, Solicited Adverse Events, and on the VSAE form, if applicable, 
which is part of the Investigator Site File. All findings in subjects experiencing AEs must 
be reported also in the subject's source document.  
All SAEs which occur during the course of the study, whether considered to be associated 
with the study vaccination or not and even if the information is incomplete, must be reported 
within 24 hours of the site becoming aware of the event to the Sponsor. Specific 
instructions and contact details for collecting and reporting SAEs will be provided to the 
investigator. Specifically, once an investigator becomes aware that a SAE has occurred in 
a study subject, the investigator (or designate) must complete a paper expedited Adverse 
Events report and forward it to the Sponsor WITHIN 24 HOURS. The report will always 
aimed to be completed as thoroughly as possible with all available details of the event and 
then dated and signed by the investigator (or designate). Even if the investigator does not 
have all information regarding a SAE, the report should still be completed and forwarded 
to the Sponsor within 24 hours. Once additional relevant information is received, the report 
should be updated and forwarded the Sponsor WITHIN 24 HOURS. The investigator will 
always provide an assessment of causality at the time of the initial report.  

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All SAEs are also to be documented on the Adverse Events CRF. Any medication or other 
therapeutic measures used to treat the AE will be recorded on the appropriate CRF(s) in 
addition to the outcome of the AE.  
Only AESI meeting the definition of SAE will be categorized and reported as serious in this 
study by the investigator within 24 hours. However all other AESI irrespective of their 
grading will be recorded in the adverse event page of eCRF and the source documents.   
After receipt of the initial report, representatives of the Sponsor or its designee will contact 
the investigator if it is necessary to obtain further information for assessment of the event. 
Of note, after the initial AE/SAE report, the investigator is required to proactively follow 
each subject and provide additional relevant information on the subject’s condition to the 
Sponsor (within 24 hours for SAEs and Potential ImmuneMediated Disease pIMD, and 
within 2 weeks for pregnancies).  
All SAEs must be reported by the investigator to his/her corresponding EC/IRB and/or 
applicable regulatory authorities in accordance with institutional policy/regulatory 
requirements and adequate documentation of this notification must be provided to the 
Sponsor.  
GSK or its designee must also comply with the applicable regulatory requirement(s) related 
to the reporting of suspected unexpected serious adverse vaccine reactions (also known as 
SUSARs) to the regulatory authority(ies) and the IRB/EC. If a SUSAR or other safety 
signal relating to use of one of the study vaccines is reported to GSK or its designee, the 
Sponsor will communicate the information to the investigator and the investigator will be 
responsible for submitting this information to the EC/IRB and other relevant authorities.  
7.1.5.1  
Post-Study Events  
Any SAE that occurs outside of the protocol-specified follow-up period and considered to 
be caused by the study vaccine must be reported to the Sponsor. These SAEs will be 
processed by the Sponsor as during the course of the study, until 3 months after last subject 
last visit. Instructions and contact details for collecting and reporting these suspected SAEs 
will be provided to the investigator.  
7.1.6  Pregnancies  
To ensure subjects’ safety, each pregnancy in a subject after study vaccination must be 
reported to the Sponsor in due time of the site learning of its occurrence. If the subject 
agrees to submit this information, the pregnancy must be followed to determine outcome, 
including spontaneous or voluntary termination, details of the birth, and the presence or 
absence of any birth defects, congenital abnormalities, or maternal and/or newborn 
complications. This follow-up should occur even if intended duration of safety follow-up 
for the study has ended.  

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Pregnancy data must be recorded on a Pregnancy Report CRF (initial report) and Pregnancy 
Follow-Up CRF (outcome report) and reported to the Sponsor. Instructions and contact 
details for submitting the Pregnancy CRFs will be provided to the investigator.  
Any pregnancy outcome meeting the definition of a SAE (see section 7.1.4, Serious 
Adverse Events) must also be reported on the VSAE Report Form. The following should 
always be considered as SAE.  
• 
Spontaneous pregnancy loss, including:  
−  spontaneous abortion, (spontaneous pregnancy loss before/at 22 weeks of 
gestation)  
 
−  ectopic and molar pregnancy  
 
−  Stillbirth (intrauterine death of foetus after 22 weeks of gestation).  
Note: the 22 weeks cut-off in gestational age is based on WHO-ICD 10 noted in the 
EMA Guideline on pregnancy exposure (EMA, 2006). It is recognized that national 
regulations might be different.  
• 
Any early neonatal death (i.e. death of a live born infant occurring within the first 7 
days of life).   
• 
Any congenital anomaly or birth defect (as per [CDC MACDP] guidelines) identified 
in the offspring of a study subject (either during pregnancy, at birth or later) regardless 
of whether the foetus is delivered dead or alive. This includes anomalies identified by 
prenatal ultrasound, amniocentesis or examination of the products of conception after 
elective or spontaneous abortion.  
7.1.7  Safety Laboratory Measurements  
For list of safety laboratory measurement, refer to synopsis Table 2, Hematological Safety 
Table 3.  
Safety laboratory measurement will be performed as described in Section 3.5, Collection of 
Clinical Specimens.   
Significant alterations in hematology will be clinically assessed by the investigator’s 
medical judgment based on interpretation of deviations from institution’s normal values.   
Any abnormality in laboratory measurements classified as clinically significant must be 
reported in the Adverse Event CRF form.  
If a subject is to have blood drawn testing for safety laboratory for repeat safety assessment 
(i.e., in case of markedly abnormal safety laboratory parameter), investigator’s medical 
judgment will be applied concerning values that would trigger reanalysis and frequency of 
repeats. If neutropenia is observed at a visit, a complete blood count will be repeated on a 
weekly basis until resolution.  

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Safety laboratory assessments will be performed at the site laboratory, and results of these 
tests will be recorded in the source documents and in the CRF.   
7.2  
Efficacy Assessment  
This study has no efficacy endpoints.  
7.3  
Immunogenicity Assessment  
The ELISA methodology used in this study has been adopted based on scientific consensus 
and has been deemed appropriate to describe the immune response against Shigella sonnei 
GMMA in this study.  
The measure of immunogenicity used in this study is IgG ELISA against Shigella sonnei 
OAg. The serologic assays on clinical samples will be performed at GSK, Clinical Serology 
Laboratory, Marburg, Germany, or a delegated laboratory. Section 3: Study Design.  
For reference of visits the measurements are taken, refer to section 3.5 and to the Clinical 
Specimen Laboratory Manual.   
  
 

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8.  
STATISTICAL CONSIDERATIONS  
8.1  
Endpoints  
8.1.1  Primary Endpoint(s)  
8.1.1.1  
Primary Safety Endpoint(s)  
This study has no primary safety endpoint.   
8.1.1.2  
Primary Efficacy Endpoint(s)  
This study has no efficacy measurements.  
 8.1.1.3  
Primary Immunogenicity Endpoint(s)  
The primary immunogenicity endpoint which is memory response, against the OAg of S. 
sonnei will be evaluated by measuring IgG Geometric mean concentrations (GMCs) after 
vaccination as determined by ELISA with O-antigen containing LPS as coating antigen.  
8.1.2  Secondary Endpoint(s)  
8.1.2.1  
Secondary Safety Endpoint(s)  
The measures of safety will include:  
a. Numbers of subjects with deviations from normal values of hematological tests after 
vaccination.  
b. Numbers of subjects with solicited local and systemic reactions during 7 days 
following vaccination. Solicited local reactions include injection site erythema, 
injection site induration and injection site pain; solicited systemic reactions include 
headache, arthralgia, chills, fatigue, malaise, myalgia, and fever (as measured 
orally).  
c. Numbers of subjects with reported unsolicited adverse events (of any nature and 
severity) during 84 days following vaccination.  
d. Number of subjects with reported SAEs throughout the study duration.  
8.1.2.2  
Secondary Efficacy Endpoint(s)  
The study has no secondary efficacy endpoint.  
8.1.2.3 Secondary Immunogenicity Endpoint(s)  
a. IgG Geometric mean concentrations (GMCs) at 7, 14, 28 and 84 days after 
vaccination as determined by ELISA and applicable geometric mean ratios between 
post vaccination and baseline samples.  

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b. Number and percentage of subjects with seroresponse for anti- LPS S. sonnei at 7, 
14, 28 and 84 days after vaccination. 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.Number and percentage of subjects with titers post 
vaccination concentration ≥ 121 EU/ml for anti-LPS S. sonnei at 7, 14, 28 
and 84 days after vaccination.  
c. Number and percentage of subjects with titers post vaccination concentration ≥ 121 
EU/ml for anti-LPS S. sonnei at 7, 14, 28 and 84 days after vaccination.  
A post-vaccination concentration ≥ 121 anti-LPS serum IgG units in the GVGH ELISA 
with O-antigen containing LPS as coating antigen corresponds to a titer of 1:800 in the 
ELISA method used by Cohen et al. (1989 J. Clin. Microbiol. 27:162). This antibody level 
is the median antibody concentration of a set of 87 convalescent subjects previously 
infected by S. sonnei. The value of 121 anti-LPS serum IgG units in the GVGH ELISA was 
determined by calibration against the Cohen ELISA (i.e., the GVGH standard serum was 
tested in Cohen’s lab using the Cohen’s methodology).  
The serologic assays on clinical samples will be performed at GSK, Clinical Laboratory 
Science (CLS), Marburg, Germany, or a delegated laboratory.  
 8.1.3 Exploratory Endpoint(s)  
8.1.3.1  
Exploratory Safety Endpoint(s)  
The study has no exploratory safety endpoint(s).  
8.1.3.2  
Exploratory Efficacy Endpoint(s)  
The study has no exploratory efficacy endpoint(s).  
8.1.3.3  
Exploratory Immunogenicity Endpoint(s)  
Other assays, including serum secretory IgA, might be done to further characterize the 
immune response to the study vaccine. The analysis will be described in the statistical 
analysis plan.  

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8.2  
Success Criteria  
The study has no predefined success criteria. 8.2.1 
 Success Criteria for Primary Objective(s) Not 
applicable.  
8.2.1.1  
Success Criteria for Primary Safety Objective(s) 
Not applicable.  
8.2.1.2  
Success Criteria for Primary Efficacy Objective(s) 
Not applicable.  
8.2.1.3  
Success Criteria for Primary Immunogenicity Objective(s) 
Not applicable.  
8.2.2  Success Criteria for Secondary Objective(s) 
Not applicable.  
8.2.2.1  
Success Criteria for Secondary Safety Objective(s) 
Not applicable.  
8.2.2.2  
Success Criteria for Secondary Efficacy Objective(s) 
Not applicable.  
8.2.2.3  
Success Criteria for Secondary Immunogenicity Objective(s) 
Not applicable.  
8.3  
Analysis Sets  
8.3.1  All Enrolled Set  
All screened subjects who provide informed consent and provide demographic and/or 
baseline screening assessments, regardless of the subject’s randomization and treatment 
status in the study and received a Subject ID.  
8.3.2  All Exposed Set  
All subjects in the enrolled set who receive a study vaccination.  

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8.3.3  Safety Set  
Solicited Safety Set (solicited local and systemic adverse events and other solicited 
adverse events)  
All subjects in the Exposed Set with any solicited adverse event data and/or indicators of 
solicited adverse events.  
Unsolicited Safety Set (unsolicited adverse events)  
All subjects in the Exposed Set with unsolicited adverse event data.  
Overall Safety Set  
All subjects who are in the Solicited Safety Set and/or Unsolicited Safety Set.  
8.3.4  Full Analysis Set (FAS) Efficacy/Immunogenicity Set  
Full Analysis Set Efficacy  
Not applicable.  
Full Analysis Set Immunogenicity  
All subjects in the Enrolled Population who:  
▫ Receive a study vaccination AND provide at least one immunogenicity data at relevant 
time points.  
The FAS will be the primary analysis set for the immunogenicity objective.  
In case of vaccination error, subjects in the FAS sets will be analyzed “as randomized” (i.e., 
according to the study group a subject was assigned).  
8.3.5  Per Protocol (PP) Immunogenicity Set  
All subjects in the FAS / Immunogenicity who:  
• 
Correctly receive the vaccine.  
• 
Have no protocol deviations leading to exclusion (see section 8.3.8, Protocol 
Deviations) as defined prior to analysis.  
• 
Are not excluded due to other reasons defined prior to analysis (see section 8.3.8, 
Protocol Deviations).  
PPS are subsets of FAS and should be always defined even if the objectives do not require 
it.  
Examples for subjects excluded due to other reasons than protocol deviations are   

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-  Subjects who withdrew informed consent.  
8.3.6  Other Analysis Sets 
None.  
8.3.7  Subgroups Not 
applicable.  
8.3.8  Protocol Deviations  
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. A protocol deviation may be a reason to remove data from 
an analysis set at the time of analysis. CSR-reportable protocol deviations will be defined 
as exclusionary from the analysis according to protocol objectives and endpoints, which 
will be specified in the statistical analysis plan. In some cases exclusion of data may be due 
to a reason other than a protocol deviation, i.e. early termination.  
8.4  
Statistical Analysis Plan  
8.4.1  Analysis of Demographic and Baseline Characteristics  
Descriptive statistics (mean, standard deviation, median, minimum and maximum) for age 
and BMI at enrolment will be calculated overall and by vaccine group.   
Distributions of subjects by sex and ethnic origin will be summarized overall and by vaccine 
group.  
8.4.2  Analysis of Primary Objective(s)  
8.4.2.1  
Analysis of Primary Safety Objective(s) 
The study has no primary safety objective.  
8.4.2.1.1  Analysis of Extent of Exposure  
The frequencies and percentages of subjects with vaccination will be summarized overall 
and by study group. Data will be tabulated for the All Enrolled Set.  
8.4.2.1.2  Analysis of Solicited Local, Systemic and Other Adverse Events  
All solicited adverse events will be summarized according to defined severity grading 
scales.   
Frequencies and percentages of subjects experiencing each adverse event will be presented 
for each symptom severity. Summary tables showing the occurrence of any local or 
systemic adverse event overall and at each time point will also be presented.  

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Post-vaccination solicited adverse events reported from day 1 to day 7 will be summarized 
for the intervals day 1-3, day 4-7, day 1-7 by maximal severity and by vaccine group, 
excluding the 30 minute and 4 hour measurement, which will be summarized separately. 
The severity of solicited local adverse events, including injectionsite erythema and 
induration will be summarized according to categories based on linear measurement: 25 to 
50 mm, 51 to 100 mm, >100mm.  
Injection site pain/tenderness and systemic adverse events (except fever) occurring up to 7 
days after vaccination will be summarized according to “mild”, “moderate” or “severe”.  
Each solicited local and systemic adverse event will also be further summarized as “none” 
versus “any”.  
Implausible measurements (for further definition see statistical analysis plan) will be left 
out of the analysis.  
Use of antipyretics and analgesics will be summarized by frequency, by type of use 
(prophylactic versus treatment) and percentage of subjects reporting use. The influence of 
antipyretics and analgesics use on the occurrence of specific adverse events (e.g., fever, 
pain) will be assessed.  
Body temperature will be summarized by 0.5 °C and 1.0 °C increments from 36.0 °C up to 
≥40 °C.  
8.4.2.1.3  Analysis of Unsolicited Adverse Events  
This analysis applies to all adverse events occurring during the study, judged either as 
probably related, possibly related, or not related to vaccination by the investigator, recorded 
in AE CRF, with a start date on or after the date of vaccination. AE starting prior to the 
vaccination will only be listed. The original verbatim terms used by investigators to identify 
adverse events in the CRFs will be mapped to preferred terms using the MedDRA 
dictionary. The adverse events will then be grouped by MedDRA preferred terms into 
frequency tables according to system organ class.  
All reported adverse events, as well as adverse events judged by the investigator as at least 
possibly related to study vaccine, will be summarized according to system organ class and 
preferred term within system organ class. These summaries will be presented by 
vaccination group and by interval of study observation. When an adverse event occurs more 
than once for a subject, the maximal severity and strongest relationship to the vaccine group 
will be counted.  
Separate summaries will be produced for the following categories:   
• 
Serious adverse events  
• 
Adverse events that are possibly or probably related to vaccine  

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• 
Adverse events of special interest  
• 
New onset of chronic disease  
• 
Potential immune-mediated diseases (pIMDs) adverse event leading to withdrawal • 
Adverse events leading to a medically attended visit  
• 
Adverse event by data source.  
Data listings of all adverse events will be provided by subject. In addition, adverse events 
in the categories above will be provided as listed data.  
8.4.2.1.4  Analysis of Safety Laboratory Values  
The investigator must assess all safety laboratory results (see section 7.1.7). Clinically 
significant modifications in blood chemistry, hematology, and urinalysis test values will be 
assessed by medical judgment based on interpretation of deviations from the institution’s 
normal values.  
All laboratory safety data will be analyzed descriptively by study group. Safety laboratory 
data will be shown in a 3 x 3 table by visit using categorization of laboratory according to 
institutional normal reference range (below, within, above).  
 8.4.2.2  
Analysis of Primary Efficacy Objective(s) 
The study has no primary efficacy objective.  
8.4.2.2.1  Statistical Hypotheses  
This Phase 1 safety and immunogenicity trial is aimed to descriptively evaluate the safety 
and immunogenicity profiles of the study vaccines. No specific hypotheses are tested in this 
study.  
 8.4.2.2.2 Analysis Sets  
For more details see (section 8.3 Analysis Sets).  
8.4.2.2.3  
Statistical Methods 
Not applicable.  
8.4.2.3  
Analysis of Primary Immunogenicity Objective(s)  
8.4.2.3.1  Statistical Hypotheses  
This Phase 1 safety and immunogenicity trial is aimed to descriptively evaluate the safety 
and immunogenicity profiles of the study vaccines. No specific hypotheses are tested in this 
trial.  

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8.4.2.3.2  Analysis Sets  
The modified FAS will be the primary analysis set for the immunogenicity objective 
(further details are given in section 8.3, Analysis Sets).  
8.4.2.3.3  Statistical Methods  
Analysis of continuous variables  
The ELISA concentrations will be logarithmically transformed (base10) (to fulfil the 
normal distribution assumption). GMC will be calculated, with their associated two-sided 
95% CIs, by exponentiating the corresponding log-transformed means and their 95% CI.  
Additionally, within-subject GMRs will be computed for GMTs/GMCs at 7, 14, 28 and 84 
days after vaccination versus baseline (day 1). The GMRs and 95% CIs will be constructed 
by exponentiating the mean within-subject differences in log-transformed titers and the 
corresponding 95% CIs.  
Analysis of binary variables  
The number and percentages of subjects with seroresponse from baseline and with high  
antibody level after vaccination (i.e. post vaccination antibody level ≥ 121 IgG units in the 
GVGH ELISA), will be summarized. Two-sided 95% Clopper-Pearson CIs for the 
percentages will be computed.  
Titers below the limit of detection will be set to half that limit for the purposes of analysis. 
Missing values of immunogenicity will be excluded from analyses (i.e. complete-case 
analysis) since they are considered missing completely at random, i.e. not informative and 
with no impact on inferences  
8.4.3  Analysis of Secondary Objective(s)  
8.4.3.1  
Analysis of Secondary Safety Objective(s)  
For more details see Section 8.4.2.1.2 Analysis of Solicited Local, Systemic and Other 
Adverse Events and 8.4.2.1.3 Analysis of unsolicited adverse events.  
8.4.3.1.1  Analysis of Extent of Exposure  
For more details see section 8.4.2.1.1 Analysis of Extent of Exposure.  
8.4.3.1.2  Analysis of Solicited Local, Systemic and Other Adverse Events  
For more details see Section 8.4.2.1.2 Analysis of Solicited Local, Systemic and Other 
Adverse Events.  

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8.4.3.1.3  Analysis of Unsolicited Adverse Events  
For more details see 8.4.2.1.3 Analysis of unsolicited adverse events.  
8.4.3.1.4  Statistical Hypotheses  
For more details see section 8.4.2.2.1, Statistical Hypotheses.  
8.4.3.1.5  Analysis Sets  
For more details see section 8.3, Analysis Sets.  
8.4.3.1.6  Statistical Methods  
For more details see section 8.4.2.2.3, Statistical Methods.  
8.4.3.2  
Analysis of Secondary Efficacy Objective(s) 
The study has no efficacy objective.  
8.4.3.2.1  
Statistical 
Hypotheses Not applicable. 
8.4.3.2.2  
Analysis Sets Not 
applicable.  
8.4.3.2.3  
Statistical Methods 
Not applicable.  
8.4.3.3  
Analysis of Secondary Immunogenicity Objective(s)  
8.4.3.3.1  
Statistical Hypotheses 
Not applicable.  
8.4.3.3.2  Analysis Sets  
For more details see section 8.3, Analysis Sets.  
8.4.3.3.3  Statistical Methods  
For more details see section 8.4.2.2.3, Statistical Methods.  
8.4.4  Analysis of Exploratory Objectives  

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8.4.4.1  
Analysis of Exploratory Safety Objective(s) 
Not applicable.  
8.4.4.2  
Analysis of Exploratory Efficacy Objective(s) 
Not applicable.  
8.4.4.3  
Analysis of Exploratory Immunogenicity Objective(s)  
Other assays, including serum secretory IgA, might be done to further characterize the 
immune response to the study vaccine. The analysis will be described in the statistical 
analysis plan.  
8.5  
Sample Size and Power Considerations of Primary and Secondary Objectives  
No formal statistical sample size and power computations are performed since the 
objectives of the study are to descriptively assess the immunogenicity and safety of the 
investigational vaccine.  
8.6  
Interim Analysis  
No interim analysis of data from this study is planned.  
9. 
SOURCE DOCUMENTATION, STUDY MONITORING AND AUDITING  
Monitoring and auditing will be standardized and performed in accordance with GSK’s or 
delegated contract research organization’s (CRO) standard operating procedures and 
applicable regulatory requirements (e.g., FDA, EMA, and ICH guidelines).  
Prior to enrolment of the first study subject, GSK or delegate will train investigators and/or 
their study staff on the study protocol, all applicable study procedures, documentation 
practices and all electronic systems. CRFs supplied by the Sponsor must be completed for 
each enrolled subject (see section 8.3.1, All Enrolled Set for definition of enrolled subject). 
For subjects not enrolled, information will be stored in source documents only. 
Documentation of screened but not enrolled subjects must be maintained at the site and 
made available for review by the site monitor. Data and documents will be checked by the 
Sponsor and/or monitor.  
9.1  
Source Documentation  
Prior to the start of the study, the site staff participating in the study conduct will be 
instructed on what documents will be required for review as source documents. The kinds 
of documents that will serve as source documents will be agreed between Sponsor or 
delegate and investigator and designees and specified in the SDAF prior to subject 
enrolment.  

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In addition, source documentation must include all of the following: subject identification 
(on each page), eligibility and participation, proper informed consent procedures, dates of 
visits, adherence to protocol procedures, adequate reporting and follow-up of adverse 
events, documentation of prior/concomitant medication/vaccines, study vaccine 
receipt/dispensing/return records, study vaccine administration information, any data 
collected by a telephone conversation with the subject and date of completion and reason.  
The subject must also allow access to the subject’s medical records. Each subject must be 
informed of this prior to the start of the study and consent for access to medical records 
may be required in accordance with local regulations.  
All safety data reported by subjects must be written down in source documents prior to 
entry of the data into CRFs. If there are multiple sources of information (e.g., Subject Diary, 
verbal report of the subject, telephone contact details, medical chart) supporting the 
diagnosis of an adverse event, these sources must be identified in the source documents, 
discrepancies between sources clarified, the ultimate diagnosis must be justified and written 
in the source documents, and this diagnosis must be captured in the Adverse Event CRF 
(AE CRF).   
9.2  
Study Monitoring, Auditing and Source Data Verification  
Prior to enrolment of the first study subject, the Sponsor or its designee (e.g., a CRO) will 
develop a Clinical Monitoring Plan to specify how centralized and/or on-site monitoring, 
including clinical specimens reconciliation, will be performed for the study. Study progress 
will be monitored by the Sponsor or its designee as frequently as necessary to ensure:  
• 
That the rights and well-being of human subjects are protected,  
• 
The reported study data are accurate, complete, and verifiable from the source 
documents and  
• 
The conduct of the study is in compliance with the current approved 
protocol/amendment(s), GCP and applicable regulatory requirements.  
Contact details for the Sponsor team or its designee involved in study monitoring will be 
provided to the investigator. Study data recorded on CRFs will be verified by checking the 
CRF entries against source documents in order to ensure data completeness and accuracy 
as required by study protocol except for those parameters which are specifically described 
in section 7, Assessment being entered directly into the EDC system.  
Data verification may also be performed through a centralized review of data (e.g., checking 
for outliers or other anomalies). Additional documents such as the investigator site file, 
pharmacy records, and informed consent documentation must also be available for review 
if requested. Arrangements for monitoring visits will be made in advance in accordance 
with the monitoring plan, except in case of emergency.  

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The investigator and/or site staff must make source documents of subjects enrolled in this 
study available for inspection by GSK Bio or its representative at the time of each 
monitoring visit and Sponsor audits, when applicable. These documents must also be 
available for inspection, verification and copying, as required by regulations, by officials 
of the regulatory health authorities (e.g., FDA, EMA and others) and/or ECs/IRBs. The 
investigator and study site staff must comply with applicable privacy, data protection and 
medical confidentiality laws for use and disclosure of information related to the study and 
enrolled subjects.  
10. 
DATA MANAGEMENT  
10.1 
Data Entry and Management  
In this study, all clinical data (including, but not limited to, AE/SAEs, concomitant 
medications, medical history, and physical assessments), safety data will be entered onto 
case report forms (CRFs) in a timely fashion by the investigator and/or the investigator’s 
dedicated site staff. Data entered onto CRFs are stored on a secure website. The data 
collected on this secure website are assimilated into an electronic data capture (EDC) 
system, which is compliant with Title 21 Part 11 policies of the Code of Federal Regulations 
(FDA 1997). The data system includes password protection and internal quality checks. 
The EDC system will be designed and validated by the Sponsor prior to activation for data 
entry by sites. The investigator or designated delegate must review data entered and 
electronically sign the CRFs to verify their accuracy.  
Access to the EDC system for data entry or review will require training and distinct 
individual access code assignments to those site staff members who will be entering study 
data and those involved in study oversight who may review study data. Data are collected 
within the EDC system, to which the Sponsor and site monitors have exclusively “read 
only” access.  
10.2 
Data Clarification  
As part of the conduct of the trial, the Sponsor may have questions about the data entered 
by the site, referred to as queries. The monitors, the Sponsor and delegated DM are the only 
parties that can generate a query. All corrections and clarifications will be entered into the 
EDC system and will be identified by the person entering the information, the reason for 
the change, as well as the time of the changes made. If changes are made to a previously 
and electronically signed CRF, the investigator must confirm and endorse the changes.  
10.3 
Data Protection  
The Sponsor respect the subjects’ rights to privacy and will ensure the confidentiality of 
their medical information in accordance with all applicable laws and regulations.  

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The Sponsor as Data Controller according to the European Directive on the protection of 
individuals with regard to the processing of personal data and on the free movement of such 
data (95/46/EC) confirms herewith compliance to Directive 95/46/EC in all stages of Data 
Management.  
11. 
RECORD RETENTION  
Following closure of the study, the investigator must maintain all site study records (except 
for those required by local regulations to be maintained elsewhere) in a safe and secure 
location. The records must be easily accessible, when needed (e.g. audit or inspection), and 
must be available for review in conjunction with assessment of the facility, supporting 
systems, and staff. Where permitted by applicable laws/regulations or institutional policy, 
some or all of these records can be maintained in a validated format other than hard copy 
(e.g. microfiche, scanned, electronic); however, caution needs to be exercised before such 
action is taken. The investigator must ensure that all reproductions are legible and are a true 
and accurate copy of the original and meet accessibility and retrieval standards, including 
re-generating a hard copy, if required. Furthermore, the investigator must ensure that an 
acceptable back-up of the reproductions exists and that there is an acceptable quality control 
procedure in place for making these reproductions.  
The Sponsor will inform the investigator/institution of the time period for retaining these 
records to comply with all applicable regulatory requirements. The minimum retention time 
will meet the strictest standard applicable to a particular site, as dictated by ICH GCP, any 
institutional requirements, applicable laws or regulations, or GSK standards/procedures, 
otherwise, the minimum retention period will default to 25 years after completion of the 
study report.  
The investigator/institution must notify the Sponsor of any changes in the archival 
arrangements, including, but not limited to archival at an off-site facility, transfer of 
ownership of the records in the event the investigator leaves the site. The principles for the 
storage of laboratory samples are provided below:  
Collected samples will be stored for a maximum of 20 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed and 
agreed with the Sponsor.  
12. 
USE OF INFORMATION AND PUBLICATION  
GSK assures that key results of this clinical study will be posted in a publicly accessible 
database within the required time-frame from the end of study as defined in section 3.9, 
End of Study.  

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In accordance with standard editorial, ethical practices and current guidelines of Good 
Publication Practice (Graf 2009), GSK will generally support publication of multicenter 
studies only in their entirety and not as individual center data. In this case, a coordinating 
investigator will be designated by mutual agreement prior to the start of the study. The 
coordinating investigator will also sign the clinical study report on behalf of the principal 
investigators (CPMP/EWP/2747/00). Authorship will be determined by mutual agreement 
and in line with International Committee of Medical Journal Editors authorship 
requirements. Any formal publication of the study in which contribution of GSK personnel 
exceeded that of conventional monitoring will be considered as a joint publication by the 
investigator and the appropriate GSK personnel.  
The Sponsor must be notified of any intent to publish data collected from the study and 
prior approval from the Sponsor must be obtained prior to submission for publication.  

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13. 
ETHICAL CONSIDERATIONS  
13.1  Regulatory and Ethical Compliance  
The study will be conducted in compliance with the protocol, GCP and applicable 
regulatory requirement(s).  
This clinical study was designed and shall be implemented and reported in accordance with 
the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local 
regulations including European Directive 2001/20/EC, GSK codes on protection of human 
rights, and with the ethical principles laid down in the Declaration of Helsinki (European 
Council 2001, US Code of Federal Regulations, ICH 1997).  
The Sponsor will have an account for the trial in the French national database (VRB – 
Volontaires pour la Recherche Biomédicale) where investigator will register each volunteer 
at the day of enrollment.  
After the end of the study, each subject will receive a monetary compensation for a total of 
530 euros to cover for the time spent and any inconvenience due to the study participation. 
This indemnification will be proportional to the number of visits completed as follows:  
- 
50 euros: screening visit  
- 
120 euros: vaccination visit   
- 
90 euros: follow up visit  
13.2 
Informed Consent Procedures  
Eligible subjects may only be included in the study after providing written informed 
consent, as described in section 5.1.1, Informed Consent/Assent. Before the start of the 
study, the investigator will have the informed consent and any other materials that will be 
provided to the subjects reviewed and approved by the IRB/EC. This review and approval 
will be documented and stored with other study documents. The investigator or designee 
must fully inform the subject of all pertinent aspects of the study. A copy of the written 
informed consent will be given to the subject. The subject must be allowed ample time to 
ask about the details of the study and to make a decision as to whether or not to participate 
in the study. The subject must sign the consent form indicating their agreement to 
participate in the study before any study-related procedures are conducted. The informed 
consent process may be conducted up to 21 days prior to vaccination on day 1. If the subject 
is unable to read and write, a witness must be present during the informed consent 
discussion and at the time of informed consent signature.  
Prior to the start of the study, the Sponsor will provide to investigators a proposed informed 
consent form that complies with the ICH GCP guideline and regulatory requirements and 
is considered appropriate for this study. Any changes to the proposed consent form 

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suggested by the investigator must be agreed to by the Sponsor before submission to the 
IRB/EC and a copy of the approved version must be provided to the Sponsor monitor after 
IRB/EC approval.  
Women of childbearing potential should be informed that taking the study medication may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree 
that in order to participate in the study they must adhere to the contraception requirements 
indicated in the protocol for the duration of the study. If case of doubts on the ability of a 
subject to adhere to these requirements, that subject should not be allowed in the study  
13.3 
Responsibilities of the Investigator and IRB/EC  
The protocol and the proposed informed consent form must be reviewed and approved by 
a properly constituted IRB/EC before study start. Properly constituted IRB/EC is defined 
in ICH Guideline for Good Clinical Practice E6 (R1), Section 3 (ICH 1997). A signed and 
dated statement that the protocol and informed consent have been approved by the IRB/EC 
must be given to GSK before study initiation. Prior to study start and at any time the 
protocol is amended during study conduct, the investigator is required to sign a protocol 
signature page confirming his/her agreement to conduct the study in accordance with these 
documents and all of the instructions and procedures found in this protocol and to give 
access to all relevant data and records to GSK monitors, auditors, GSK Clinical Quality 
Assurance representatives, designated agents of GSK, IRBs/ECs, and regulatory authorities 
as required. If an inspection of the clinical site is requested by a regulatory authority, the 
investigator must inform GSK immediately that this request has been made. The 
investigator also responsible for the following:  
• 
Maintaining a list of appropriately qualified persons to whom the investigator has 
delegated significant study-related duties  
• 
Demonstrating the capability of recruiting the required number of suitable subjects 
within the recruitment period  
• 
Demonstrating sufficient time and staffing to properly conduct and complete the study 
within the agreed study period  
• 
Ensuring that all persons assisting with the study are adequately informed about the 
protocol, the investigational product(s), and their study-related duties and functions  
• 
Ensuring that appropriately trained health care professionals are responsible for all 
study-related medical decisions and for ensuring appropriate medical care of subjects 
experiencing any adverse event related to the study  
• 
If permission to do so is given by the subject, ensuring that the subject’s primary 
healthcare provider is informed of the subject’s participation in the study.  
The investigator should not implement any deviation from, or changes of the protocol 
without agreement by the Sponsor and prior review and documented approval/favourable 

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opinion from the IRB/IEC of an amendment, except where necessary to eliminate an 
immediate hazard(s) to study subjects, or when the change(s) involves only logistical or 
administrative aspects of the study (e.g., change in monitor(s), change of telephone 
number(s)). In addition, the investigator, or person designated by the investigator, should 
document and explain any deviation from the approved protocol.  
The investigator may implement a deviation from, or a change of, the protocol to eliminate 
an immediate hazard(s) to study subjects without prior IRB/IEC approval/favourable 
opinion. As soon as possible, the implemented deviation or change, the reasons for it, and, 
if appropriate, the proposed protocol amendment(s) should be submitted:  
(a) To the IRB/IEC for review and approval/favourable opinion,  
(b) To GVGH for agreement and, if required, (c) To the regulatory 
authority(ies).  
13.4  Protocol Amendments  
An amendment is a written description of change(s) to or formal clarification of a study 
protocol which may impact on the conduct of the clinical study, potential benefit of the 
clinical study, or may affect subject safety, including changes of study objectives, study 
design, subject population, sample sizes, study procedures, or significant administrative 
aspects. An administrative change of a study protocol is a minor correction or clarification 
that has no significant impact on the way the clinical study is to be conducted and no effect 
on subject safety (e.g., change of telephone number(s), logistical changes). Protocol 
amendments must be approved by the Sponsor, health authorities where required, and the 
IRB/EC. In cases when the amendment is required in order to protect the subject safety, the 
amendment can be implemented prior to IRB/EC approval. Notwithstanding, the need for 
formal approval of a protocol amendment, the investigator is expected to take any 
immediate action required for the safety of any subject included in this study, even if this 
action represents a deviation from the protocol. In such cases, the Sponsor should be 
notified of this action, the IRB/EC at the study site, and, if required by local regulations, 
the relevant health authority) should be informed within 10 working days.  
  
14.  
REFERENCE LIST  
Berlanda Scorza, F., Colucci, A. M., Maggiore, L., Sanzone, S., Rossi, O., Ferlenghi, I., 
Pesce, I., Caboni, M., Norais, N., Di Cioccio, V., Saul, A. & Gerke, C. 2012. High Yield 
Production Process For Shigella Outer Membrane Particles. Plos One, 7, E35616.  
Code of Federal Regulations (1997): Food and Drug Administration, U.S. Department of 
Health and Human Services: Title 21, Part 11: Electronic Records Electronic Signatures. 
Federal Register 62: 13464  

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12 OCT 16 Version 1                                                                                                        Page 84 of 83  
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managed in Atlas) / Version Date: June 8, 2016  
Cohen, D., Block, C., Green, M. S., Lowell, G. & Ofek, I. 1989. Immunoglobulin M, A, 
And G Antibody Response To Lipopolysaccharide O Antigen In Symptomatic And 
Asymptomatic Shigella Infections. J Clin Microbiol, 27, 162-7.  
Committee for proprietary medicinal products (CPMP), European Agency for the 
Evaluation of Medicinal Products. (1998) Points to consider on clinical investigation of 
medicinal products used in the treatment of osteoarthritis. London, UK.  
Committee for proprietary medicinal products (CPMP), European Agency for the 
Evaluation of Medicinal Products. (2001) Note for guidance on coordinating investigator 
signature of clinical study reports. London, UK.US Department of Health and Human 
Services, Public Health Service, Food and Drug Administration (1992) Guideline for the 
clinical evaluation of analgesic vaccines. Docket No 91D-0425. Rockville, Md.  
European Parliament (1995): Directive 95/46/EC of the European Parliament and of the 
Council of 4 April 2001. Official Journal of the European Communities. L 281/31-39  
European Parliament (2001): Directive 2001/20/EC of the European Parliament and of the 
Council of 4 April 2001. Official Journal of the European Communities. L 121/34-44  
Graf C, Battisti WP, Bridges D (2009). Good publication practice for communicating 
company Sponsored medical research: the GPP2 guidelines. BMJ; 339: b4330  
Kotloff, K. L., Winickoff, J. P., Ivanoff, B., Clemens, J. D., Swerdlow, D. L., Sansonetti, P. J., 
Adak, G. K. & Levine, M. M. (1999). Global Burden Of Shigella Infections: Implications For 
Vaccine Development And Implementation Of Control Strategies. Bull World Health Organ, 
77, 651-66.  
ICH (1997) ICH Harmonised Tripartite ICH Guideline for Good Clinical Practices E6 (R1). 
Federal Register, 62 (90): 25691-25709  
ICH (1998) ICH Harmonised Tripartite ICH Guideline for Statistical Principles for Clinical 
Trials E9. Federal Register, 63 (179): 49583  
Livio, S., Strockbine, N. A., Panchalingam, S. (2014). Shigella Isolates From The Global 
Enteric Multicenter Study Inform Vaccine Development. Clin Infect Dis, 59, 933-41.  
U.S. Department of Health and Human Services, Food and Drug Administration, CBER 
(2009): Guidance for Industry Patient-Reported Outcome Measures: Use in Medical 
Product Development to Support Labeling Claims  
US Department of Health and Human Services, Food and Drug Administration (2007) 
Guidance for Industry: toxicity grading scale for healthy adult and adolescent volunteers 
enrolled in preventive vaccine clinical. Rockville, US.  

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59th World Medical Association General Assembly (October 2008) Declaration of Helsinki 
- Ethical Principles for Medical Research Involving Human Subjects. Seoul, Korea  
  
  
  
  
  
  
 

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Appendix 1: Investigator Agreement  
I agree:  
• 
To conduct the study in compliance with this protocol, any future protocol amendments 
or protocol administrative changes, with the terms of the clinical trial agreement and 
with any other study conduct procedures and/or study conduct documents provided by 
GSK.  
• 
To assume responsibility for the proper conduct of the study at this site.  
• 
That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements.   
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study vaccine(s)/product(s) and other study-related duties and functions as 
described in the protocol.  
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality Assurance 
procedure manual.  
• 
To ensure that no clinical samples (including serum samples) are retained onsite or 
elsewhere without the approval of GSK and the express written informed consent of 
the subject and/or the subject’s legally acceptable representative.   
• 
To perform no other biological assays on the clinical samples except those described 
in the protocol or its amendment(s).   
• 
To co-operate with a representative of GSK in the monitoring process of the study and 
in resolution of queries about the data.  
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational vaccine(s)/product(s), and more generally about 
his/her financial ties with the sponsor. GSK Biologicals will use and disclose the 
information solely for the purpose of complying with regulatory requirements.  
Hence I:  
• 
Agree to supply GSK with any necessary information regarding ownership interest and 
financial ties (including those of my spouse and dependent children).  
• 
Agree to promptly update this information if any relevant changes occur during the 
course of the study and for one year following completion of the study.   
• 
Agree that GSK Biologicals may disclose any information it has about such ownership 
interests and financial ties to regulatory authorities.  

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• 
Agree to provide GSK with an updated Curriculum Vitae and other documents required 
by regulatory agencies for this study.  
eTrack  
study  number  and  
Abbreviated Title  
205905 (S SONNEI MONO GMMA SBVGH-005  
EXT: 001 SUPP (H03_01E1TP)   
EudraCT number  
EudraCT No. 2016-004178-16  
Date of protocol  
Version 1: 12 October 2016  
 
Detailed 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.  
Investigator name  
 
  
  
Signature  
  
Date 
 
  
  
 

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CLINICAL STUDY PROTOCOL H03_01E1TP   
Amendment 1 of 06 February 2017  
  
  
Version  
  
2  
  
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  
  
Shigella sonnei GMMA vaccine in healthy French adult extension Phase I vaccine trial  
  
  
  
  
  
  
  
  
Property of GlaxoSmithKline Biologicals SA (hereafter referred to as GSK Bio)  
  
Confidential  
May not be used, divulged, published or otherwise disclosed without written consent 
of GlaxoSmithKline Biologicals SA  
TABLE OF CONTENTS  

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TABLE OF CONTENTS ..................................................................................................... 
2  
PROTOCOL SYNOPSIS [H03_01E1TP, VERSION 1]..................................................... 7  
Table 2 Time and Event Table- Treatment Period ........................................................ 17  
Table 3 Safety Tests Table ............................................................................................ 20  
LIST OF ABBREVIATIONS ............................................................................................ 
21  
1. 
BACKGROUND AND RATIONALE .................................................................... 23  
1.1 
Background 
.......................................................................................................... 
23  
1.2 
Rationale 
.............................................................................................................. 
24  
2. 
OBJECTIVES 
........................................................................................................... 
25  
2.1 
Primary Objective(s) ............................................................................................ 
25  
2.2 
Secondary Objective(s) ........................................................................................ 
25  
2.3 
Exploratory Objective(s) ..................................................................................... 26  
3. 
STUDY DESIGN ..................................................................................................... 
27  
3.1 
Overview of Study Design ................................................................................... 
27 
3.2 
Study 
Period 
......................................................................................................... 28  
3.3 
Blinding Procedures ............................................................................................. 
28  
3.4 
Data Collection .................................................................................................... 
28  
3.1.1 Data Collected from Subjects ....................................................................... 28 
3.4.2  
Tools 
Used 
for 
Data 
Collection 
.................................................................... 29  
3.5 
Collection of Clinical Specimens ........................................................................ 30  
3.6 
Stopping/Pausing Guidelines ............................................................................... 
32  
3.7 
Data Monitoring Committee ................................................................................ 
33  
3.8 
Premature Withdrawal from Study ...................................................................... 33  
3.9 
End of Study ........................................................................................................ 35  
4. 
SELECTION OF STUDY POPULATION .............................................................. 
36  
4.1 
Inclusion Criteria ................................................................................................. 
36 
4.2 
Exclusion 
Criteria 
................................................................................................ 36  

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4.3  Criteria for Delay of Vaccination ........................................................................ 38  
5. 
STUDY PROCEDURES .......................................................................................... 
39  
5.1 
Pre-vaccination Clinic Visit(s) ............................................................................ 39  
5.1.1 Informed Consent/Assent ............................................................................. 
39 
5.1.2 Screening 
...................................................................................................... 
40 
5.1.3 Enrolment 
..................................................................................................... 
41 
5.1.4 Randomization 
.............................................................................................. 
41 
5.1.4.1 Randomization ......................................................................................... 
41  
5.2 
Vaccination Clinic Visit(s) .................................................................................. 41  
5.2.1 Post-vaccination Procedures ......................................................................... 
42  
5.2.2 Post-vaccination Reminders ......................................................................... 
43  
5.3 
Post-vaccination Visit(s) ...................................................................................... 
44  
5.3.1 Follow-up Clinic Visit(s) .............................................................................. 
44  
5.3.2 Safety Follow-up Calls ................................................................................. 44  
5.4 
Unscheduled Visits .............................................................................................. 
44  
5.5 
Study Termination Visit ...................................................................................... 45  
5.5.1 Early Termination Visit ................................................................................ 
45  
6. 
TREATMENT OF SUBJECTS ................................................................................ 
47 
6.1 
Study 
Vaccine(s) 
.................................................................................................. 47  

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For further information of study vaccines refer to the Investigator Brochure. ............. 47  
6.2 
Non-Study Vaccines ............................................................................................ 
47  
6.3 
Vaccine Preparation and Administration ............................................................. 
47  
6.3.1 Replacement of unusable vaccines .................................................................. 48  
6.4 
Vaccine Administration Error or Overdose of Vaccine ...................................... 48  
6.5 
Prior and Concomitant Medications and Vaccines .............................................. 49  
6.6 
Vaccine Supply, Labeling, Storage and Tracking ............................................... 49  
7. 
ASSESSMENTS 
...................................................................................................... 
51  
7.1 
Safety Assessment ............................................................................................... 
51  
7.1.1 Solicited Adverse Events .............................................................................. 
51 
7.1.2 
Unsolicited 
Adverse 
Events 
.......................................................................... 54  
7.1.3 Evaluation of Adverse Events ...................................................................... 54  
7.1.4 Serious Adverse Events ................................................................................ 
56 
7.1.1.1 Adverse Events of Special Interest ........................................................ 57 
 
7.1.5  Methods for Recording Adverse Events and Serious Adverse Events ......... 58 
7.1.5.1 Post-Study Events .................................................................................. 59 
7.1.6 Pregnancies 
................................................................................................... 
59 
7.1.7 Safety Laboratory Measurements ................................................................. 
60 
7.2 
Efficacy Assessment ............................................................................................ 
60 
7.3 
Immunogenicity Assessment ............................................................................... 
60  
8. 
STATISTICAL CONSIDERATIONS ..................................................................... 
62  
8.1 
Endpoints 
............................................................................................................. 
62  
8.1.1 Primary 
Endpoint(s)...................................................................................... 
62  
8.1.1.1 Primary Safety Endpoint(s) ................................................................... 62  
8.1.1.2 Primary Efficacy Endpoint(s) ................................................................ 
62  
8.1.1.3 Primary Immunogenicity Endpoint(s) ................................................... 
62  
8.1.2 Secondary 
Endpoint(s).................................................................................. 
62  

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8.1.2.1 Secondary Safety Endpoint(s) ............................................................... 62  
8.1.2.2 Secondary Efficacy Endpoint(s) ............................................................ 
62  
8.1.2.3 Secondary Immunogenicity Endpoint(s) ............................................... 
62  
8.1.3 Exploratory Endpoint(s) ............................................................................... 
63  
8.1.3.1 Exploratory Safety Endpoint(s) ............................................................. 
63 
8.1.3.2 
Exploratory 
Efficacy 
Endpoint(s) 
.......................................................... 63  
8.1.3.3 Exploratory Immunogenicity Endpoint(s) ............................................. 63  
8.2 
Success Criteria ................................................................................................... 64  

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8.2.1  Success Criteria for Primary Objective(s) .................................................... 64  
8.2.1.1 Success Criteria for Primary Safety Objective(s) .................................. 64  
8.2.1.2 Success Criteria for Primary Efficacy Objective(s) .............................. 64  
8.2.1.3 Success Criteria for Primary Immunogenicity Objective(s) .................. 64  
 
8.2.2  Success Criteria for Secondary Objective(s) ................................................ 64  
8.2.2.1 Success Criteria for Secondary Safety Objective(s) .............................. 64  
8.2.2.2 Success Criteria for Secondary Efficacy Objective(s) .......................... 64  
8.2.2.3 Success Criteria for Secondary Immunogenicity Objective(s) .............. 64  
 
8.3  Analysis Sets ........................................................................................................ 64 
 
8.3.1  All Enrolled Set ............................................................................................ 64 
 
8.3.2  All Exposed Set ............................................................................................ 64 
 
8.3.3  Safety Set ...................................................................................................... 65 
 
8.3.4  Full Analysis Set (FAS) Efficacy/Immunogenicity Set................................ 65 
 
8.3.5  Per Protocol (PP) Immunogenicity Set ......................................................... 65 
 
8.3.6  Other Analysis Sets....................................................................................... 66 
 
8.3.7  Subgroups ..................................................................................................... 66  
 
8.3.8  Protocol Deviations ...................................................................................... 66  
 
8.4  Statistical Analysis Plan ...................................................................................... 66  
 
8.4.1  Analysis of Demographic and Baseline Characteristics ............................... 66  
 
8.4.2  Analysis of Primary Objective(s) ................................................................. 66  
8.4.2.1 Analysis of Primary Safety Objective(s) ............................................... 66  
 
8.4.2.1.1  Analysis of Extent of Exposure ...................................................... 66  
 
8.4.2.1.2  Analysis of Solicited Local, Systemic and Other Adverse Events . 66  
 
8.4.2.1.3  Analysis of Unsolicited Adverse Events ........................................ 67  
 
8.4.2.1.4  Analysis of Safety Laboratory Values ............................................ 68  
8.4.2.2 Analysis of Primary Efficacy Objective(s) ............................................ 68  
 
8.4.2.2.1  Statistical Hypotheses ..................................................................... 68  
 
8.4.2.2.2  Analysis Sets .................................................................................. 68  
 
8.4.2.2.3  Statistical Methods ......................................................................... 68  
8.4.2.3 Analysis of Primary Immunogenicity Objective(s) ............................... 68  
 
8.4.2.3.1  Statistical Hypotheses ..................................................................... 68  
 
8.4.2.3.2  Analysis Sets .................................................................................. 69  
 
8.4.2.3.3  Statistical Methods ......................................................................... 69  
 
8.4.3  Analysis of Secondary Objective(s) ............................................................. 69  
8.4.3.1 Analysis of Secondary Safety Objective(s) ........................................... 69  
 
8.4.3.1.1  Analysis of Extent of Exposure ...................................................... 69  
 
8.4.3.1.2  Analysis of Solicited Local, Systemic and Other Adverse Events . 69  
 
8.4.3.1.3  Analysis of Unsolicited Adverse Events ........................................ 70  
 
8.4.3.1.4  Statistical Hypotheses ..................................................................... 70  
 
8.4.3.1.5  Analysis Sets .................................................................................. 70 
 
8.4.3.1.6  Statistical Methods ......................................................................... 70 
8.4.3.2 Analysis of Secondary Efficacy Objective(s) ........................................ 70 

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8.4.3.2.1  Statistical Hypotheses ..................................................................... 70 
 
8.4.3.2.2  Analysis Sets .................................................................................. 70 
 
8.4.3.2.3  Statistical Methods ......................................................................... 70 
8.4.3.3 Analysis of Secondary Immunogenicity Objective(s) ........................... 70 
 
8.4.3.3.1  Statistical Hypotheses ..................................................................... 70  
 
8.4.3.3.2  Analysis Sets .................................................................................. 70  
 
8.4.3.3.3  Statistical Methods ......................................................................... 70  
 
8.4.4  Analysis of Exploratory Objectives .............................................................. 71  
8.4.4.1 Analysis of Exploratory Safety Objective(s) ......................................... 71  
8.4.4.2 Analysis of Exploratory Efficacy Objective(s) ..................................... 71  
8.4.4.3 Analysis of Exploratory Immunogenicity Objective(s) ......................... 71  
 
8.5  Sample Size and Power Considerations of Primary and Secondary Objectives.. 71  
 
8.6  Interim Analysis ................................................................................................... 71  
9.  
SOURCE DOCUMENTATION, STUDY MONITORING AND AUDITING ...... 72  
 
9.1  Source Documentation ......................................................................................... 72  
 
9.2  Study Monitoring, Auditing and Source Data Verification ................................. 72  
10.  DATA MANAGEMENT ......................................................................................... 74  
10.1 Data Entry and Management ............................................................................... 74  
10.2 Data Clarification ................................................................................................. 74  
10.3 Data Protection .................................................................................................... 74  
11.  RECORD RETENTION .......................................................................................... 75  
12.  USE OF INFORMATION AND PUBLICATION .................................................. 76  
13.  ETHICAL CONSIDERATIONS ............................................................................. 77  
13.1 Regulatory and Ethical Compliance .................................................................... 77  
13.2 Informed Consent Procedures .............................................................................. 77  
13.3 Responsibilities of the Investigator and IRB/EC ................................................. 78  
13.4 Protocol Amendments ......................................................................................... 79  
14. REFERENCE LIST .................................................................................................. 
80  
APPENDIX 1: INVESTIGATOR AGREEMENT ............................................................ 
82 
PROTOCOL SYNOPSIS [H03_01E1TP, Version 2]  

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Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  
Title of Study:   
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.  
Study Period: Each subject will be 
followed-up for 84 days (approximately 3 
months) after vaccination   
Clinical Phase: Phase 1  
Background and Rationale: The trial H03_01TP evaluated the safety and 
immunogenicity profile of 5 different doses of GVGH Shigella sonnei 1790GAHB 
vaccine (1 µg to 100 µg) compared to placebo, when administered in 3 injections to 50 
healthy adults. The immunogenicity was evaluated at baseline, 28 days after each 
vaccination and at 168 days after third vaccination, by measuring the anti-LPS S. sonnei 
serum IgG. Overall, an antibody response was observed across all the vaccine groups. 
However, at most of the time points, the response was higher in subjects who received 
higher antigen doses (e.g., 25 µg, 50 µg, and 100 µg) than those who received lower doses 
(e.g., 1 µg and 5µg). More specifically, a vaccine dose of 25 µg was very well tolerated 
and induced median antibody concentrations above 121 EU/mL at all post vaccination 
time points. Since 121 EU/mL is the median antibody titer in a panel of 87 convalescents 
previously exposed to S. sonnei infection and therefore protected against re-infection from 
the same serotype, a vaccine dose of 25 µg has the potential to be protective when 
included in a vaccine against S. sonnei.   
After unblinding the immunogenicity database, it was observed that the trial subjects 
could be classified in 2 groups based on S. sonnei antibody concentration at baseline, with 
approximately 50% having undetectable and the other 50% having detectable antiLPS S. 
sonnei serum IgG antibody concentrations. Therefore, for a better understanding of the 
immunological response induced by the vaccine in naïve and primed subjects and for a 
better planning of new clinical studies, additional analyses were carried out. To mitigate 
the small size of study groups, subjects who received vaccines containing 1 µg and 5 µg 
antigen/dose were combined into a single group and then stratified by the presence or 
absence of detectable antibodies at baseline. Same was done for subjects who received 
vaccines containing 25 µg, 50 µg, and 100 µg antigen/dose. As shown in  
 

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Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  

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Figure 1 below, subjects vaccinated with 25 µg, 50 µg and 100 µg vaccines, with 
detectable antibody concentrations at baseline, showed, at all-time points (1 month after 
the first, second and the third vaccinations and 6 months after the third vaccination), 
median antibody concentrations far higher than 121 EU/mL. Subjects vaccinated with 1 
µg and 5 µg vaccines, with detectable antibody concentrations at baseline, showed median 
antibody concentrations slightly higher than 121 EU/mL only at 1 month after the third 
vaccination.  
Figure 1: Median anti-LPS S. sonnei IgG ELISA concentrations and interquartile range 
in subjects with detectable antibodies at baseline (subjects with data at all visits)  
  
Figure 2 below,  with  subjects vaccinated with 25 µg, 50 µg and 100 µg vaccines, with 
undetectable antibody concentrations at baseline, showed median antibody concentrations 
higher than 121 EU/mL at 1 month after the first, second and the third vaccination, while 
at 6 months after the third vaccination the median antibody concentration was less than 
121 EU/mL. Subjects vaccinated with 1 µg and 5 µg vaccines, with undetectable antibody 
concentrations at baseline, did not reach the 121 EU/mL threshold at any time point.  
Figure 2: Median anti-LPS S. sonnei IgG ELISA concentrations and interquartile range 
in subjects with undetectable antibodies at baseline (subjects with data at all visits)  
 
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  

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The results from H03_01TP suggest that GVGH S. sonnei 1790GAHB vaccine, even if 
administered at high doses, may not be sufficiently immunogenic in completely naïve 
adults (who might be a better predictor of antibody response in young naïve children, the 
ultimate target for this vaccine). Although the schedule of immunization used in the trial 
(i.e., 3 injections 1 month apart) may have not been optimal, it remains important to 
evaluate whether the vaccine was able to induce an immunological memory response.  
Therefore the current H03_01E1TP study is designed to further characterize the 
immunogenicity profile of GVGH S. sonnei 1790GAHB vaccine and obtain useful 
information for further clinical development through the administration of a booster dose 
to individuals with undetectable antibodies at baseline in H03_01TP, approximately two 
to three years (i.e. 24 to 36 months) after the third vaccine dose, compared to 
administration of 1 single vaccine dose to placebo recipients with undetectable antibodies 
at baseline in H03_01TP or to naïve subjects who were not part of H03_01TP study. The 
naïve subjects who were not part of H03_01TP study are added in order to have a more 
balanced number of previously unvaccinated and vaccinated subjects in the extension 
trial. In light of the safety and immunogenicity results of H03_01TP and of the potential 
development of a S. sonnei containing Shigella multivalent vaccine, a dose of 25 µg would 

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be preferable for further development. Therefore, the use of this antigen dose is proposed 
for immunization of all subjects to provide further useful information for a more complete 
characterization of this vaccine strength.  
Study Objectives:   
 

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managed in Atlas) / Version Date: June 8, 2016  
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  

GSK  
Confidential  
Protocol H03_01E1TP  
08 FEB 17 Version 2                                                                                                        Page 14 of 83  
PRO-01 TEMP 06 / Atlas No. 293620 Version No.4.1 (hybrid protocol template, not 
managed in Atlas) / Version Date: June 8, 2016  
Primary Objective(s):   
To evaluate the memory response, as measured by anti-LPS S. sonnei serum IgG, 7 days 
after vaccination with a booster dose of GVGH S. sonnei 1790GAHB vaccine in 
individuals who had undetectable antibody titers at baseline in H03_01TP, approximately 
two to three years after the third vaccine dose, compared to administration of 1 single 
vaccine dose to placebo recipients with undetectable antibody titers at baseline in 
H03_01TP or naïve subjects who were not part of H03_01TP study.    
Secondary Objective(s):   
1) Safety:  
a. To evaluate the safety profile of one dose of GVGH S. sonnei 1790GAHB vaccine 
in subjects who previously received three vaccinations with 1790GAHB and in 
subjects receiving one dose 1790GAHB for the first time (either placebo 
recipients in H03_01TP or naïve subjects who were not part of H03_01TP study).  
b. To evaluate the safety profile of one dose of GVGH S. sonnei 1790GAHB vaccine 
in subjects receiving one dose 1790GAHB for the first time and having detectable 
antibodies at baseline of the extension trial.  
2) Immunogenicity:  
a. To evaluate the immunogenicity profile 7, 14, 28 and 84 days after vaccination 
with one dose of GVGH S. sonnei 1790GAHB vaccine in subjects with 
undetectable antibody titers at baseline who previously received three 
vaccinations of GVGH S. sonnei 1790GAHB vaccine in H03_01TP and in 
placebo recipients with undetectable antibody titers at baseline in H03_01TP or 
naïve subjects who were not part of H03_01TP study.  
b. To evaluate the immunogenicity profile of one dose of GVGH S. sonnei 
1790GAHB vaccine in subjects receiving one dose 1790GAHB for the first time 
and having detectable antibodies at baseline of the extension trial.  
c. To evaluate the persistence of anti-LPS S. sonnei serum IgG antibody titers 
approximately two to three years after the third vaccination with 1790GAHB. 3) 
Exploratory:   
Other immunological assays might be performed to further characterize the immune 
response to the study vaccine including serum secretory IgA.  
Study Design:   
 

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PRO-01 TEMP 06 / Atlas No. 293620 Version No.4.1 (hybrid protocol template, not 
managed in Atlas) / Version Date: June 8, 2016  
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  
This is an open label, non-randomized, single center, Phase 1 clinical trial.  The study 
includes a screening visit (performed at study Days -21to -1), one clinical visit with 
vaccination (performed at study Day 1), 4 clinical visits (performed 7, 14, 28 and 84 days 
after vaccination), and 2 phone calls (performed 2 and 6 days after the vaccination).  
Table 1 H03_01TP Study Design    
 H03_01TP    
H03_01E1TP  
Vaccine 
group  
No.  
subjects*  
New enrolled 
subjects  
No. subjects  
 
Vaccine group  
1790GAHB – 1 µg**  
5  
  
5  
1790GAHB – 25 µg  
1790GAHB – 5 µg  
4  
  
4  
1790GAHB – 25 µg  
1790GAHB – 25 µg  
2  
  
2  
1790GAHB – 25 µg  
1790GAHB – 50 µg  
4  
  
4  
1790GAHB – 25 µg  
1790GAHB – 100 µg  
5  
  
5  
1790GAHB – 25 µg  
Placebo  
4  
  
4  
1790GAHB – 25 µg  
Total H03_01TP  
24  
Naïve subjects   
26  
1790GAHB – 25 µg  
Grand total   
 
  
50  
 
 *only subjects with undetectable antibodies at baseline.  
  
  
** µg of total protein  
  

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managed in Atlas) / Version Date: June 8, 2016  
Number of Subjects planned:   
Up to 50 subjects will be enrolled into this trial.  Up to 24 subjects are eligible from the 
parent H03_01TP trial. With respect to naïve subjects who were not part of H03_01TP 
study, considering that in the original H03_01TP population 50% of subjects did not have 
detectable antibodies at baseline, with 26 subjects, approximately 13 subjects should not 
have detectable antibodies. This number combined with that of placebo recipients in 
H03_01TP should be sufficient to allow a balanced contribution of previously 
unvaccinated and vaccinated subjects in the extension trial. Subjects withdrawn or lost to 
follow up will not be replaced. The sample size is not driven by any statistical hypothesis, 
but by availability of subjects from H03_01TP study and fulfilling inclusion criteria.  
Study Population and Subject Characteristics:   
The study population will consist of adult healthy volunteer subjects meeting all inclusion 
and no exclusion criteria.  
The list of inclusion and exclusion criteria is included in protocol section 4, Selection of  
 
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  
Study Population.   

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managed in Atlas) / Version Date: June 8, 2016  
Study Procedures:   
Before any study procedure is performed, informed consent will be obtained; subjects 
will be enrolled only after their eligibility for participation is confirmed by the 
investigator. Safety procedures:  
All subjects providing informed consent will undergo review of medical history, a general 
physical examination including vital signs measurement (temperature, respiratory rate, 
heart rate, blood systolic and diastolic pressure) at the screening visit (study Days -21 to-
1) and at Visit 1 (Day 1) for evaluation of the general health status by clinical assessment 
and verification of inclusion and exclusion criteria. At clinic Visit 2 and at subsequent 
visits, a brief symptom-directed physical examination (if necessary according to 
symptoms the subject has reported) will be performed. Throughout the study it will be 
checked whether continued participation in the study is in the subject best interest in terms 
of safety. For all women of childbearing potential before vaccination at visit 1, a urine 
pregnancy test will be conducted and will also be repeated at visit 5 (Day 85). Women 
with positive test or refusing to perform the test will be immediately excluded from the 
study. Female subjects must use acceptable (defined as oral, injected or implantable 
contraceptives) birth control measures during study participation.  
Blood Draw Procedure:  
Approximately 15 mL blood draw will be obtained for hematological and serological 
(HIV, hepatitis B and C) for subjects who were part of the parent trial (H03_01TP). For 
naïve subjects however 25 mL of blood draw will be obtained for the same hematological 
and serological test mentioned above and in addition HLA-B27 testing as part of the initial 
screening. One additional blood draw of 6 mL for hematological tests will be obtained at 
7 days (Visit 2) and 84 days (Visit 5) after vaccination (see Table 2). Each subject will 
have 20 mL of blood drawn for immunological studies before and 7, 14, 28 and 84 days 
after vaccination. For the purpose of creating a standard reference serum for the 
serological assay, volunteers will be asked to provide an additional blood sample of 20 
mL at 28 days after vaccination (Visit 4).   

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Clinically significant modifications in hematology will be assessed by medical judgment 
based on interpretation of deviations from institution’s normal values and 
recommendations from CBER FDA GUIDANCE FOR INDUSTRY: Toxicity Grading  
 
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  

GSK  
Confidential  
Protocol H03_01E1TP  
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PRO-01 TEMP 06 / Atlas No. 293620 Version No.4.1 (hybrid protocol template, not 
managed in Atlas) / Version Date: June 8, 2016  
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials.  
Vaccination Procedure:  
All eligible subjects will receive one intramuscular vaccination (into the deltoid area of 
the non-dominant arm) with GVGH S. sonnei 1790GAHB vaccine containing  
25µg/dose. Subjects will be observed at the clinic site for 4 hours after vaccination.   
Procedure for Collection of Solicited AEs:  
Beginning in the evening following study vaccine administration (approximately 6 
hours), and daily during the following 6 days following vaccination, diary cards will be 
used to collect solicited local and systemic adverse events including other reactions (i.e. 
body temperature measurements and use of analgesics/antipyretics). A reminder phone 
call will be performed or an email will be sent by the site staff to the subject 2 and 6 days 
following vaccination to remind subjects that the diary card should be completed (no 
update on the status of the subject’s health will be solicited during these contacts that are 
not intended for safety data collection).   
Seven days following vaccination, a clinical visit (Visit 2) will be performed at the study 
site and all information recorded in the diary card will be reported on e-CRF in order to 
document all safety data occurred during the one week follow-up post vaccination.    
In addition to the solicited adverse events data, any unsolicited AE, solicited local and 
systemic AE that continue at 7 days after study vaccination (Visit 2), will be collected 
and recorded at V2, V3 and V4 by clinical study staff in the subject's source document. 
All Serious Adverse Events (SAEs), all AEs leading to vaccine/study withdrawal, all 
Adverse Events of Special Interest (AESI, see below) and all concomitant medications 
associated with those events, will be collected and recorded in the subject's source 
document and on an Adverse Events CRF(s) from the time of vaccination (visit 1) to study 
termination (visit 5). These data will be captured through interview of the subject and by 
review of available medical records.  

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managed in Atlas) / Version Date: June 8, 2016  
Reactive arthritis and neutropenia will be collected and analyzed as AESIs for this study.  
A summary of the main medical and safety data to be collected into the e-CRF during the 
study is provided in Table 2.   
 

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PRO-01 TEMP 06 / Atlas No. 293620 Version No.4.1 (hybrid protocol template, not 
managed in Atlas) / Version Date: June 8, 2016  
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  
Study Vaccines: GVGH S. sonnei (1790GAHB) vaccine  
The investigational agent is the GVGH S. sonnei 1790GAHB vaccine. The vaccine 
consists of S. sonnei OAg containing 1790-GMMA (approximately 200 µg/mL measured 
by protein content) adsorbed to Alhydrogel, (0.7 mg Al3+/mL) in Trisbuffered saline. The 
vaccine does not contain any preservative and is available in a liquid formulation as a 
single dose vials with 0.7 mL of injectable solution containing approximately 140 µg of 
GMMA (as protein content), adsorbed onto 0.49 mg Al3+.   
The vaccine will be used at a dose of 25 µg and will be obtained by bed-side mixing. 
Following dilution, the volume administered by intramuscular route will be 0.5 mL.   
Therefore, each 0.5 mL dose of GVGH S. sonnei 1790GAHB vaccine will contain  
3+. approximately 
25 μg of GMMA total protein and 0.35 mg of Al 

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Primary Endpoint(s):   
This study has no primary efficacy or safety endpoints.   
Primary Immunogenicity Endpoint(s)   
Memory response, against the OAg of S. sonnei will be evaluated by measuring IgG 
Geometric mean concentrations (GMCs) after vaccination as determined by ELISA with 
O-antigen containing LPS as coating antigen.  
Secondary safety endpoint(s):   
The measures of safety will include:  
a. Numbers of subjects with deviations from normal values of hematological tests 
after vaccination.  
b. Numbers of subjects with solicited local and systemic reactions during 7 days 
following vaccination. Solicited local reactions include injection site erythema, 
injection site induration and injection site pain; solicited systemic reactions include 
headache, arthralgia, chills, fatigue, malaise, myalgia, and fever (as measured 
orally).  
c. Numbers of subjects with reported unsolicited adverse events (of any nature and 
severity) during 84 days following vaccination.  
d. Number of subjects with reported SAEs throughout the study duration.  
 
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  

GSK  
Confidential  
Protocol H03_01E1TP  
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PRO-01 TEMP 06 / Atlas No. 293620 Version No.4.1 (hybrid protocol template, not 
managed in Atlas) / Version Date: June 8, 2016  
Secondary Immunogenicity Endpoint(s)  
a. IgG Geometric mean concentrations (GMCs) at 7, 14, 28 and 84 days after 
vaccination as determined by ELISA and applicable geometric mean ratios between 
post vaccination and baseline samples.  
b. Number and percentage of subjects with seroresponse for anti- LPS S. sonnei at 7, 
14, 28 and 84 days after vaccination. 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].  
c. Number and percentage of subjects with titers post vaccination concentration ≥ 121 
EU/ml for anti-LPS S. sonnei at 7, 14, 28 and 84 days after vaccination.  
A post-vaccination concentration ≥ 121 anti-LPS serum IgG units in the GVGH ELISA 
with O-antigen containing LPS as coating antigen corresponds to a titer of 1:800 in the 
ELISA method used by Cohen et al. (1989 J. Clin. Microbiol. 27:162). This antibody level 
is the median antibody concentration of a set of 87 convalescent subjects previously 
infected by S. sonnei. The value of 121 anti-LPS serum IgG units in the GVGH ELISA 
was determined by calibration against the Cohen ELISA (i.e., the GVGH standard serum 
was tested in Cohen’s lab using the Cohen’s methodology).  
The serologic assays on clinical samples will be performed at GSK, Clinical Laboratory 
Science (CLS), Marburg, Germany, or a delegated laboratory.  

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Exploratory Immunogenicity Endpoint(s):   
Other assays, including serum secretory IgA, might be done to further characterize the 
immune response to the study vaccine. The analysis will be described in the statistical 
analysis plan.   
Statistical Analyses:   
Name of Sponsor:  
GlaxoSmithKline  
Biologicals SA   
(GSK Bio )  
Protocol number:  
H03_01E1TP  
Generic name of study vaccine(s):  
GVGH  
Shigella  
sonnei 
 
1790GAHB vaccine  

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Confidential  
Protocol H03_01E1TP  
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PRO-01 TEMP 06 / Atlas No. 293620 Version No.4.1 (hybrid protocol template, not 
managed in Atlas) / Version Date: June 8, 2016  
This Phase 1 safety and immunogenicity extension trial is aimed to descriptively evaluate 
the safety and immunogenicity profiles of the study vaccine, used either a booster (4th 
dose) or as a first dose. No specific hypotheses are tested in this trial. Descriptive analyses 
will be performed to describe and summarize the data (e.g. mean, median, min and max).  
Interim Analysis: No interim analysis is planned for this trial.  
Data Monitoring Committee:   
No ad hoc DSMB will be established for this trial as no interim assessment of safety data 
is anticipated.  
  

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Table 2 Time and Event Table- Treatment Period  
  
Visit Type  
Clinic Visit  
Clinic Visit  
Phone Call  
Clinic Visit  
Clinic Visit  
Clinic Visit  
Clinic Visit  
  
  
  
Study Day  
Visit  
Window  
(Days)  
Visit Number  
  
1  
3, 7  
V1+2 days;  
V1+6 days  
8  
V1+7 days  
15  
V1+14 days  
29  
V1+28 days  
85  
V1+84 days  
-21 to -1  
n/a  
n/a  
0 to +1  
0 to +4  
-3 to +4  
-3 to +7  
Screening  
1  
  
2  
3  
4  
5  
Study Event  
References  
  
  
  
  
  
  
  
Study Treatment  
  
  
  
  
  
  
  
  
Vaccination   
Section 5.2  
  
X  
  
  
  
  
  
Screening and Safety  
  
  
  
  
  
  
  
  
Informed Consent a  
Section 5.1.1  
X  
  
  
  
  
  
  
Medical History  
Sections 5.1.2  
X  
  
  
  
  
  
  
Physical Exam b  
Sections  
5.1.2  
and 5.1.3  
X  
X  
  
  
  
  
  
Symptom-directed 
Exam b   
physical  Section 5.3.1  
  
  
  
X  
X  
X  
X  

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Vital 
signs 
(temperature, 
respiratory rate, heart rate, blood 
systolic and diastolic pressure)  
Sections  
5.1.2  
Screening and 5.2.1  
Post-vaccination  
Procedures  
X  
X  
  
  
  
  
  
Safety blood draw (Hematology) 
c   
Sections 3.5  
and  
7.1.7  
X  
  
  
X  
  
  
X  
 
  
Visit Type  
Clinic Visit  
Clinic Visit  
Phone Call  
Clinic Visit  
Clinic Visit  
Clinic Visit  
Clinic Visit  
  
  
  
Study Day  
Visit  
Window  
(Days)  
Visit Number  
  
1  
3, 7  
V1+2 days;  
V1+6 days  
8  
V1+7 days  
15  
V1+14 days  
29  
V1+28 days  
85  
V1+84 days  
-21 to -1  
n/a  
n/a  
0 to +1  
0 to +4  
-3 to +4  
-3 to +7  
Screening  
1  
  
2  
3  
4  
5  
Study Event  
References  
  
  
  
  
  
  
  
Serology (HIV, hepatitis B and C, 
and HLA-B27 testing only  
for naïve subjects) d   
 Section  3.5  and  
5.1.2  
X  
  
  
  
  
  
  
Pregnancy Test  
 Sections  
3.5  
and 5.1.2  
  
X   
  
  
  
  
X  
Exclusion/Inclusion Criteria  
Section 4  
X  
  
  
  
  
  
  
Post Injection Assessment e  
Section 5.2.1  
  
X  
  
  
  
  
  
Subject Diary Dispensed with 
Training  
Section 5.2.1  
  
X  
  
  
  
  
  

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Subject Diary Reminder Call  
Section 5.2.2  
  
  
X  
  
  
  
  
Subject Diary Reviewed and 
Collected  
Section 5.3.1  
  
  
  
X  
  
  
  
Assess all AEs  
Section 7.1  
X  
X  
  
X  
X  
X  
  
Assess SAEs  
Section 7.1.4  
X  
X  
  
X  
X  
X  
X  
Assess for NOCDs, medically 
attended AEs, AEs leading to 
withdrawal, and AESIs  
Sections 
 
7.1.4.1  and 
7.1.3  
  
X  
  
X  
X  
X  
X   
 
 
  
Visit Type  Clinic Visit  
Clinic Visit  
Phone Call  
Clinic Visit  
Clinic Visit  
Clinic Visit  
Clinic Visit  
 
  
Study Day  
 
  
Visit (Days) 
 
Window  
 
  Visit 
Number  
  
1  
3, 7  
V1+2 days;  
V1+6 days  
8  
V1+7 days  
15  
V1+14 days  
29  
V1+28 days  
85  
V1+84 days  
-21 to -1  
n/a  
n/a  
0 to +1  
0 to +4  
-3 to +4  
-3 to +7  
Screening  
1  
  
2  
3  
4  
5  
Study Event  
References  
  
  
  
  
  
  
  
Assess relevant medications  
 Sections  
5.1.2  
and 6.5  
X  
X  
  
X  
X  
X  
X  
Immunogenicity  
  
  
  
  
  
  
  
  
Serology blood draw   
Section 3.5  
  
X  
  
X  
X  
X  
X  

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 Additional  blood  draw  for  
preparation of standard serum  
Section 3.5  
  
  
  
  
  
X  
  
Study Completion Procedures  
Study Termination f  
Section 5.5  
  
  
  
  
  
  
X  
  
Notes:  
a Informed Consent to be confirmed (oral confirmation) on Visit 1 prior to vaccination  
b Physical examination must be performed by a qualified health professional in accordance with local regulations and licensing requirements designated within the 
Site Responsibility Delegation Log.   
c In case of neutropenia, Complete Blood Count to be repeated on a weekly basis until resolution. If neutropenia occurs at the last study visit, Complete Blood Count 
to be repeated on a regular basis until resolution.  
d The serology tests that are performed at screening are HIV, hepatitis B and hepatitis C and they are conducted for subjects in the parent trial and for the naïve 
subjects. HLA-B27 testing is performed at screening only for the naïve subjects.   
e A post-injection local and systemic adverse event and body temperature and vital signs measurement will be performed approximately 30 minutes and 4 hours 
after vaccination. f Subjects who terminate the study early are recommended to complete certain study-related procedures. See protocol section 5.5 for further 
details.  
Table 3 Safety Tests Table  
HEMATOLOGY  
White Blood Cells (WBC)  
Red Blood Cells (RBC)  
Haemoglobin  
Haematocrit  
Platelets  
Eosinophils  
Basophils  

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Neutrophils  
Monocytes  
Lymphocytes  
Prothrombin time*  
  
SEROLOGY  
HIV antibodies*  
HbsAg*   
Hepatitis C antibodies*   
HLA-B27 testing**  
  
PREGNANCY TEST  
Human chorionic gonadotropin (hCG) in urine  
* Performed at screening only ** Performed at screening only for naïve subjects.  

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LIST OF ABBREVIATIONS  
AE  
 
Adverse Event  
AESI  
 
Adverse Events of Special Interest  
AP  
 
(Statistical) Analysis Plan  
ANC  
 
Absolute Neutrophil Count  
BMI  
 
Body mass index  
CBC  
 
Complete Blood Count  
CI  
 
Confidence Interval  
CLS  
 
Clinical Laboratory Science  
CRF  
 
Case Report Form  
CRO  
 
Contract Research Organization  
DM  
 
Data Management  
DSMB  
 
Data Safety Monitoring Board  
EC  
 
Ethics Committee  
eCRF  
 
Electronic Case Report Form  
EDC  
 
Electronic Data Capture  
ELISA  
 
Enzyme-linked Immunosorbent Assay  
EMA  
 
European Medicines Agency  
EoS  
 
End of Study  
EU  
 
ELISA Unit  
FAS  
 
Full Analysis Set  
FDA  
 
Food and Drug Administration  
GCP  
 
Good Clinical Practices  
GMC  
 
Geometric Mean Concentration  
GMMA  
 
Generalized Modules for Membrane Antigens  
GMR  
 
Geometric Mean Ratio  
GMT  
 
Geometric Mean Titer  
GVGH  
 
GSK Vaccines Institute for Global Health  
HIV  
 
Human Immunodeficiency Virus  
IB  
 
Investigator’s Brochure  
ICF  
 
Informed Consent Form  
ICH  
 
International 
Conference 
on 
Harmonisation 
of 
Technical 
Requirements for Registration of Pharmaceuticals for Human Use  
IRB  
 
Institutional Review Board  
ITT  
 
Intention-To-Treat  
MSD  
 
Moderate to Severe Diarrhea  
LPS  
 
Lipopolysaccharide  
LSLV  
 
Last Subject Last Visit  
MedDRA  
 
Medical Dictionary for Regulatory Activities  
NOCD  
 
New onsets of chronic diseases  
OAg  
 
O antigen (of Shigella sonnei)  
pIMD  
 
Potential Immuno-Mediated Diseases   

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PP  
 
Per Protocol  
ReA  
 
Reactive arthritis  
SAE  
 
Serious Adverse Event  
SDA  
 
Source Data Agreement  
SDAF  
 
Source Documentation Agreement Form  
SOC  
 
System Organ Class  
SOP  
 
Standard Operating Procedure  
SPC  
 
Summary of Product Characteristics  
WHO  
 
World Health Organization  
  
  
  
  
  
  
  
 

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1. 
BACKGROUND AND RATIONALE  
1.1  
Background  
Shigellosis remains a major health problem in developing countries with approximately  
100 million cases per year mostly in children ≤5 years (Kotloff et al., 1999). Antibiotic 
resistance of Shigella is increasing and no vaccine is currently available against shigellosis.  
Livio et al showed that a quadrivalent vaccine containing S. sonnei and 3 
serotype/subserotypes of S. flexneri (S. flexneri 2a, S. flexneri 3a, and S. flexneri 6) can 
provide broad coverage against Shigella serotypes (up to 65%) (Livio et al., 2014), which 
cause shigellosis in the developing world, and can also provide broad coverage for travelers.   
In this view, GSK Vaccines Institute for Global Health (GVGH) developed the S. sonnei 
1790GAHB vaccine that has been tested in two Phase 1 trials in European adult population: 
one trial of the trials (protocol H03_01TP), looking at the intramuscular (IM) administration 
was conducted in France. In that study different antigen doses were evaluated and showed 
to be safe and well tolerated. More specifically, the trial evaluated the safety and 
immunogenicity profile of 5 different doses of GVGH Shigella sonnei 1790GAHB vaccine 
(1 µg to 100 µg) compared to placebo, when administered in 3 injections 1 month apart to 
50 healthy adults. The immunogenicity was evaluated at baseline, 28 days after each 
vaccination and at 168 days after third vaccination, by measuring the anti-LPS S. sonnei 
serum IgG. Overall, an antibody response was observed across all the vaccine groups. 
However, at most of the time points, the response was higher in subjects who received 
higher antigen doses (i.e., 25 µg, 50 µg, and 100 µg) than those who received lower doses 
(i.e., 1 µg and 5µg).   
More specifically, a vaccine dose of 25 µg was very well tolerated and induced median 
antibody concentrations above 121 EU/mL at all post vaccination time points. Since 121 
EU/mL is the median antibody titer in a panel of 87 convalescents previously exposed to  
S. sonnei infection and therefore protected against re-infection from the same serotype 
(Cohen et al, 1989), a vaccine dose of 25 µg has the potential to be protective when included 
in a vaccine against S. sonnei. After unblinding the immunogenicity database, it was 
observed that the trial subjects could be grouped in 2 groups based on S. sonnei antibody 
concentration at baseline, with 50% having undetectable and 50% having detectable anti-
LPS S. sonnei serum IgG antibody concentrations. Therefore, for a better understanding of 
the immunological response induced by the vaccine in naïve and primed subjects and for a 
better planning of new clinical studies, additional analyses were carried out. To mitigate 
the small size of study groups, subjects who received vaccines containing 1 µg and 5 µg 
antigen/dose were combined into a single group in which those with detectable antibody 
concentrations at baseline, showed median antibody concentrations slightly higher than 121 
EU/mL only at 1 month after the third vaccination. Same was done for subjects who 
received vaccines containing 25 µg, 50 µg, and 100 µg antigen/dose, among whom those 
with detectable antibody concentrations at baseline, showed, at all-time points (1 month 

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after the first, second and the third vaccinations and 6 months after the third vaccination), 
median antibody concentrations far higher than 121 EU/mL.   
Based on the results from this trial, it has been decided to proceed with further development 
using only the IM route of immunization and a dose of 25 µg was selected as the lowest 
dose that in phase 1 induced antibody titers comparable to antibodies in a population of 
convalescent subjects after natural infection already after the first vaccination.  
The results from H03_01TP suggest that 1790GAHB, even if administered at high doses, 
may not be sufficiently immunogenic in completely naïve adults (who might be a better 
predictor of antibody response in young naïve children, the ultimate target for this vaccine). 
Although the schedule of immunization used in the trial (i.e., 3 injections 1 month apart) 
may have not been optimal, it remains important to evaluate whether the vaccine was able 
to induce an immunological memory response.   
1.2  
Rationale  
The current H03_01E1TP study is designed to further characterize the immunogenicity 
profile of GVGH S. sonnei 1790GAHB vaccine and obtain useful information for further 
clinical development through the administration of a booster dose to individuals with 
undetectable antibodies at baseline in H03_01TP, approximately two to three years (i.e., 24 
to 36 months) after the third vaccine dose, compared to administration of 1 single vaccine 
dose to placebo recipients with undetectable antibodies at baseline in H03_01TP or to naïve 
subjects who were not part of H03_01TP study. The naïve subjects who were not part of 
H03_01TP study are added in order to have a more balanced number of previously 
unvaccinated and vaccinated subjects in the extension trial. In light of the safety and 
immunogenicity results of H03_01TP and of the potential development of a S. sonnei 
containing Shigella multivalent vaccine, a dose of 25 µg would be preferable for further 
development. Therefore, the use of this antigen dose is proposed for immunization of all 
subjects to provide further useful information for a more complete characterization of this 
vaccine strength.  
2. 
OBJECTIVES  
2.1  
Primary Objective(s)  
Primary Safety Objective(s)   
This study has no primary safety objective  
Primary Efficacy Objective(s)   
This study has no primary efficacy objective  
Primary Immunogenicity Objective(s)   

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To evaluate the memory response, as measured by anti-LPS S. sonnei serum IgG, 7 days 
after vaccination with a booster dose of GVGH S. sonnei 1790GAHB vaccine in individuals 
who had undetectable antibody titers at baseline in H03_01TP, approximately two to three 
years after the third vaccine dose, compared to administration of 1 single vaccine dose to 
placebo recipients with undetectable antibody titers at baseline in H03_01TP or naïve 
subjects who were not part of H03_01TP study.  
2.2  
Secondary Objective(s)  
Secondary Safety Objective(s)   
a. To evaluate the safety profile of one dose of GVGH S. sonnei 1790GAHB vaccine in 
subjects who previously received three vaccinations with 1790GAHB and in subjects 
receiving one dose 1790GAHB for the first time (either placebo recipients in 
H03_01TP or naïve subjects who were not part of H03_01TP study).  
b. To evaluate the safety profile of one dose of GVGH S. sonnei 1790GAHB vaccine in 
subjects receiving one dose 1790GAHB for the first time and having detectable 
antibodies at baseline of the extension trial. Secondary Efficacy Objective(s)   
This study has no secondary efficacy objectives.   
Secondary Immunogenicity Objective(s)   
a. To evaluate the immunogenicity profile 7, 14, 28 and 84 days after vaccination with 
one dose of GVGH S. sonnei 1790GAHB in subjects with undetectable antibody 
titers at baseline who previously received three vaccinations of 1790GAHB in 
H03_01TP and in placebo recipients with undetectable antibody titers at baseline in 
H03_01TP or naïve subjects who were not part of H03_01TP study.  
b. To evaluate the immunogenicity profile of one dose of GVGH S. sonnei 1790GAHB 
vaccine in subjects receiving one dose 1790GAHB for the first time and having 
detectable antibodies at baseline of the extension trial.  
c. To evaluate the persistence of anti-LPS S. sonnei serum IgG antibody titers 
approximately two to three years after the third vaccination with 1790GAHB.  
2.3  
Exploratory Objective(s)  
Other immunological assays might be performed to further characterize the immune 
response to the study vaccine including serum secretory IgA.  
 

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3. 
STUDY DESIGN  
3.1  
Overview of Study Design  
This is an open label, non-randomized, single center, Phase 1 clinical trial designed to 
further characterize the immunogenicity profile of GVGH S. sonnei 1790GAHB vaccine 
through the administration of a booster dose to individuals with undetectable antibodies at 
baseline in H03_01TP parent study, approximately two to three years (i.e., 24 to 36 months) 
after the third vaccine dose, compared to administration of 1 single vaccine dose to placebo 
recipients with undetectable antibodies at baseline in H03_01TP parent study  or to naïve 
subjects who were not part of H03_01TP study. The study includes a screening visit 
(performed at study Days -21 to -1), one clinical visit with vaccination (performed at study 
Day 1), 4 clinical visits (performed 7, 14, 28 and 84 days after vaccination), and 2 phone 
calls or email contacts (performed 2 and 6 days after the vaccination). No subject or study 
staff will be blinded for any study procedure.  
During the screening period, subjects giving informed consent will be screened for general 
health status. No pharmacokinetic tests will be performed as evaluation of pharmacokinetic 
properties is not required for vaccines unless new delivery systems are employed or when 
the vaccine contains novel adjuvants or excipients (Berlanda Scorza et al., 2012). Subjects 
who meet all inclusion criteria and none of the exclusion criteria, with screening tests within 
normal values and women of child bearing potential with negative urine pregnancy test at 
V1 will be eligible for enrollment. Female subjects of child bearing potential must use birth 
control measures during study participation.  
Up to 50 subjects will be enrolled into this trial. 24 subjects are eligible from the parent 
H03_01TP trial. With respect to naïve subjects who were not part of H03_01TP study, 
considering that in the original H03_01TP population 50% of subjects did not have 
detectable antibodies at baseline, with 26 subjects, it is anticipated that at least 13 subjects 
should not have detectable antibodies. This number combined with that of placebo 
recipients in H03_01TP should be sufficient to allow a balanced contribution of previously 
unvaccinated and vaccinated subjects in the extension trial. Subjects withdrawn or lost to 
follow up will not be replaced. The sample size is not driven by any statistical hypothesis, 
but by availability of subjects from H03_01TP study and fulfilling inclusion criteria. 
Subjects will be recruited as detailed in table 1.  
No randomization will be required since all subjects will receive the same dose of the same 
vaccine.  
Screening/baseline clinical safety labs will take place before Visit 1 (from -21 up to -1 day). 
All subjects providing informed consent will undergo review of medical history, a complete 
physical examination including vital signs measurement (temperature, respiratory rate, 
heart rate, blood systolic and diastolic pressure) at the screening visit (study Day -21 to -1) 
and at visit 1 (Day 1) for evaluation of the general health status by clinical assessment and 
verification of inclusion and exclusion criteria. At clinic visit 2 and at subsequent visits, a 

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brief symptom-directed physical examination (if necessary according to symptoms the 
subject has reported) will be performed.   
A blood sample will be obtained as part of the initial screening for hematology and serology 
(HIV, hepatitis B and C, and for HLA-B27 testing only for naïve subjects). Blood will be 
collected for hematology also on day 8 and 85 (visit 2 and 5 respectively). Each consented 
subject will have blood collected before vaccination on day 1 for baseline immunological 
testing and on day 8, 15, 29 and 85 (visit 2, 3, 4, and 5 respectively) post vaccination for 
immunological. Additional blood draw for preparation of standard serum will be done on 
day 29 post vaccination (visit 4). Urine pregnancy test will be done at visit 1 prior to 
vaccination and at visit 5. All individuals with neutropenia occurring at any time during the 
study will have additional blood draws to repeat complete blood count on a weekly basis 
until the neutropenia resolves. If neutropenia occurs at the last study visit, Complete Blood 
Count to be repeated on a regular basis until resolution (for classification of neutropenia 
during the trial, refer to Section 5.4 Unscheduled Visits).  
Subjects will be observed at the clinic for 4 hour after vaccination on visit 1. Vital signs 
will be collected before vaccination and at 30 minutes and 4 hours post vaccination. Before 
leaving the clinic,  they will be given a paper dairy card and trained to record in any adverse 
events occurring before visit 2 and will be reminded by phone call or email on day 3 and 7 
post vaccination. These dairy cards will be collected and reviewed on day 8 post vaccination 
(visit 2).  
Any unsolicited AE until visit 4, SAEs until study termination, all AEs leading to study 
withdrawal, reactive arthritis and severe neutropenia (AESI) and all concomitant 
medications associated with those events, will be collected and recorded in the subject’s 
source document and in the eCRF. Further details on study procedure are found in sections 
5, Study Procedures and 7, Assessments.  
3.2  
Study Period  
Each subject should expect to participate in the study for 85 days, from the time of 
enrolment through the last study visit.  
3.3  
Blinding Procedures  
No blinding procedures will be applied for this study.  
3.4  
Data Collection  
3.4.1  Data Collected from Subjects  
The following data will be collected from each subject over the duration of their study 
participation:  
• 
Demographic Information  

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• 
Medical History  
• 
Post-vaccination immediate reactions  
• 
Vital signs including but not limited to body temperature  
• 
Adverse Events  
• 
Concomitant Medications  
All data collected must only be identified using the GSK Subject ID and Subject code, as 
described in section 5.1.4, Randomization.  
3.4.2  Tools Used for Data Collection  
Subject Diary  
Paper Diaries, hereafter referred to as Subject Diaries will be the only source document 
allowed for solicited local and systemic adverse events (including body temperature 
measurements), starting approximately 6 hours post-vaccination and collected by the 
subject. The following additional rules apply to documentation of safety information 
collected in the Subject Diary.  
The Investigator or delegated staff should monitor the Subject’s Diary status throughout the 
study for compliance and any solicited local and systemic adverse events that were of 
concern to the subject.  
1. No corrections or additions to the information recorded by the subject within the Subject 
Diary will be allowed after it is delivered to the site.  
2. Any blank or illegible fields on the Subject Diary must be described as missing in the 
CRF.  
Case Report Forms  
An electronic data capture (EDC) system (e.g., Inform™) will be used to expedite the entry 
of data. A qualified site staff member(s) will enter data in English into the web enable EDC 
system in a timely manner; the data will be stored in GSK clinical database management 
system. eCRF data will be reviewed routinely by GSK Data Management (DM) Group and 
GSK clinical monitors or representatives.  
The information from the diary will be entered in the eCRF at visit 2. All data not recorded 
directly on the eCRFs must be verified by checking eCRF entries against source documents 
in order to ensure that the data have been completely and accurately reported as required 
by the study protocol.  
Source data verification will be performed and recorded following GSK internal SOP. The 
subject must also allow access to his/her medical records. Each subject will be informed of 
this prior to the start of the study.  

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The following additional rules apply to documentation of Subject Diary information 
collected in the CRFs:  
1. The site must enter all readable entries from the Subject Diary into the eCRF, including 
those values that may be biologically implausible (e.g. body temperature: 400°C).  
2. Any illegible or implausible data should be reviewed with the subject. If an underlying 
solicited or unsolicited adverse event is described on review with the subject, this 
should be described in the source document and reported as an unsolicited adverse event 
in the Adverse Event CRF (e.g., if the subject above confirms body temperature of 40°C 
on the day in which body temperature: 400°C was written into his/her Subject Diary, 
this fever of 40°C should be recorded in the Adverse Event CRF).  
3. Any newly described safety information (including a solicited adverse event) must not 
be written into the Subject Diary and must be described in the study file (studyspecific 
workbook) as a verbally reported adverse event. Any adverse event reported in this 
fashion must be described as an unsolicited adverse event and therefore entered on the 
Adverse Event CRF.  
3.5  
Collection of Clinical Specimens  
Collected samples will be used for protocol mandated research and purposes related to the 
improvement, development and quality assurance of the laboratory tests described in this 
protocol. This may include the management of the quality of these tests, the maintenance 
or improvement of these tests, the development of new test methods, as well as making sure 
that new tests are comparable to previous methods and work reliably.  
It is also possible that future findings may make it desirable to use the samples acquired in 
this study for future research, not described in this protocol. Therefore, all subjects in 
countries where this is allowed/all subjects will be asked to give a specific consent to allow 
the Sponsor or a contracted partner to use the samples for future research. Future research 
will be subject to the laws and regulations in France and will only be performed once an 
independent Ethics Committee or Review Board has approved this research. Information 
on further investigations and their rationale can be obtained from GSK.   
Any sample testing will be done in line with the consent of the individual subject If 
additional testing is performed, the marker priority ranking given in the table below may 
be changed.  
Table 4 Blood For Immunological purposes  
Blood sampling timepoint  
Subset 
/Subcohort 
Name   
No. subjects  Component  
Components  
priority  
rank 
  
Type of contact and 
timepoint  
Sampling 
timepoint  
  
Screening (Day -21 to 1) 
Pre-Vacc  
All subjects  
50  
HIV*  
NA  
All subjects  
50  
anti-HBsAg*  
All subjects  
50  
Hepatitis C*   

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Naïve subjects  26  
HLA-B27  
Visit 1 (Day 1)  
Pre-Vacc  
  
50  
Anti LPS IgG 
ELISA  
NA  
Visit 2 (Day 8)  
Post-Vacc 1    
50  
Anti LPS IgG 
ELISA  
NA  
Visit 3 (Day 15)  
Post-Vacc 2    
50  
Anti LPS IgG  NA  
Visit 4 (Day 29)  
Post-Vacc 3    
50  
Anti LPS IgG  1  
Standard 
Serum  
  
50  
Standard pool 
for ELISA  
2  
Visit 5 (Day 85)  
Post-Vacc 4    
50  
Anti LPS IgG  NA  
* The results of this testing might potentially impact the subject medical care   
Processing of each specimen should be completed by a qualified site member and in 
accordance with the study-specific laboratory manual. Testing of clinical specimens will be 
performed by GSK Clinical Laboratory Science (CLS), Marburg, (Germany) or a delegated 
laboratory. Refer to the study-specific laboratory manual for additional details.   
Blood Specimens  
Approximately 15 mL blood draw will be obtained for hematological and serological (HIV, 
hepatitis B and C for subjects who were in the parent study. Naïve subjects will however 
have 25mL of blood drawn for HLA-B27 testing in addition of the hematological and 
serological (HIV, hepatitis B and C) tests as part of the initial screening. One additional 
blood draw of 6 mL for hematological tests will be obtained at 8 days (Visit 2) and 85 days 
(Visit 5) after vaccination (see Table 2). Each subject will have 20 mL of blood drawn for 
immunological studies before vaccination at Day 1 and 8, 15, 29 and 85 days after 
vaccination. For the purpose of creating a standard reference serum for the serological 
assay, study subjects will provide an additional blood sample of 20 ml at 29 days after 
vaccination.  
All individuals with neutropenia occurring at any time during the study will have additional 
6mL blood draws to repeat complete blood count on a weekly basis until the neutropenia 
resolves.  
Clinically significant modifications in hematology will be assessed by medical judgment 
based on interpretation of deviations from institution’s normal values and recommendations 
from CBER FDA GUIDANCE FOR INDUSTRY: Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials.  
The total amount of blood collected over the study period per subject will be approximately 
157 mL including screening for HLA for a subject who was not part of the parent study and 
the additional blood sample at day 29 for the standard pool serum for immunogenicity and 
excluding possible repeats of hematological tests in case of neutropenia.  

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Serum samples will be stored frozen below -20ºC. The sera aliquots will be shipped 
according to guidelines provided by GSK to the laboratories for analysis. The serologic 
assays will be conducted at the GSK Clinical Laboratory Science, Marburg, (Germany) or 
a delegated laboratory.  
Aliquots of sera will be archived for 20 years at the GSK laboratory in Marburg (Germany) 
for future research on immunogenicity of the Shigella vaccines. Study-related future 
research may include additional evaluation of immunogenicity on Shigella sonnei (i.e. IgM, 
IgA against the O antigen or IgG against other antigens of Shigella sonnei). It may not be 
possible to contact individual participants in the future in order to disseminate results 
obtained from research conducted on archived samples. However, these results, if relevant, 
will be published in peer-reviewed journals and disseminated to the scientific community. 
An archival time of 20 years should cover the entire vaccine development time, including 
the possibility to address potential questions from regulators during the registration time.  
Complete instructions for processing, labeling, storage and shipping of samples are 
included in the Clinical Specimen Laboratory Manual provided to the investigators and 
available in the Investigator Site File.  
Blood samples must be collected in the appropriate manner, using exclusively materials and 
guidelines supplied by GSK. The investigator must ensure that his/her personnel and the 
laboratory(ies) under his/her supervision comply with this requirement. The results of 
safety testing will be recorded in the source document and eCRF.  
Urine Specimens  
In this study urine samples will be collected from women of childbearing potential only 
for pregnancy testing before vaccination at Day 1 (visit1) and at study termination (visit 
5).  
3.6  
Stopping/Pausing Guidelines  
There are no predetermined stopping rules in this study. Subjects may be withdrawn from 
the study according to investigator discretion as described in section 3.8, Premature 
Withdrawal from Study.  
3.7  
Data Monitoring Committee  
No Data Monitoring Committee will be established for this study.  
3.8  
Premature Withdrawal from Study  
Subjects may withdraw at any time, or be dropped from the study at the discretion of the 
investigator should any untoward effects occur and/or for safety reasons. In addition, a 
subject may be withdrawn by the investigator or Sponsor if he/she violates the study plan 

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or for administrative reasons. The investigator or study coordinator must notify the Sponsor 
immediately when a subject has been withdrawn due to an adverse event.  
The circumstances above are referred to as premature withdrawal from the study, and the 
reason for premature withdrawal should be clearly documented and detailed in the source 
documentation. The investigator should make every attempt to evaluate the subject’s safety, 
including resolution of ongoing AEs, at the time of premature withdrawal. If a subject wants 
to withdraw from the study prior to the last planned study visit, the subject will be asked to 
be followed for safety for the duration of the study. When a subject withdraws, or is 
withdrawn, from the study, the procedures described in section 5.5.1, Early Termination 
Visit should be completed if possible.  
The reasons for premature withdrawal from the study include: Adverse event, death, 
withdrawal of consent, lost to follow-up, administrative reason, and protocol deviation. 
These reasons are described in greater detail below.  
Adverse Event  
For any subject withdrawn from study participation prior to the planned Study Termination 
Visit, it is important to determine if an AE was associated with the reason for discontinuing 
the study. This AE must be identified on the AE CRF page by indicating “Withdrawn from 
study due to AE”. Any ongoing AEs at the time of study withdrawal must be followed until 
resolution or stabilization.  
Death  
For any subject withdrawn from study participation due to death, this should be noted on 
the Study Termination CRF page and the associated SAE that led to the death must be 
reported.  
Withdrawal of consent  
The subject can withdraw consent for participation in the study at any time without penalty 
or loss of benefit to which the subject is otherwise entitled. Reason for early termination 
should be deemed as “withdrawal of consent” if the subject withdraws from participation 
due to a non-medical reason (i.e., reason other than AE). If the subject intends to withdraw 
consent from the study, the investigator should clarify if the subject will withdraw 
completely from the study or if the subject will continue study participation for safety, or a 
subset of other study procedures. If the subject requests complete withdrawal from the 
study, no further study interventions will be performed with the subject.  
Lost to Follow-Up  
For subjects who fail to show up for final visits (clinic or telephone contacts), or for three 
consecutive visits, study staff are encouraged to make at least three documented attempts 
to contact the subject by telephone and at least one documented written attempt to contact 

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the subject to encourage the completion of study termination procedures. These efforts to 
contact the subject should be recorded in the source document. The termination date for the 
subject to be captured on the Study Termination CRF page is the date of the last successful 
contact (clinic visit or telephone) with the subject.  
Administrative Reason  
Examples for subjects withdrawn from the study due to administrative reason can include: 
Sponsor decision to terminate the study, subject meeting a pre-specified withdrawal 
criterion, subject discontinuation for insurance issues, moving, no time, etc. This reason 
should be noted in the Study Termination CRF page and any ongoing AEs at the time of 
study withdrawal must be followed until resolution/stabilization.  
If the clinical study is prematurely terminated by the Sponsor, the investigator is to promptly 
inform the study subjects and local EC/IRB and should assure appropriate therapy and 
follow up for the subjects. All procedures and requirements pertaining to the archiving of 
study documents should be followed. All other study materials (study medication/vaccines, 
etc.) must be returned to the Sponsor.  
For subjects who are withdrawn from the study due to receipt of an excluded 
medication/vaccination or due to significant protocol non-compliance, this reason should 
be noted in the Study Termination CRF page.  
Subjects should submit the diary card data at day 8 (visit 2). Subject must be contacted by 
phone if they fail to submit the diary card on visit 2 and proper arrangement be made for 
collection of dairy.  
Protocol Deviation  
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. In general, subjects associated with protocol deviations may 
remain in the study unless continuation in the study jeopardizes the subject’s health, safety, 
or rights.  
Investigators will apply due diligence to avoid protocol deviations. Under no circumstances 
should the investigator contact GSK or its agents, if any, monitoring the study to request 
approval of a protocol deviation, as no authorized deviations are permitted. If the 
investigator feels a change to the protocol would improve the conduct of the study this must 
be considered a protocol amendment, and unless such an amendment is agreed upon by 
GSK and a substantial amendment is approved by the IRB/EC and health authorities it 
cannot be implemented.   
Any subject who becomes pregnant during the study, despite the protocol requirement for 
adequate contraception, should be encouraged to continue participating in the study for 
safety follow-up. The site must complete a Pregnancy Report CRF (initial report) as soon 

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as possible after learning of pregnancy occurrence (see section 7.1.6, Pregnancies for 
further details). If the subject withdraws from the study for any of the above categories 
except death, the site will obtain permission from the subject to continue to remain in 
contact with her until the outcome of the pregnancy is known, even if the outcome is not 
known until after the subject reaches the end of follow-up period.  
3.9  
End of Study  
Evaluation of the primary and/or secondary immunogenicity objectives requires the testing 
of biological samples from the study subjects, which can only be completed after all 
samples are collected. The last samples for the analysis of the primary and/or secondary 
objectives will be taken at visit 5.   
For the purpose of this protocol, end of study (EoS) is defined as the completion of the 
testing of such biological samples, to be achieved no later than 8 months after collection of 
the last biological sample visit.  
4. 
SELECTION OF STUDY POPULATION  
4.1  
Inclusion Criteria  
In order to participate in this study, all subjects must meet ALL of the inclusion criteria 
described. Are included:  
1. 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.  
2. 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.  
3. Individuals in good health as determined by the outcome of medical history, physical 
examination, hematological blood tests and clinical judgment of the investigator.  
4. 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.   
5. Individuals affiliated to a social security regimen.  
  
4.2  
Exclusion Criteria 
Are excluded:  

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1. 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.    
2. Individuals with any progressive or severe neurological disorder, seizure disorder or 
Guillain-Barré syndrome.  
3. Individuals who are not able to understand and to follow all required study procedures 
for the whole period of the study.  
4. 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.  
5. Progressive, unstable or uncontrolled clinical conditions.  
6. Hypersensitivity, including allergy, to any component of vaccines, medicinal products 
or medical equipment whose use is foreseen in this study.  
7. Individuals with a known bleeding diathesis, or any condition that may be associated 
with a prolonged bleeding time.  
8. Clinical conditions representing a contraindication to intramuscular vaccination and 
blood draws.  
9. Abnormal function of the immune system resulting from:  
• 
Clinical conditions;  
• 
Systemic administration of corticosteroids (PO/IV/IM) 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.   
10. Received immunoglobulins or any blood products within 180 days prior to informed 
consent.  
11. Study personnel as an immediate family or household member.  
12. 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.  
13. 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.  
14. 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.  

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15. Individuals who have received blood, blood products, and/or plasma derivatives 
including parenteral immunoglobulin preparations in the past 180 days.  
16. Individuals with body temperature > 38.0 degrees Celsius within 3 days of intended 
study vaccination.   
17. Individuals with Body Mass Index (BMI)> 30 kg/m2.  
18. Individuals with history of substance or alcohol abuse within the past 2 years.   
19. 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.  
20. Females with history of stillbirth, neonatal loss, or previous infant with anomaly.  
21. Individuals who have a previously laboratory confirmed or suspected disease caused by 
S. sonnei.  
22. Individuals who have had household contact with/and or intimate exposure to an 
individual with laboratory confirmed S. sonnei.  
23. 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.  
24. Individuals with a neutrophil count value lower than 1.8 109/L at screening assessment.  
25. Individuals with human leukocyte antigen (HLA)-B27 positive and/or with history of 
reactive arthritis.  
26. Previous history of Benign Ethnic Neutropenia or drug related Neutropenia and/or 
concomitant treatment with neutropenic agents.  
  
4.3  
Criteria for Delay of Vaccination  
There may be instances when individuals meet all eligibility criteria for vaccination yet 
have a transient clinical circumstance which may warrant delay of vaccination: body 
temperature elevation (≥ 38.0 °C within 3 days prior to intended study vaccination), or use 
of antipyretics and/or analgesic medications within 24 hours prior to vaccination. Under 
such circumstances, a subject may be considered eligible for study enrolment after the 
appropriate window for delay has passed and inclusion/exclusion criteria have been 
rechecked, and if the subject is confirmed to be eligible.  
 

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5. 
STUDY PROCEDURES  
The sections that follow provide an overview of the procedures that are to be followed in 
enrolling, evaluating, and following subjects who participate in this clinical study. Visits 
can be either clinic visits or safety follow-up telephone calls, as specified in the Table below 
and in the Time and Events Table 2.  
Table 5 Study Procedures  
Visit Category  
Procedures  
Pre-vaccination Clinic Visit(s)  
Section 5.1 describes procedures to be followed prior 
to study vaccination: informed consent, screening, 
enrolment, and randomization  
Vaccination Clinic Visit(s)  
Section 5.2 describes procedures to be followed 
during each clinic visit involving vaccination: 
vaccination, 
post-vaccination 
procedures, 
and 
postvaccination reminders   
Post-vaccination Visit(s)   
Section 5.3 describes follow-up clinic visits and 
safety follow-up calls  
Unscheduled Visit(s)  
Section 5.4 describes possible procedures to be 
followed at unscheduled clinic visit  
Study Termination Visit  
Section 5.5 describes procedures to be followed at the 
last study visit for a subject (may include early 
termination visit)  
  
5.1 
Pre-vaccination Clinic Visit(s)  
This section describes the procedures that must be performed for each potential subject 
prior to vaccination, including obtaining informed consent, screening, enrolment and 
randomization.  
5.1.1 Informed Consent/Assent  
"Informed consent" is the voluntary agreement of an individual or his/her legal guardian(s) 
to participate in research. Consent must be given with free will of choice, and without undue 
inducement. The individual must have sufficient knowledge and understanding of the 
nature of the proposed research, the anticipated risks and potential benefits, and the 
requirements of the research to be able to make an informed decision.  
Informed consent following local IRB/EC guidance must be obtained before conducting 
any study-specific procedure (i.e., all of the procedures described in the protocol). The 
process of obtaining informed consent should be documented in the subject source 
document in addition to maintaining a copy of the signed and dated informed consent. 
Additional specifics regarding the informed consent processes are located in section 13.2, 
Informed Consent Procedures.  

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5.1.2 Screening  
Subject identification numbers will be assigned sequentially to the subjects who have 
consented to participate in the study. The eligibility of the subject will be determined based 
on the inclusion and exclusion criteria listed in section 4, Selection of Study Population and 
evaluated during this screening procedure.  
Prior to study enrolment, demographic data will be collected from the subject, including: 
age, gender, race and body mass index.  
Medical history will also be collected, including but not limited to any medical history that 
may be relevant to subject eligibility for study participation such as prior vaccinations, 
concomitant medications, and previous and ongoing illnesses or injuries. Subject who 
participated in the H03_01TP parent trial will have their medical history since the last visit 
reviewed. Relevant medical history can also include any medical history that contributes to 
the understanding of an adverse event that occurs during study participation, if it represents 
an exacerbation of an underlying disease/pre-existing problem.  
Review of systems is a structured interview that queries the subject as to any complaints 
the subject has experienced across each organ system. This will be performed before 
enrolment and used to guide physical examination.  
Important prior and concomitant medications or vaccinations taken prior to start of study 
should be collected (refer to section 6.5, Prior and Concomitant Medications and Vaccines 
for further details).  
Vital signs: heart rate, respiratory rate, diastolic and systolic blood pressure, temperature 
and also anthropometric measurements: height and weight will be collected  
A general physical examination is to be performed by a qualified health care practitioner. 
“Qualified health care practitioner” refers to any licensed health care professional who is 
permitted by institutional policy to perform physical examinations and who is identified 
within the Study Staff Signature Log.  
These data will be written in the source document (see section 9.1, Source Documentation).  
Approximately 15 mL of blood will be obtained as part of the initial screening for 
hematology and serology testing (HIV, hepatitis B and C) and 25 mL for the same tests and 
HLA-B27 for naïve subjects. Another 20 mL of blood will be collected before vaccination 
on day 1 for baseline immunological testing (Refer to section 3.5, Collection of Clinical 
Specimens).  
In the event that the individual is determined ineligible for study participation, he/she is 
considered a screen failure. The reason for screen failure must be documented in the 

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Screening and Enrolment log. If the individual is determined to be eligible for the study, 
he/she will be enrolled into the study.  
5.1.3  Enrolment  
After signing the informed form, if an individual is determined to be eligible for study 
participation, the investigator will enroll the subject.   
5.1.4  Randomization  
5.1.4.1 Randomization  
This is a non-randomized study which is an extension of H03_01TP study done on the same 
setting. Enrolled subjects will be manually assigned a unique Subject ID; since 24 subjects 
to be enrolled are from the previous study (H03_01TP) database, so these will preserve 
their subject ID if they get enrolled. The subsequent 26 new recruits as explained on section 
3.1 overview of study design will be assigned subject ID following the same order used in 
H03_01TP but starting from where last subject’s ID ended. This will easier identify subjects 
who are on booster vaccine dose from subjects given one vaccine dose as per this study. 
The Subject ID will be the subject’s unique identification number for all CRFs and 
associated study documentation that will be used for duration of the study. The Screening 
Number ceases to be used and remains in the Screening and Enrolment Log.   
If for any reason, after enrolment the subject fails to undergo treatment/study procedures 
this is an Early Termination and the reason should be recorded in source document as 
specified in the Source Documentation Agreement Form (SDAF). The information on these 
Early Termination subjects should be kept distinct in the source documentation from 
subjects who are screen failures, as described in section 5.1.2, Screening.  
5.2  
Vaccination Clinic Visit(s)  
The vaccination will be performed on study day 1.  
Ensure all serology samples are taken prior to vaccination.  
Perform pregnancy testing in women of childbearing age (section 3.5, Collection of Clinical 
Specimens for guidance regarding the procedure). Informed consent process with any 
women of childbearing potential will include counseling about pregnancy including 
discussion of their commitment to practice acceptable birth control measures (defined as 
oral, injected or implantable contraceptives).Women of childbearing potential are defined 
as a post onset of menarche and pre-menopausal female capable of becoming pregnant. 
This does not include females who meet any of the following conditions: (1) menopause at 
least 2 years earlier, (2) tubal ligation at least 1 year earlier, (3) total hysterectomy or (4) 
post bilateral oophorectomy.     

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After completing the pre-vaccination procedures on day 1, administer the vaccine to the 
subject according to the procedures described in section 6.3, Vaccine Preparation and 
Administration.  
Prior to administration of vaccination, confirm that the subject is eligible for study 
vaccinations 
by 
checking 
his/her 
medical 
history, 
clinical 
examination, 
all 
inclusion/exclusion criteria and that the subject does not meet any criteria for delaying study 
vaccinations as described in section 4, Selection of Study Population  
5.2.1  Post-vaccination Procedures  
The following post-vaccination procedures will be performed on day 1:   
After vaccination, the subject will be observed for at least 4 hour including observation for 
unsolicited adverse events, solicited adverse events, and body temperature and vital signs 
measurement. Record all safety data collected during this time in the subject’s source 
document.  
A Subject Diary will be used in this study to document solicited adverse events. The Subject 
Diary is the only source for collection of these data; therefore, it is critical that the subject 
completes the Subject Diary correctly. The subject should be trained on how and when to 
complete each field of the Subject Diary.  
Subject Diary training should be directed at the individual(s) who will perform the 
measurements of adverse events and who will enter the information into the Subject Diary.  
The same individual should complete the Subject Diary throughout the 7 days following 
vaccination.  
Training of the subject on how to measure an injection site reaction should be performed 
while the subject is under observation after vaccination. The subject must understand that 
timely completion of the diary card on a daily basis is a critical component to study 
participation. The subject should also be instructed to write clearly and to complete the 
diary card in pen. Any corrections to the diary card that are performed by the person 
completing the diary card should include a single strikethrough line with a brief explanation 
for any change. No changes can be made to the diary card when it is returned to the clinic.  
Starting on the day of vaccination, the subject will check in the evening for specific types 
of reactions at the injection site (solicited local reactions), any specific generalized 
symptoms (solicited systemic reactions), body temperature (taken preferably orally) any 
other symptoms or change in the subject’s health status, and any medications taken 
(excluding vitamins and minerals).   

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The subject should be trained on how to self-measure local solicited adverse events and 
body temperature. The measurement of solicited local adverse events is to be performed 
using the ruler provided by the site.  
Body temperature measurement is to be performed using the thermometer provided by the 
site. If the subject feels unusually hot or cold during the day, the subject should check body 
temperature. If the subject has fever, the highest body temperature observed that day should 
be recorded on the Diary Card. The collection of body temperature, solicited local adverse 
events, solicited systemic adverse events will continue for a total of 7 days on the Diary 
Card. Unsolicited adverse events and medications will be collected by the site staff on the 
source document at the next planned visit based on subject’s interview or when reported by 
the subject to the site staff by phone/unplanned visits.  
At the end of the observation period, the site should schedule the next study visit with the 
subject. The subject will receive a study ID card to be used as a written reminder of the next 
planned study activity and to provide study staff contact details. The subject will be 
reminded to complete the Diary card daily and to contact the site if there are any questions 
and to contact the site immediately (or as soon as the subject is medically stable) if the 
subject has a medical condition that leads to a hospitalization or an emergency room visit.  
The site staff/doctor should instruct the subject to contact the study doctor immediately in 
case of fever. All subjects presenting with a history of fever or any other sign or symptom 
judged by the investigator to be as a result of an infection within 21 days of vaccination 
will have a blood sample collected for a complete blood count to establish the absolute 
neutrophil count. If there is a neutropenia, the subject will be managed appropriately 
according to local and international requirements.   
5.2.2  Post-vaccination Reminders  
Reminder calls (or emails) are not intended to be an interview for collection of safety data. 
If the subject wishes to describe safety information, this information should only be 
collected by a healthcare professional at the site, and the safety data described must be 
written down in the subject’s medical chart/source document.  
Subject Diary Reminder Calls / Emails  
Subject Diary reminder calls will be performed or email will be sent on day 3 and day 7 
post vaccination. The purpose of this call or email is to remind the subject about completion 
of the Subject Diary. The call/email follow the Subject Diary Reminder Telephone 
Call/Email Scripts provided to the site. The subject should be reminded to contact the site 
via the telephone number provided in the informed consent to discuss medical questions. 
The safety data described by the subject on a telephone call must be written down in source 
documents and the subject should be reminded to write the information down in the diary 
card, as applicable.  

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If the email is printed by study staff to document that the reminder was sent, all personal 
information such as name and email address of the subject, will be removed before printing.  
5.3  
Post-vaccination Visit(s)  
5.3.1  Follow-up Clinic Visit(s)  
Safety follow-up clinic visits will be performed on day 8, day 15, day 29 and day 85.  
During visit 2, the Subject Diary will be reviewed. No changes to the information recorded 
within the Subject Diary are permissible. For details on the Subject Diary see sections 3.4.2, 
Tools Used for Data Collection and 5.2.1, Post-vaccination Procedures. The subject will be 
interviewed to determine if any unsolicited adverse events occurred and if any concomitant 
medications or vaccines were taken or received in the time since the last visit. This 
interview will follow a checklist which will facilitate the collection of relevant safety 
information. The healthcare professional reviewing these data will discuss the symptoms 
(if any) reported by the subject and will determine if any additional diagnoses and/or 
adverse events are present. Adverse events reported by the subject at this follow-up clinic 
visit must be recorded in the subject's source document and on an Adverse Events eCRF, 
as specified in section 7.1, Safety Assessment, and not written on the checklist used for the 
interview.  
Perform a brief symptom-directed physical examination if necessary according to 
symptoms the subject has reported. This is a physical examination that will include an 
examination of organ systems that are relevant to the investigator based on review of the 
subject’s reported adverse events, concomitant medication use. The physical assessment 
must be performed by the investigator or designee of the investigator, who is qualified to 
perform a physical assessment in accordance with their institutional policy. Corresponding 
information is documented in the subject’s source document.  
The site should schedule the next study activity, i.e. the next clinic visit and reminder phone 
call/email with the subject. The subject will be reminded to contact the site if there are any 
questions and to contact the site immediately (or as soon as the subject is medically stable) 
if the subject has a medical condition that leads to a hospitalization or an emergency room 
visit.  
5.3.2  Safety Follow-up Calls  
No safety follow up call will be made in this study. 5.4 
 Unscheduled Visits  
An unscheduled visit describes a non-routine study visit triggered by a specific event. These 
could include anticipated or unanticipated adverse events or interventions.  Data obtained 
from such unscheduled visit should be record in a respective source document and eCRF. 

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If a case of neutropenia is observed after vaccination and still prevalent on a subsequent 
visit, the results will be recorded in the Unscheduled Lab eCRF.   
All individuals with a neutropenia, occurring at any time during the study, will have 
additional blood draws for complete blood count to be repeated on a weekly basis until the 
neutropenia resolves. If neutropenia occurs at the subject’s last study visit, the complete 
blood count will be repeated on a regular basis until resolution. For classification of 
neutropenia during the trial, refer to section 7.1.4.1 Adverse Events of Special Interest.  
5.5  
Study Termination Visit  
The study termination visit will occur on day 85 (visit 5). The date of termination is the date 
of the last contact (clinic visit or telephone call) in which the subject’s health status was 
assessed or, in cases where the subject does not agree to any further safety follow-up; it is 
the date consent is withdrawn. This date should be recorded on the termination eCRF page. 
For visit procedures to be performed for a subject whose planned study participation ends 
prematurely, please see section 5.5.1, Early Termination Visit.  
At the clinic visit or during the telephone call, the following procedures will be performed:   
Review of systems, interview of subject to collect: medically attended adverse events, AEs 
leading to withdrawal, SAEs, AESIs, and new onset of chronic disease, interview of subject 
to collect concomitant medications in relation to these events, vaccinations, symptom-
directed physical assessment and a check of general appearance, blood sampling for safety 
laboratory assessment (hematology testing) and immunogenicity, and a urine pregnancy 
test for women of childbearing potential.  
The site will review with the subject the plan of when information relating to the subject’s 
participation in the study may be available (i.e., study results, treatment assignments).  
The site will complete the termination eCRF page and this will mark the completion of the 
subject’s participation in the study.  
5.5.1  Early Termination Visit  
When a subject is withdrawn from treatment or withdraws from the study, the investigator 
will notify the Sponsor and, when possible, will perform the procedures listed below. The 
reason(s) for the early termination will be included in the subject’s source documentation. 
If the Early Termination Visit is a telephone call, collect as much information as possible. 
Early Termination Visits include subjects who were enrolled but not treated.  
At the clinic visit, the following procedures will be performed;   
• 
Review of subject’s medical records, source document and Diary Card,   

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• 
Review of systems, interview of subject to collect unsolicited adverse events, medically 
attended adverse events, AEs leading to withdrawal, SAEs, AESIs, and new onset of 
chronic disease,   
• 
Interview of subject to collect concomitant medications/vaccinations,   
• 
Symptom-directed physical assessment including measurement of vital signs and a 
check of general appearance,   
• 
Blood sampling for safety laboratory assessment (no blood for immunogenicity 
assessment should be obtained unless this is agreed in advance with the Sponsor),   
• 
Urine sample for pregnancy testing.  
All individuals with neutropenia either ongoing or with onset at last study visit will have 
additional blood draws for complete blood count to be repeated on a regular basis until the 
neutropenia resolves (for classification of neutropenia during the trial, refer to section 
7.1.4.1 Adverse Events of Special Interest). Laboratory results obtained after study 
termination will be maintained in subject medical records and not entered in the eCRF.  
The site will review with the subject the plan of when information relating to the subject’s 
participation in the study may be available (e.g., study results, treatment assignments). It 
will also be discussed how information relating to the subject’s participation in the study 
will be shared with the subject’s healthcare provider, if the subject chooses to share this 
information.  
The site will complete the termination CRF page and this will mark the completion of the 
subject’s participation in the study.  
6. 
TREATMENT OF SUBJECTS  
All vaccines associated with this study are to be stored separately from other vaccines and 
medications in a secure location under appropriate storage conditions with temperature 
monitoring. All vaccines associated with this study must be checked for expiration date 
prior to use. Expired vaccines must not be administered to subjects.  
6.1  
Study Vaccine(s)  
The term ‘study vaccine’ refers to those vaccines provided by the Sponsor, which will be 
evaluated as part of the study objectives. The study vaccine specific to this study is GVGH 
S. sonnei 1790GAHB vaccine. The GVGH GAHB-Placebo will be used as diluent for 
bedside mixing as described below.  
The investigational agent is the GVGH S. sonnei vaccine. The vaccine consists of S.  
sonnei 1790-GMMA (200 μg/mL, measured by protein content) adsorbed to Alhydrogel®, 
(0.7 mg Al3+/mL) in Tris-buffered saline. The vaccine does not contain any preservative 
and is available as a liquid formulation in single dose vials with 0.7 mL of injectable 

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solution containing approximately 140 μg of GMMA (as protein content), adsorbed onto 
0.49 mg Al3+. It should be stored at +2/+8 °C.   
A diluent, named GAHB-Placebo, visually matching the S. sonnei 1790GAHB vaccine, is 
also supplied for use in this clinical study as a diluent for bedside mixing.  It contains the 
same formulation ingredients as the active S. sonnei 1790GAHB vaccine, except for the 
Drug Substance antigen 1790-GMMA, and is provided in the same primary packaging as 
the S. sonnei 1790GAHB vaccine.  
  
Aluminum hydroxide is well characterized and used as adjuvant in several licensed 
vaccines. In 1790GAHB, aluminum hydroxide is used as an adsorbent to reduce the 
reactogenicity of LPS and does not enhance the immunogenicity of the GMMA vaccine. 
For further information of study vaccines refer to the Investigator Brochure. 6.2 Non-Study 
Vaccines  
There will be no non-study vaccines to be used.  
6.3  
Vaccine Preparation and Administration  
The investigator or designee will be responsible for oversight of the administration of 
vaccine to subjects enrolled in the study according to the procedures stipulated in this study 
protocol. All vaccines will be administered only by personnel who are qualified to perform 
that function under applicable local laws and regulations for the specific study site.  
Detailed vaccine preparation and administration instructions will be provided to 
investigators in the bedside mixing checklist and instructions prior to study start.  
A S. sonnei 1790GAHB vaccine volume of 0.5 mL will be administered intramuscularly 
after bedside mixing to make a 25 μg protein/0.5 mL dose. Bedside mixing, possibly 
necessary additional labeling of clinical study materials at the study site and vaccine 
administration will be performed according to Sponsor instructions and by trained site staff. 
The site staff responsible for these activities will be personnel who are respectively 
qualified according to applicable local laws and regulations. Sponsor will provide specific 
procedures and training for these activities.    
PRECAUTIONS TO BE TAKEN IN ADMINISTERING STUDY VACCINE:  
Prior to vaccination, subjects must be determined to be eligible for study vaccination and it 
must be clinically appropriate in the judgment of the investigator to vaccinate. Eligibility 
for vaccination prior to first study vaccine administration is determined by evaluating the 
entry criteria outlined in protocol sections 4.1, Inclusion Criteria and 4.2, Exclusion 
Criteria.  
Study vaccines should not be administered to individuals with known hypersensitivity to 
any component of the vaccines.  

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Standard immunization practices are to be observed and care should be taken to administer 
the injection intramuscularly. Before administering vaccine, the vaccination site is to be 
disinfected with a skin disinfectant (e.g., 70% alcohol). Allow the skin to dry. DO NOT 
inject intravascularly.  
As with all injectable vaccines, trained medical personnel and appropriate medical 
treatment should be readily available in case of anaphylactic reactions following vaccine 
administration. For example, epinephrine 1:1000, diphenhydramine, and/or other 
medications for treating anaphylaxis should be available.  
6.3.1 Replacement of unusable vaccines  
In addition to the vaccine doses provided for the planned number of subjects (including 
extra doses to allow flexibility in enrolment at the different sites), at least 5% additional 
vaccine doses will be supplied to replace those that are unusable.   
6.4  
Vaccine Administration Error or Overdose of Vaccine  
Vaccine administration error is defined as receiving a dose of study vaccine that was not 
prepared according to bedside mixing instructions or administered by a different route from 
the intended route of administration. An overdose of study vaccine (whether accidental or 
intentional) is defined when a dose higher than dose foreseen in this clinical study, i.e. 25 
µg is administered in one dose of Shigella sonnei 1790GAHB study vaccine subjects.  
Any vaccine administration error or overdose of study vaccine detailed in this protocol must 
be reported as an adverse event, and if the vaccine administration error or overdose is 
associated with a serious adverse event, it must be reported as such within 24 hours to the 
Sponsor.  
6.5  
Prior and Concomitant Medications and Vaccines  
All relevant medications taken or received by the subject within 4 weeks prior to the start 
of the study are to be recorded on the Prior and Concomitant Medications eCRF.  
In addition, the following are considered prior medications for this protocol:   
all medication/vaccines described in the inclusion and exclusion criteria of this protocol 
including the use of antipyretics and/or analgesic medications within 24 hours prior to 
vaccination and ending 12 hours after vaccination must be identified and the reason for 
their use (prophylaxis versus treatment) must be described in the source document and 
Concomitant Medications CRF Section 4.3, Criteria for Delay of Vaccination. Use of 
antipyretic, 24 hours before vaccination is a reason to delay vaccination.  
Medications taken for prophylaxis are those intended to prevent the onset of symptoms. 
Medications taken for treatment are intended to reduce or eliminate the presence of 
symptoms that are present.  

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Concomitant 
medications 
include 
all 
medications 
(including 
vaccines) 
taken 
by/administered to the subject at and after enrolment and must be documented on the 
Concomitant Medications CRF.  
When recording concomitant medications/vaccines, they should be checked against the 
study entry and continuation criteria in section 4, Selection of Study Population to ensure 
that the subject should be enrolled/continue in the study.  
6.6  
Vaccine Supply, Labeling, Storage and Tracking  
Detailed vaccine supply, labeling, storage and tracking instructions will be provided to 
investigators prior to study start.  
The Sponsor will ensure the following:  
• 
Supply the study vaccine.  
• 
Appropriate labeling of all study that complies with the country legal requirements.  
The investigator must ensure the following:  
• 
Acknowledge receipt of the study vaccines by a designated staff member at the site, 
including confirmation that the vaccines were received in good condition.  
• 
Proper storage of the study vaccines, including:  
- 
Storage in a secure, locked, temperature-controlled location.  
- 
The study vaccine must be stored at the respective label storage temperature 
conditions in a safe and locked place. Access to the storage space should be limited 
to authorized study personnel. The storage conditions will be assessed during pre-
study activities under the responsibility of the sponsor study contact.  
- 
Proper storage according to the instructions specified on the labels.  
- 
Appropriate record keeping and inventory of the study vaccines, including regular 
documentation of adequate storage temperature.  
- 
The storage temperature should be continuously monitored with calibrated (if not 
validated) temperature monitoring device(s) and recorded.   
- 
Temperature excursions must be reported in degree Celsius.  
- 
Any temperature excursion outside the range of +2.0 to +8.0 °C impacting 
investigational medicinal products (IMPs) must be reported to the Sponsor. The 
impacted IMPs must not be used and must be stored in quarantine at label 
temperature conditions until usage approval has been obtained from the Sponsor.  
• 
Appropriate use of the study vaccines, including:  
- 
Use only in accordance with the approved protocol.  

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- 
Proper handling, including confirmation that the vaccine has not expired prior to 
administration.  
- 
Appropriate documentation of administration of vaccines to study subjects 
including:  
▪ Date, dosage, batch/lot numbers, expiration dates, unique identifying numbers 
assigned to subjects and study vaccines, and time of vaccine administration. 
This information will be maintained in an accountability log that will be 
reviewed by the site monitor.  
▪ Reconciliation of all vaccines received from the Sponsor. Reconciliation is defined 
as maintaining records of which and how many vaccines were received, which 
vaccines were administered to subjects, which vaccines were destroyed at the 
site, and which vaccines were returned to the Sponsor, as applicable.  
• 
Proper adherence to the local institutional policy with respect to destruction of study 
vaccines.  
• 
Complete record keeping of vaccine use, wastage, return or destruction, including 
documentation of:  
- 
Copy of the site’s procedure for destruction of hazardous material. -  
Copy 
of Destruction Certificate.  
Vaccines that have been stored differently from the manufacturer’s indications must not 
be used unless the Sponsor provides authorization for use. In the event that the use cannot 
be authorized, the Sponsor will make every effort to replace the vaccine supply. All 
vaccines used in conjunction with this protocol must be stored separately from normal 
hospital/practice stocks to prevent unintentional use of study vaccines outside of the clinical 
study setting.  
Monitoring of vaccine accountability will be performed by the study monitor during site 
visits and at the completion of the study.  
At the conclusion of the study, and as appropriate during the course of the study, the 
investigator must ensure that all unused study vaccines, packaging and supplementary 
labels are destroyed locally (upon approval from the Sponsor) or returned to the Sponsor.  
7. 
ASSESSMENTS  
7.1  
Safety Assessment  
The measures of safety used in this study are based on previous study data. They include a 
close vigilance for, and stringent reporting of selected local and systemic adverse events 
routinely monitored in vaccine studies as indicators of reactogenicity.  

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An adverse event (AE) is defined as any untoward medical occurrence in a subject or 
clinical investigation subject administered a pharmaceutical product at any dose that does 
not necessarily have to have a causal relationship with this treatment. Therefore, an AE can 
be any unfavorable and unintended sign (including an abnormal laboratory finding, for 
example), symptom, or disease temporally associated with the use of an investigational 
product, whether or not considered related to the investigational product. This definition 
includes intercurrent illnesses or injuries and exacerbation of pre-existing conditions.  
For the purpose of this trial, AEs will be from the time the subject signs informed consent 
until Visit 4. AEs occurring after the informed consent form is signed but prior to receiving 
study vaccine will be documented as an adverse event and recorded within source 
document. However, any AEs occurring prior to receipt of any study vaccine will be 
analyzed separately from “treatment emergent” AEs (AEs occurring after administration of 
the first study vaccine). All adverse events that are serious, clinically significant as judged 
by the investigators, medically attended and AESI will be collected until study termination 
at visit 5.  
Adverse events are collected as either solicited or unsolicited adverse events. Solicited 
events are derived from organized data collection systems, such as Subject Diaries or 
interview.  
7.1.1  Solicited Adverse Events  
The term “reactogenicity” refers to solicited signs and symptoms (“solicited adverse 
events”) occurring in the hours and days following a vaccination, to be collected by the 
subject for 7 consecutive days, using a pre-defined Subject Diary.  
The following solicited adverse events are included in the Subject Diary. Each adverse 
event is to be assessed using the scoring system reported in parentheses below:   
Solicited Local Adverse Events  
These include erythema, induration and pain at injection site. They will be assessed using 
the scoring system reported in a table below.  Table 6 Grading of solicited local adverse 
events  
Solicited local adverse 
events  
Grade 0 
Absent  
Present - Grading of Severity  
 
Grade 1 Mild  
Grade 2 
Moderate  
Grade 3 
Severe  
Injection site Erythema  
(Captured as 
measurements in 
millimeters)  
1-24 mm  
25-50 mm  
51-100 mm  
> 100 mm  

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Injection site Induration  
(Captured as 
measurements in 
millimeters)  
1-24 mm  
25-50 mm  
51-100 mm  
> 100 mm  
Injection site Pain  
No pain  
Present but does not 
interfere 
with 
activity  
Interferes with 
activity  
Prevents daily 
activity  
Solicited Systemic Adverse Events  
These include headache, arthralgia, chills, fatigue, malaise, myalgia, and fever (body 
temperature measured orally). They will be assessed using the scoring system reported in a 
table below.  
Table 7 Grading of solicited systemic adverse events  
Solicited 
adverse events  
systemic  Grade 0 
Absent  
Present - Grading of Severity*  
Grade 1 Mild  
Grade 2 
Moderate  
Grade 3 
Severe  
Headache  
No headache  Present but does not 
interfere 
with 
activity  
Interferes with 
activity  
Prevents daily 
activity  
Arthralgia  
No  
arthralgia  
Present but does not 
interfere 
with 
activity  
Interferes with 
activity  
Prevents daily 
activity  
Chills  
No chills  
Present but does not 
interfere 
with 
activity  
Interferes with 
activity  
Prevents daily 
activity  
Fatigue  
No fatigue  
No interference with 
activity  
Some  
interference  
Significant; 
prevents daily  
with activity  
activity  
Malaise  
No malaise  
No interference with 
activity  
Some  
interference with 
activity  
Significant; prevents 
daily activity  
Myalgia   
No myalgia  
Present but does not 
interfere with activity  Interferes with 
activity  
Prevents daily 
activity  
Fever as a  
Body temperature 
(Captured as  
measurements in degrees 
Celsius)  
≤ 37.9 °C  
≥ 38.0 – 38.9°C  
≥ 39.0 – 39.9°C  
≥ 40.0°C  
Oral Temperature: <35.5 °C to ≥38.0 °C  
Other Solicited Adverse Events  
These include use of analgesics/antipyretics. It will be assessed using the scoring system 
reported in a table below.  

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Other Solicited adverse 
events  
Grade 0 
Absent  
Present - Grading of Severity  
 
Grade 1 Mild  
Grade 2 
Moderate  
Grade 3 
Severe  
Use of analgesics/ 
antipyretics  
Categorized as “yes” or “no”   
 
The study staff must review the data entered into the Subject Diary as described in section 
3.4.2, Tools Used for Data Collection and section 5.3.1, Follow-up Clinic Visit(s).  
Note: Any solicited adverse event that meets any of the following criteria must be entered 
into subjects’ source document (see section 9.1, Source Documentation) and also as an 
adverse event on the Adverse Event CRF:  
• 
Solicited local or systemic adverse event that continues beyond day 7 after vaccination.   
• 
Solicited local or systemic adverse event that leads to a visit to a healthcare provider 
(medically attended adverse event, see section 7.1.3, Evaluation of Adverse Events).  
• 
Solicited local or systemic adverse event leading to the subject withdrawing from the 
study or the subject being withdrawn from the study by the investigator (adverse event 
leading to withdrawal, see section 7.1.3, Evaluation of Adverse Events).  
• 
Solicited local or systemic adverse event that otherwise meets the definition of a serious 
adverse event (see section 7.1.4, Serious Adverse Events).  
7.1.2  Unsolicited Adverse Events  
An unsolicited adverse event 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. In case of such events, subjects will be instructed to contact 
the site as soon as possible to report the event(s). The detailed information about the 
reported unsolicited AEs will be collected by the qualified site personnel during the 
interview and will be documented in the subject’s records.  
Unsolicited AEs that are not medically attended nor perceived as a concern by subjects will 
be collected during interview with the subject and by review of available medical records 
at the next visit (see section 5.3, Post-vaccination Visit(s)).  
7.1.3  Evaluation of Adverse Events  
Every effort should be made by the investigator to evaluate safety information reported by 
a subject for an underlying diagnosis and to capture this diagnosis as the event in the AE 
page. In other words, the practice of reporting only symptoms (e.g., “cough” or “ear pain”) 

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are better reported according to the underlying cause (e.g., “asthma exacerbation” or “otitis 
media”).  
The severity of events reported on the Adverse Events CRF will be determined by the 
investigator as:  
Mild:  
transient with no limitation in normal daily activity.  
Moderate:  
some limitation in normal daily activity. Severe: 
 unable to perform normal daily activity.  
The relationship of the study treatment to an AE will be determined by the investigator 
based on the following definitions:  
1. Not Related  
The AE is not related to an investigational vaccine if there is evidence that clearly indicates 
an alternative explanation. If the subject has not received the vaccine, the timing of the 
exposure to the vaccine and the onset of the AE are not reasonably related in time, or other 
facts, evidence or arguments exist that reasonably suggest an alternative explanation, then 
the AE is not related.  
2. 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. 3. Probably Related  
Exposure to the investigational vaccine and AE are reasonably related in time and no 
alternative explanation has been identified.  
The relationship of the study treatment to an unsolicited AE will be determined by the 
investigator.   
Note: solicited AEs will not be evaluated for relationship to study treatment. Grading for 
severity of solicited local and systemic AEs is described in section 7.1.1, Solicited Adverse 
Events.  
Adverse events will also be evaluated by the investigator for the co-existence of any of the 
other following conditions:  
• 
“Medically attended adverse event”: an adverse event that leads to a visit to a healthcare 
provider.  
• 
“New onset of chronic disease” (NOCD): an adverse event that represents a new 
diagnosis of a chronic medical condition that was not present or suspected in a subject 
prior to study enrolment.  

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• 
AEs leading to withdrawal: adverse events leading to study or vaccine withdrawal.  
• 
Potential immune-mediated diseases (pIMDs): a subset of AEs that include 
autoimmune diseases and other inflammatory and/or neurologic disorders of interest 
which may or may not have an autoimmune aetiology. In this study, only the pIMDs 
reported in the table below will be collected. However if other pIMDs are discovered 
during development of the vaccine, the table will be revised and updated accordingly.  
Musculoskeletal 
disorders  
Spondyloarthritis, 
including 
ankylosing 
spondylitis, 
reactive arthritis (Reiter's Syndrome) and undifferentiated 
spondyloarthritis   
Blood disorders  
Autoimmune neutropenia   
If solicited or unsolicited adverse events have been reported and the subject indicated that 
the symptoms required medical attendance or were of concern, the subject must be 
contacted for further information.  
When the subject is contacted for any of these reasons, the contact must be documented in 
the subject’s source documentation.  
All AEs, regardless of severity, will be monitored until resolution or until the investigator 
assesses them as chronic or stable. All subjects experiencing AEs - whether considered 
associated with the use of the study vaccine or not - must be monitored until symptoms 
subside and any abnormal laboratory values have returned to baseline, or until there is a 
satisfactory explanation for the changes observed, or until death, in which case a full 
pathologist’s report should be supplied, if possible. The investigator’s assessment of 
ongoing Adverse Events at the time of each subject’s last visit should be documented in the 
subject’s medical chart.  
7.1.4  Serious Adverse Events  
A serious adverse event (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.  

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• 
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.  
Adverse events which do not fall into these categories are defined as non-serious.  
It should be noted that a severe adverse event need not be serious in nature and that a serious 
adverse event need not, by definition, be severe.  
Serious adverse events will be captured both on the Vaccines Serious Adverse Event 
(VSAE) form as well as on the AE CRF. All SAEs will be evaluated by the investigator for 
relationship of the event to study vaccine. SAEs that are judged to be possibly or probably 
related to the study vaccine should be reported to the Sponsor as related events. The 
relationship of the study treatment to an SAE will be determined by the investigator based 
on the following definitions:  
1. Related  
The SAE is judged by the investigator to be possibly or probably related to the study vaccine 
on the AE CRF page (see section 7.1.3, Evaluation of Adverse Events).  
2. Not Related  
The SAE is not related if exposure to the study vaccine has not occurred, or the occurrence 
of the SAE is not reasonably related in time, or the SAE is considered unlikely to be related 
to use of the study vaccine, i.e., there are no facts (evidence) or arguments to suggest a 
causal relationship.  
The relationship of the study vaccine to an SAE will be determined by the investigator.  
In addition, SAEs will be evaluated by the Sponsor or designee for “expectedness.” An 
unexpected AE is one that is not listed in the current Summary of Product Characteristics 
or the Investigator’s Brochure or an event that is by nature more specific or more severe 
than a listed event.  
In addition, a pre-existing event or condition that results in hospitalization should be 
recorded on the Medical History CRF. If the onset of an event occurred before the subject 
entered the study (e.g., any pre-planned hospitalization for conditions like cosmetic 
treatments or for non-emergency routine visits for a pre-existing condition), the 
hospitalization would not lead to an AE being classified as serious unless, in the view of 
the investigator, hospitalization was prolonged as a result of participation in the clinical 
study or was necessary due to a worsening of the pre-existing condition.  
7.1.4.1  
Adverse Events of Special Interest  

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Adverse events of special interest (AESIs) are predefined adverse events that will be 
specifically highlighted to the investigator and will be summarized separately. Only AESI 
meeting the definition of SAE will be categorized and reported as such in this study.  
Reactive arthritis (ReA) or Neutropenia will be collected and analyzed as an AESI for this 
study.   
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.  
For diagnosis of ReA, imaging and aspiration are not required (unless clinically indicated).  
Neutropenia is defined as decrease of neutrophil count asymptomatically or 
symptomatically with ANC <1.8x109/L, occurring at 7 days after vaccination. Its graded 
from grade 1 to 4 basing on neutrophil counts as follows: Grade 1 ANC 1.5-<1.8 x 109 /L, 
Grade 2 ANC <1.5 x 109 /L, Grade 3 ANC 1.0- 0.5 x 109 /L, and Grade 4 <0.5 x 109 /L.  
This is completely diagnosed by laboratory testing for complete blood count.   
7.1.5  Methods for Recording Adverse Events and Serious Adverse Events  
Findings regarding Adverse Events must be reported on an Adverse Events CRF, as 
specified in section 7.1.1, Solicited Adverse Events, and on the VSAE form, if applicable, 
which is part of the Investigator Site File. All findings in subjects experiencing AEs must 
be reported also in the subject's source document.  
All SAEs which occur during the course of the study, whether considered to be associated 
with the study vaccination or not and even if the information is incomplete, must be reported 
within 24 hours of the site becoming aware of the event to the Sponsor. Specific 
instructions and contact details for collecting and reporting SAEs will be provided to the 
investigator. Specifically, once an investigator becomes aware that a SAE has occurred in 
a study subject, the investigator (or designate) must complete a paper expedited Adverse 
Events report and forward it to the Sponsor WITHIN 24 HOURS. The report will always 
aimed to be completed as thoroughly as possible with all available details of the event and 
then dated and signed by the investigator (or designate). Even if the investigator does not 
have all information regarding a SAE, the report should still be completed and forwarded 
to the Sponsor within 24 hours. Once additional relevant information is received, the report 
should be updated and forwarded the Sponsor WITHIN 24 HOURS. The investigator will 
always provide an assessment of causality at the time of the initial report.  

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All SAEs are also to be documented on the Adverse Events CRF. Any medication or other 
therapeutic measures used to treat the AE will be recorded on the appropriate CRF(s) in 
addition to the outcome of the AE.  
Only AESI meeting the definition of SAE will be categorized and reported as serious in this 
study by the investigator within 24 hours. However all other AESI irrespective of their 
grading will be recorded in the adverse event page of eCRF and the source documents.   
After receipt of the initial report, representatives of the Sponsor or its designee will contact 
the investigator if it is necessary to obtain further information for assessment of the event. 
Of note, after the initial AE/SAE report, the investigator is required to proactively follow 
each subject and provide additional relevant information on the subject’s condition to the 
Sponsor (within 24 hours for SAEs and Potential ImmuneMediated Disease pIMD, and 
within 2 weeks for pregnancies).  
All SAEs must be reported by the investigator to his/her corresponding EC/IRB and/or 
applicable regulatory authorities in accordance with institutional policy/regulatory 
requirements and adequate documentation of this notification must be provided to the 
Sponsor.  
GSK or its designee must also comply with the applicable regulatory requirement(s) related 
to the reporting of suspected unexpected serious adverse vaccine reactions (also known as 
SUSARs) to the regulatory authority(ies) and the IRB/EC. If a SUSAR or other safety 
signal relating to use of one of the study vaccines is reported to GSK or its designee, the 
Sponsor will communicate the information to the investigator and the investigator will be 
responsible for submitting this information to the EC/IRB and other relevant authorities.  
7.1.5.1  
Post-Study Events  
Any SAE that occurs outside of the protocol-specified follow-up period and considered to 
be caused by the study vaccine must be reported to the Sponsor. These SAEs will be 
processed by the Sponsor as during the course of the study, until 3 months after last subject 
last visit. Instructions and contact details for collecting and reporting these suspected SAEs 
will be provided to the investigator.  
7.1.6  Pregnancies  
To ensure subjects’ safety, each pregnancy in a subject after study vaccination must be 
reported to the Sponsor in due time of the site learning of its occurrence. If the subject 
agrees to submit this information, the pregnancy must be followed to determine outcome, 
including spontaneous or voluntary termination, details of the birth, and the presence or 
absence of any birth defects, congenital abnormalities, or maternal and/or newborn 
complications. This follow-up should occur even if intended duration of safety follow-up 
for the study has ended.  

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Pregnancy data must be recorded on a Pregnancy Report CRF (initial report) and Pregnancy 
Follow-Up CRF (outcome report) and reported to the Sponsor. Instructions and contact 
details for submitting the Pregnancy CRFs will be provided to the investigator.  
Any pregnancy outcome meeting the definition of a SAE (see section 7.1.4, Serious 
Adverse Events) must also be reported on the VSAE Report Form. The following should 
always be considered as SAE.  
• 
Spontaneous pregnancy loss, including:  
−  spontaneous abortion, (spontaneous pregnancy loss before/at 22 weeks of 
gestation)  
 
−  ectopic and molar pregnancy  
 
−  Stillbirth (intrauterine death of foetus after 22 weeks of gestation).  
Note: the 22 weeks cut-off in gestational age is based on WHO-ICD 10 noted in the 
EMA Guideline on pregnancy exposure (EMA, 2006). It is recognized that national 
regulations might be different.  
• 
Any early neonatal death (i.e. death of a live born infant occurring within the first 7 
days of life).   
• 
Any congenital anomaly or birth defect (as per [CDC MACDP] guidelines) identified 
in the offspring of a study subject (either during pregnancy, at birth or later) regardless 
of whether the foetus is delivered dead or alive. This includes anomalies identified by 
prenatal ultrasound, amniocentesis or examination of the products of conception after 
elective or spontaneous abortion.  
7.1.7  Safety Laboratory Measurements  
For list of safety laboratory measurement, refer to synopsis Table 2, Hematological Safety 
Table 3.  
Safety laboratory measurement will be performed as described in Section 3.5, Collection of 
Clinical Specimens.   
Significant alterations in hematology will be clinically assessed by the investigator’s 
medical judgment based on interpretation of deviations from institution’s normal values.   
Any abnormality in laboratory measurements classified as clinically significant must be 
reported in the Adverse Event CRF form.  
If a subject is to have blood drawn testing for safety laboratory for repeat safety assessment 
(i.e., in case of markedly abnormal safety laboratory parameter), investigator’s medical 
judgment will be applied concerning values that would trigger reanalysis and frequency of 
repeats. If neutropenia is observed at a visit, a complete blood count will be repeated on a 
weekly basis until resolution.  

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Safety laboratory assessments will be performed at the site laboratory, and results of these 
tests will be recorded in the source documents and in the CRF.   
7.2  
Efficacy Assessment  
This study has no efficacy endpoints.  
7.3  
Immunogenicity Assessment  
The ELISA methodology used in this study has been adopted based on scientific consensus 
and has been deemed appropriate to describe the immune response against Shigella sonnei 
GMMA in this study.  
The measure of immunogenicity used in this study is IgG ELISA against Shigella sonnei 
OAg. The serologic assays on clinical samples will be performed at GSK, Clinical Serology 
Laboratory, Marburg, Germany, or a delegated laboratory. Section 3: Study Design.  
For reference of visits the measurements are taken, refer to section 3.5 and to the Clinical 
Specimen Laboratory Manual.   
  
 

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8. 
STATISTICAL CONSIDERATIONS  
8.1 
Endpoints  
8.1.1 Primary Endpoint(s)  
8.1.1.1 
Primary Safety Endpoint(s)  
This study has no primary safety endpoint.   
8.1.1.2 
Primary Efficacy Endpoint(s) This study has no efficacy measurements.  
8.1.1.3 
Primary Immunogenicity Endpoint(s)  
The primary immunogenicity endpoint which is memory response, against the OAg of S. 
sonnei will be evaluated by measuring IgG Geometric mean concentrations (GMCs) after 
vaccination as determined by ELISA with O-antigen containing LPS as coating antigen.  
8.1.2 Secondary Endpoint(s) 8.1.2.1  
Secondary Safety 
Endpoint(s) The measures of safety will include:  
a. Numbers of subjects with deviations from normal values of hematological tests after 
vaccination.  
b. Numbers of subjects with solicited local and systemic reactions during 7 days 
following vaccination. Solicited local reactions include injection site erythema, 
injection site induration and injection site pain; solicited systemic reactions include 
headache, arthralgia, chills, fatigue, malaise, myalgia, and fever (as measured 
orally).  
c. Numbers of subjects with reported unsolicited adverse events (of any nature and 
severity) during 84 days following vaccination.  
d. Number of subjects with reported SAEs throughout the study duration.  
8.1.2.2 
Secondary Efficacy Endpoint(s)  
The study has no secondary efficacy endpoint.  
8.1.2.3 
Secondary Immunogenicity Endpoint(s)  
a. IgG Geometric mean concentrations (GMCs) at 7, 14, 28 and 84 days after 
vaccination as determined by ELISA and applicable geometric mean ratios between 
post vaccination and baseline samples.  
b. Number and percentage of subjects with seroresponse for anti- LPS S. sonnei at 7, 
14, 28 and 84 days after vaccination. Seroresponse is aimed to define a significant 

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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.Number 
and 
percentage 
of 
subjects 
with 
 EU/ml for anti-LPS S. sonnei at c. 
Number and percentage of subjects with titers post vaccination concentration ≥ 
121 EU/ml for anti-LPS S. sonnei at 7, 14, 28 and 84 days after vaccination.  
A post-vaccination concentration ≥ 121 anti-LPS serum IgG units in the GVGH ELISA 
with O-antigen containing LPS as coating antigen corresponds to a titer of 1:800 in the 
ELISA method used by Cohen et al. (1989 J. Clin. Microbiol. 27:162). This antibody level 
is the median antibody concentration of a set of 87 convalescent subjects previously 
infected by S. sonnei. The value of 121 anti-LPS serum IgG units in the GVGH ELISA was 
determined by calibration against the Cohen ELISA (i.e., the GVGH standard serum was 
tested in Cohen’s lab using the Cohen’s methodology).  
The serologic assays on clinical samples will be performed at GSK, Clinical Laboratory 
Science (CLS), Marburg, Germany, or a delegated laboratory.  
 8.1.3 Exploratory Endpoint(s)  
8.1.3.1  
Exploratory Safety Endpoint(s)  
The study has no exploratory safety endpoint(s).  
8.1.3.2  
Exploratory Efficacy Endpoint(s)  
The study has no exploratory efficacy endpoint(s).  
8.1.3.3  
Exploratory Immunogenicity Endpoint(s)  
Other assays, including serum secretory IgA, might be done to further characterize the 
immune response to the study vaccine. The analysis will be described in the statistical 
analysis plan.  
8.2  
Success Criteria  

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The study has no predefined success criteria. 8.2.1 
 Success Criteria for Primary Objective(s) Not 
applicable.  
8.2.1.1  
Success Criteria for Primary Safety Objective(s) 
Not applicable.  
8.2.1.2  
Success Criteria for Primary Efficacy Objective(s) 
Not applicable.  
8.2.1.3  
Success Criteria for Primary Immunogenicity Objective(s) 
Not applicable.  
8.2.2  Success Criteria for Secondary Objective(s) 
Not applicable.  
8.2.2.1  
Success Criteria for Secondary Safety Objective(s) 
Not applicable.  
8.2.2.2  
Success Criteria for Secondary Efficacy Objective(s) 
Not applicable.  
8.2.2.3  
Success Criteria for Secondary Immunogenicity Objective(s) 
Not applicable.  
8.3  
Analysis Sets  
8.3.1  All Enrolled Set  
All screened subjects who provide informed consent and provide demographic and/or 
baseline screening assessments, regardless of the subject’s randomization and treatment 
status in the study and received a Subject ID.  
8.3.2  All Exposed Set  
All subjects in the enrolled set who receive a study vaccination.  
8.3.3  Safety Set  

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Solicited Safety Set (solicited local and systemic adverse events and other solicited 
adverse events)  
All subjects in the Exposed Set with any solicited adverse event data and/or indicators of 
solicited adverse events.  
Unsolicited Safety Set (unsolicited adverse events)  
All subjects in the Exposed Set with unsolicited adverse event data.  
Overall Safety Set  
All subjects who are in the Solicited Safety Set and/or Unsolicited Safety Set.  
8.3.4  Full Analysis Set (FAS) Efficacy/Immunogenicity Set  
Full Analysis Set Efficacy  
Not applicable.  
Full Analysis Set Immunogenicity  
All subjects in the Enrolled Population who:  
▫ Receive a study vaccination AND provide at least one immunogenicity data at relevant 
time points.  
The FAS will be the primary analysis set for the immunogenicity objective.  
In case of vaccination error, subjects in the FAS sets will be analyzed “as randomized” (i.e., 
according to the study group a subject was assigned).  
8.3.5  Per Protocol (PP) Immunogenicity Set  
All subjects in the FAS / Immunogenicity who:  
• 
Correctly receive the vaccine.  
• 
Have no protocol deviations leading to exclusion (see section 8.3.8, Protocol 
Deviations) as defined prior to analysis.  
• 
Are not excluded due to other reasons defined prior to analysis (see section 8.3.8, 
Protocol Deviations).  
PPS are subsets of FAS and should be always defined even if the objectives do not require 
it.  
Examples for subjects excluded due to other reasons than protocol deviations are   
 
-  Subjects who withdrew informed consent.  

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8.3.6  Other Analysis Sets 
None.  
8.3.7  Subgroups Not 
applicable.  
8.3.8  Protocol Deviations  
A protocol deviation is any change, divergence, or departure from the study design or 
procedures of a study protocol. A protocol deviation may be a reason to remove data from 
an analysis set at the time of analysis. CSR-reportable protocol deviations will be defined 
as exclusionary from the analysis according to protocol objectives and endpoints, which 
will be specified in the statistical analysis plan. In some cases exclusion of data may be due 
to a reason other than a protocol deviation, i.e. early termination.  
8.4  
Statistical Analysis Plan  
8.4.1  Analysis of Demographic and Baseline Characteristics  
Descriptive statistics (mean, standard deviation, median, minimum and maximum) for age 
and BMI at enrolment will be calculated overall and by vaccine group.   
Distributions of subjects by sex and ethnic origin will be summarized overall and by vaccine 
group.  
8.4.2  Analysis of Primary Objective(s)  
8.4.2.1  
Analysis of Primary Safety Objective(s) 
The study has no primary safety objective.  
8.4.2.1.1  Analysis of Extent of Exposure  
The frequencies and percentages of subjects with vaccination will be summarized overall 
and by study group. Data will be tabulated for the All Enrolled Set.  
8.4.2.1.2  Analysis of Solicited Local, Systemic and Other Adverse Events  
All solicited adverse events will be summarized according to defined severity grading 
scales.   
Frequencies and percentages of subjects experiencing each adverse event will be presented 
for each symptom severity. Summary tables showing the occurrence of any local or 
systemic adverse event overall and at each time point will also be presented.  

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Post-vaccination solicited adverse events reported from day 1 to day 7 will be summarized 
for the intervals day 1-3, day 4-7, day 1-7 by maximal severity and by vaccine group, 
excluding the 30 minute and 4 hour measurement, which will be summarized separately. 
The severity of solicited local adverse events, including injectionsite erythema and 
induration will be summarized according to categories based on linear measurement: 25 to 
50 mm, 51 to 100 mm, >100mm.  
Injection site pain/tenderness and systemic adverse events (except fever) occurring up to 7 
days after vaccination will be summarized according to “mild”, “moderate” or “severe”.  
Each solicited local and systemic adverse event will also be further summarized as “none” 
versus “any”.  
Implausible measurements (for further definition see statistical analysis plan) will be left 
out of the analysis.  
Use of antipyretics and analgesics will be summarized by frequency, by type of use 
(prophylactic versus treatment) and percentage of subjects reporting use. The influence of 
antipyretics and analgesics use on the occurrence of specific adverse events (e.g., fever, 
pain) will be assessed.  
Body temperature will be summarized by 0.5 °C and 1.0 °C increments from 36.0 °C up to 
≥40 °C.  
8.4.2.1.3  Analysis of Unsolicited Adverse Events  
This analysis applies to all adverse events occurring during the study, judged either as 
probably related, possibly related, or not related to vaccination by the investigator, recorded 
in AE CRF, with a start date on or after the date of vaccination. AE starting prior to the 
vaccination will only be listed. The original verbatim terms used by investigators to identify 
adverse events in the CRFs will be mapped to preferred terms using the MedDRA 
dictionary. The adverse events will then be grouped by MedDRA preferred terms into 
frequency tables according to system organ class.  
All reported adverse events, as well as adverse events judged by the investigator as at least 
possibly related to study vaccine, will be summarized according to system organ class and 
preferred term within system organ class. These summaries will be presented by 
vaccination group and by interval of study observation. When an adverse event occurs more 
than once for a subject, the maximal severity and strongest relationship to the vaccine group 
will be counted.  
Separate summaries will be produced for the following categories:   
• 
Serious adverse events  
• 
Adverse events that are possibly or probably related to vaccine  

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• 
Adverse events of special interest  
• 
New onset of chronic disease  
• 
Potential immune-mediated diseases (pIMDs) adverse event leading to withdrawal • 
Adverse events leading to a medically attended visit  
• 
Adverse event by data source.  
Data listings of all adverse events will be provided by subject. In addition, adverse events 
in the categories above will be provided as listed data.  
8.4.2.1.4  Analysis of Safety Laboratory Values  
The investigator must assess all safety laboratory results (see section 7.1.7). Clinically 
significant modifications in hematology test values will be assessed by medical judgment 
based on interpretation of deviations from the institution’s normal values.  
All laboratory safety data will be analyzed descriptively by study group. Safety laboratory 
data will be shown in a 3 x 3 table by visit using categorization of laboratory according to 
institutional normal reference range (below, within, above).  
 8.4.2.2  
Analysis of Primary Efficacy Objective(s) 
The study has no primary efficacy objective.  
8.4.2.2.1  Statistical Hypotheses  
This Phase 1 safety and immunogenicity trial is aimed to descriptively evaluate the safety 
and immunogenicity profiles of the study vaccines. No specific hypotheses are tested in this 
study.  
 8.4.2.2.2 Analysis Sets  
For more details see (section 8.3 Analysis Sets).  
8.4.2.2.3  
Statistical Methods 
Not applicable.  
8.4.2.3  
Analysis of Primary Immunogenicity Objective(s)  
8.4.2.3.1  Statistical Hypotheses  
This Phase 1 safety and immunogenicity trial is aimed to descriptively evaluate the safety 
and immunogenicity profiles of the study vaccines. No specific hypotheses are tested in this 
trial.  

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8.4.2.3.2  Analysis Sets  
The modified FAS will be the primary analysis set for the immunogenicity objective 
(further details are given in section 8.3, Analysis Sets).  
8.4.2.3.3  Statistical Methods  
Analysis of continuous variables  
The ELISA concentrations will be logarithmically transformed (base10) (to fulfil the 
normal distribution assumption). GMC will be calculated, with their associated two-sided 
95% CIs, by exponentiating the corresponding log-transformed means and their 95% CI.  
Additionally, within-subject GMRs will be computed for GMTs/GMCs at 7, 14, 28 and 84 
days after vaccination versus baseline (day 1). The GMRs and 95% CIs will be constructed 
by exponentiating the mean within-subject differences in log-transformed titers and the 
corresponding 95% CIs. Analysis of binary variables  
 
percentages will be computed.  
Titers below the limit of detection will be set to half that limit for the purposes of analysis. 
Missing values of immunogenicity will be excluded from analyses (i.e. complete-case 
analysis) since they are considered missing completely at random, i.e. not informative and 
with no impact on inferences  
8.4.3  Analysis of Secondary Objective(s)  
8.4.3.1  
Analysis of Secondary Safety Objective(s)  
For more details see Section 8.4.2.1.2 Analysis of Solicited Local, Systemic and Other 
Adverse Events and 8.4.2.1.3 Analysis of unsolicited adverse events.  
8.4.3.1.1  Analysis of Extent of Exposure  
For more details see section 8.4.2.1.1 Analysis of Extent of Exposure.  
8.4.3.1.2  Analysis of Solicited Local, Systemic and Other Adverse Events  
For more details see Section 8.4.2.1.2 Analysis of Solicited Local, Systemic and Other 
Adverse Events.  
8.4.3.1.3  Analysis of Unsolicited Adverse Events  
For more details see 8.4.2.1.3 Analysis of unsolicited adverse events.  

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8.4.3.1.4  Statistical Hypotheses  
For more details see section 8.4.2.2.1, Statistical Hypotheses.  
8.4.3.1.5  Analysis Sets  
For more details see section 8.3, Analysis Sets.  
8.4.3.1.6  Statistical Methods  
For more details see section 8.4.2.2.3, Statistical Methods.  
8.4.3.2  
Analysis of Secondary Efficacy Objective(s) 
The study has no efficacy objective.  
8.4.3.2.1  
Statistical 
Hypotheses Not applicable. 
8.4.3.2.2  
Analysis Sets Not 
applicable.  
8.4.3.2.3  
Statistical Methods 
Not applicable.  
8.4.3.3  
Analysis of Secondary Immunogenicity Objective(s)  
8.4.3.3.1  
Statistical Hypotheses 
Not applicable.  
8.4.3.3.2  Analysis Sets  
For more details see section 8.3, Analysis Sets.  
8.4.3.3.3  Statistical Methods  
For more details see section 8.4.2.2.3, Statistical Methods.  
8.4.4  Analysis of Exploratory Objectives  
8.4.4.1  
Analysis of Exploratory Safety Objective(s) 
Not applicable.  

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8.4.4.2  
Analysis of Exploratory Efficacy Objective(s) 
Not applicable.  
8.4.4.3  
Analysis of Exploratory Immunogenicity Objective(s)  
Other assays, including serum secretory IgA, might be done to further characterize the 
immune response to the study vaccine. The analysis will be described in the statistical 
analysis plan.  
8.5  
Sample Size and Power Considerations of Primary and Secondary Objectives  
No formal statistical sample size and power computations are performed since the 
objectives of the study are to descriptively assess the immunogenicity and safety of the 
investigational vaccine.  
8.6  
Interim Analysis  
No interim analysis of data from this study is planned.  
9. 
SOURCE DOCUMENTATION, STUDY MONITORING AND AUDITING  
Monitoring and auditing will be standardized and performed in accordance with GSK’s or 
delegated contract research organization’s (CRO) standard operating procedures and 
applicable regulatory requirements (e.g., FDA, EMA, and ICH guidelines).  
Prior to enrolment of the first study subject, GSK or delegate will train investigators and/or 
their study staff on the study protocol, all applicable study procedures, documentation 
practices and all electronic systems. CRFs supplied by the Sponsor must be completed for 
each enrolled subject (see section 8.3.1, All Enrolled Set for definition of enrolled subject). 
For subjects not enrolled, information will be stored in source documents only. 
Documentation of screened but not enrolled subjects must be maintained at the site and 
made available for review by the site monitor. Data and documents will be checked by the 
Sponsor and/or monitor.  
9.1  
Source Documentation  
Prior to the start of the study, the site staff participating in the study conduct will be 
instructed on what documents will be required for review as source documents. The kinds 
of documents that will serve as source documents will be agreed between Sponsor or 
delegate and investigator and designees and specified in the SDAF prior to subject 
enrolment.  
In addition, source documentation must include all of the following: subject identification 
(on each page), eligibility and participation, proper informed consent procedures, dates of 
visits, adherence to protocol procedures, adequate reporting and follow-up of adverse 

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events, documentation of prior/concomitant medication/vaccines, study vaccine 
receipt/dispensing/return records, study vaccine administration information, any data 
collected by a telephone conversation with the subject and date of completion and reason.  
The subject must also allow access to the subject’s medical records. Each subject must be 
informed of this prior to the start of the study and consent for access to medical records 
may be required in accordance with local regulations.  
All safety data reported by subjects must be written down in source documents prior to 
entry of the data into CRFs. If there are multiple sources of information (e.g., Subject Diary, 
verbal report of the subject, telephone contact details, medical chart) supporting the 
diagnosis of an adverse event, these sources must be identified in the source documents, 
discrepancies between sources clarified, the ultimate diagnosis must be justified and written 
in the source documents, and this diagnosis must be captured in the Adverse Event CRF 
(AE CRF).   
9.2  
Study Monitoring, Auditing and Source Data Verification  
Prior to enrolment of the first study subject, the Sponsor or its designee (e.g., a CRO) will 
develop a Clinical Monitoring Plan to specify how centralized and/or on-site monitoring, 
including clinical specimens reconciliation, will be performed for the study. Study progress 
will be monitored by the Sponsor or its designee as frequently as necessary to ensure:  
• 
That the rights and well-being of human subjects are protected,  
• 
The reported study data are accurate, complete, and verifiable from the source 
documents and  
• 
The conduct of the study is in compliance with the current approved 
protocol/amendment(s), GCP and applicable regulatory requirements.  
Contact details for the Sponsor team or its designee involved in study monitoring will be 
provided to the investigator. Study data recorded on CRFs will be verified by checking the 
CRF entries against source documents in order to ensure data completeness and accuracy 
as required by study protocol except for those parameters which are specifically described 
in section 7, Assessment being entered directly into the EDC system.  
Data verification may also be performed through a centralized review of data (e.g., checking 
for outliers or other anomalies). Additional documents such as the investigator site file, 
pharmacy records, and informed consent documentation must also be available for review 
if requested. Arrangements for monitoring visits will be made in advance in accordance 
with the monitoring plan, except in case of emergency.  
The investigator and/or site staff must make source documents of subjects enrolled in this 
study available for inspection by GSK Bio or its representative at the time of each 
monitoring visit and Sponsor audits, when applicable. These documents must also be 
available for inspection, verification and copying, as required by regulations, by officials 

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of the regulatory health authorities (e.g., FDA, EMA and others) and/or ECs/IRBs. The 
investigator and study site staff must comply with applicable privacy, data protection and 
medical confidentiality laws for use and disclosure of information related to the study and 
enrolled subjects.  
10. 
DATA MANAGEMENT  
10.1 
Data Entry and Management  
In this study, all clinical data (including, but not limited to, AE/SAEs, concomitant 
medications, medical history, and physical assessments), safety data will be entered onto 
case report forms (CRFs) in a timely fashion by the investigator and/or the investigator’s 
dedicated site staff. Data entered onto CRFs are stored on a secure website. The data 
collected on this secure website are assimilated into an electronic data capture (EDC) 
system, which is compliant with Title 21 Part 11 policies of the Code of Federal Regulations 
(FDA 1997). The data system includes password protection and internal quality checks. 
The EDC system will be designed and validated by the Sponsor prior to activation for data 
entry by sites. The investigator or designated delegate must review data entered and 
electronically sign the CRFs to verify their accuracy.  
Access to the EDC system for data entry or review will require training and distinct 
individual access code assignments to those site staff members who will be entering study 
data and those involved in study oversight who may review study data. Data are collected 
within the EDC system, to which the Sponsor and site monitors have exclusively “read 
only” access.  
10.2 
Data Clarification  
As part of the conduct of the trial, the Sponsor may have questions about the data entered 
by the site, referred to as queries. The monitors, the Sponsor and delegated DM are the only 
parties that can generate a query. All corrections and clarifications will be entered into the 
EDC system and will be identified by the person entering the information, the reason for 
the change, as well as the time of the changes made. If changes are made to a previously 
and electronically signed CRF, the investigator must confirm and endorse the changes.  
10.3 
Data Protection  
The Sponsor respect the subjects’ rights to privacy and will ensure the confidentiality of 
their medical information in accordance with all applicable laws and regulations.  
The Sponsor as Data Controller according to the European Directive on the protection of 
individuals with regard to the processing of personal data and on the free movement of such 
data (95/46/EC) confirms herewith compliance to Directive 95/46/EC in all stages of Data 
Management.  
11. 
RECORD RETENTION  

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Following closure of the study, the investigator must maintain all site study records (except 
for those required by local regulations to be maintained elsewhere) in a safe and secure 
location. The records must be easily accessible, when needed (e.g. audit or inspection), and 
must be available for review in conjunction with assessment of the facility, supporting 
systems, and staff. Where permitted by applicable laws/regulations or institutional policy, 
some or all of these records can be maintained in a validated format other than hard copy 
(e.g. microfiche, scanned, electronic); however, caution needs to be exercised before such 
action is taken. The investigator must ensure that all reproductions are legible and are a true 
and accurate copy of the original and meet accessibility and retrieval standards, including 
re-generating a hard copy, if required. Furthermore, the investigator must ensure that an 
acceptable back-up of the reproductions exists and that there is an acceptable quality control 
procedure in place for making these reproductions.  
The Sponsor will inform the investigator/institution of the time period for retaining these 
records to comply with all applicable regulatory requirements. The minimum retention time 
will meet the strictest standard applicable to a particular site, as dictated by ICH GCP, any 
institutional requirements, applicable laws or regulations, or GSK standards/procedures, 
otherwise, the minimum retention period will default to 25 years after completion of the 
study report.  
The investigator/institution must notify the Sponsor of any changes in the archival 
arrangements, including, but not limited to archival at an off-site facility, transfer of 
ownership of the records in the event the investigator leaves the site. The principles for the 
storage of laboratory samples are provided below:  
Collected samples will be stored for a maximum of 20 years (counting from when the last 
subject performed the last study visit), unless local rules, regulations or guidelines require 
different timeframes or different procedures, which will then be in line with the subject 
consent. These extra requirements need to be communicated formally to and discussed and 
agreed with the Sponsor.  
12. 
USE OF INFORMATION AND PUBLICATION  
GSK assures that key results of this clinical study will be posted in a publicly accessible 
database within the required time-frame from the end of study as defined in section 3.9, 
End of Study.  
In accordance with standard editorial, ethical practices and current guidelines of Good 
Publication Practice (Graf 2009), GSK will generally support publication of multicenter 
studies only in their entirety and not as individual center data. In this case, a coordinating 
investigator will be designated by mutual agreement prior to the start of the study. The 
coordinating investigator will also sign the clinical study report on behalf of the principal 
investigators (CPMP/EWP/2747/00). Authorship will be determined by mutual agreement 
and in line with International Committee of Medical Journal Editors authorship 

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requirements. Any formal publication of the study in which contribution of GSK personnel 
exceeded that of conventional monitoring will be considered as a joint publication by the 
investigator and the appropriate GSK personnel.  
The Sponsor must be notified of any intent to publish data collected from the study and 
prior approval from the Sponsor must be obtained prior to submission for publication.  

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13. 
ETHICAL CONSIDERATIONS  
13.1  Regulatory and Ethical Compliance  
The study will be conducted in compliance with the protocol, GCP and applicable 
regulatory requirement(s).  
This clinical study was designed and shall be implemented and reported in accordance with 
the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local 
regulations including European Directive 2001/20/EC, GSK codes on protection of human 
rights, and with the ethical principles laid down in the Declaration of Helsinki (European 
Council 2001, US Code of Federal Regulations, ICH 1997).  
The Sponsor will have an account for the trial in the French national database (VRB – 
Volontaires pour la Recherche Biomédicale) where investigator will register each volunteer 
at the day of enrollment.  
After the end of the study, each subject will receive a monetary compensation for a total of 
530 euros to cover for the time spent and any inconvenience due to the study participation. 
This indemnification will be proportional to the number of visits completed as follows:  
- 
50 euros: screening visit  
- 
120 euros: vaccination visit   
- 
90 euros: follow up visit  
13.2 
Informed Consent Procedures  
Eligible subjects may only be included in the study after providing written informed 
consent, as described in section 5.1.1, Informed Consent/Assent. Before the start of the 
study, the investigator will have the informed consent and any other materials that will be 
provided to the subjects reviewed and approved by the IRB/EC. This review and approval 
will be documented and stored with other study documents. The investigator or designee 
must fully inform the subject of all pertinent aspects of the study. A copy of the written 
informed consent will be given to the subject. The subject must be allowed ample time to 
ask about the details of the study and to make a decision as to whether or not to participate 
in the study. The subject must sign the consent form indicating their agreement to 
participate in the study before any study-related procedures are conducted. The informed 
consent process may be conducted up to 21 days prior to vaccination on day 1. If the subject 
is unable to read and write, a witness must be present during the informed consent 
discussion and at the time of informed consent signature.  
Prior to the start of the study, the Sponsor will provide to investigators a proposed informed 
consent form that complies with the ICH GCP guideline and regulatory requirements and 
is considered appropriate for this study. Any changes to the proposed consent form 

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suggested by the investigator must be agreed to by the Sponsor before submission to the 
IRB/EC and a copy of the approved version must be provided to the Sponsor monitor after 
IRB/EC approval.  
Women of childbearing potential should be informed that taking the study medication may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree 
that in order to participate in the study they must adhere to the contraception requirements 
indicated in the protocol for the duration of the study. If case of doubts on the ability of a 
subject to adhere to these requirements, that subject should not be allowed in the study  
13.3 
Responsibilities of the Investigator and IRB/EC  
The protocol and the proposed informed consent form must be reviewed and approved by 
a properly constituted IRB/EC before study start. Properly constituted IRB/EC is defined 
in ICH Guideline for Good Clinical Practice E6 (R1), Section 3 (ICH 1997). A signed and 
dated statement that the protocol and informed consent have been approved by the IRB/EC 
must be given to GSK before study initiation. Prior to study start and at any time the 
protocol is amended during study conduct, the investigator is required to sign a protocol 
signature page confirming his/her agreement to conduct the study in accordance with these 
documents and all of the instructions and procedures found in this protocol and to give 
access to all relevant data and records to GSK monitors, auditors, GSK Clinical Quality 
Assurance representatives, designated agents of GSK, IRBs/ECs, and regulatory authorities 
as required. If an inspection of the clinical site is requested by a regulatory authority, the 
investigator must inform GSK immediately that this request has been made. The 
investigator also responsible for the following:  
• 
Maintaining a list of appropriately qualified persons to whom the investigator has 
delegated significant study-related duties  
• 
Demonstrating the capability of recruiting the required number of suitable subjects 
within the recruitment period  
• 
Demonstrating sufficient time and staffing to properly conduct and complete the study 
within the agreed study period  
• 
Ensuring that all persons assisting with the study are adequately informed about the 
protocol, the investigational product(s), and their study-related duties and functions  
• 
Ensuring that appropriately trained health care professionals are responsible for all 
study-related medical decisions and for ensuring appropriate medical care of subjects 
experiencing any adverse event related to the study  
• 
If permission to do so is given by the subject, ensuring that the subject’s primary 
healthcare provider is informed of the subject’s participation in the study.  
The investigator should not implement any deviation from, or changes of the protocol 
without agreement by the Sponsor and prior review and documented approval/favourable 

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opinion from the IRB/IEC of an amendment, except where necessary to eliminate an 
immediate hazard(s) to study subjects, or when the change(s) involves only logistical or 
administrative aspects of the study (e.g., change in monitor(s), change of telephone 
number(s)). In addition, the investigator, or person designated by the investigator, should 
document and explain any deviation from the approved protocol.  
The investigator may implement a deviation from, or a change of, the protocol to eliminate 
an immediate hazard(s) to study subjects without prior IRB/IEC approval/favourable 
opinion. As soon as possible, the implemented deviation or change, the reasons for it, and, 
if appropriate, the proposed protocol amendment(s) should be submitted:  
(a) To the IRB/IEC for review and approval/favourable opinion,  
(b) To GSK for agreement and, if required, (c) To the regulatory 
authority(ies).  
13.4  Protocol Amendments  
An amendment is a written description of change(s) to or formal clarification of a study 
protocol which may impact on the conduct of the clinical study, potential benefit of the 
clinical study, or may affect subject safety, including changes of study objectives, study 
design, subject population, sample sizes, study procedures, or significant administrative 
aspects. An administrative change of a study protocol is a minor correction or clarification 
that has no significant impact on the way the clinical study is to be conducted and no effect 
on subject safety (e.g., change of telephone number(s), logistical changes). Protocol 
amendments must be approved by the Sponsor, health authorities where required, and the 
IRB/EC. In cases when the amendment is required in order to protect the subject safety, the 
amendment can be implemented prior to IRB/EC approval. Notwithstanding, the need for 
formal approval of a protocol amendment, the investigator is expected to take any 
immediate action required for the safety of any subject included in this study, even if this 
action represents a deviation from the protocol. In such cases, the Sponsor should be 
notified of this action, the IRB/EC at the study site, and, if required by local regulations, 
the relevant health authority) should be informed within 10 working days.  
  
14.  
REFERENCE LIST  
Berlanda Scorza, F., Colucci, A. M., Maggiore, L., Sanzone, S., Rossi, O., Ferlenghi, I., 
Pesce, I., Caboni, M., Norais, N., Di Cioccio, V., Saul, A. & Gerke, C. 2012. High Yield 
Production Process For Shigella Outer Membrane Particles. Plos One, 7, E35616.  
Code of Federal Regulations (1997): Food and Drug Administration, U.S. Department of 
Health and Human Services: Title 21, Part 11: Electronic Records Electronic Signatures. 
Federal Register 62: 13464  

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Cohen, D., Block, C., Green, M. S., Lowell, G. & Ofek, I. 1989. Immunoglobulin M, A, 
And G Antibody Response To Lipopolysaccharide O Antigen In Symptomatic And 
Asymptomatic Shigella Infections. J Clin Microbiol, 27, 162-7.  
Committee for proprietary medicinal products (CPMP), European Agency for the 
Evaluation of Medicinal Products. (1998) Points to consider on clinical investigation of 
medicinal products used in the treatment of osteoarthritis. London, UK.  
Committee for proprietary medicinal products (CPMP), European Agency for the 
Evaluation of Medicinal Products. (2001) Note for guidance on coordinating investigator 
signature of clinical study reports. London, UK.US Department of Health and Human 
Services, Public Health Service, Food and Drug Administration (1992) Guideline for the 
clinical evaluation of analgesic vaccines. Docket No 91D-0425. Rockville, Md.  
European Parliament (1995): Directive 95/46/EC of the European Parliament and of the 
Council of 4 April 2001. Official Journal of the European Communities. L 281/31-39  
European Parliament (2001): Directive 2001/20/EC of the European Parliament and of the 
Council of 4 April 2001. Official Journal of the European Communities. L 121/34-44  
Graf C, Battisti WP, Bridges D (2009). Good publication practice for communicating 
company Sponsored medical research: the GPP2 guidelines. BMJ; 339: b4330  
Kotloff, K. L., Winickoff, J. P., Ivanoff, B., Clemens, J. D., Swerdlow, D. L., Sansonetti, P. J., 
Adak, G. K. & Levine, M. M. (1999). Global Burden Of Shigella Infections: Implications For 
Vaccine Development And Implementation Of Control Strategies. Bull World Health Organ, 
77, 651-66.  
ICH (1997) ICH Harmonised Tripartite ICH Guideline for Good Clinical Practices E6 (R1). 
Federal Register, 62 (90): 25691-25709  
ICH (1998) ICH Harmonised Tripartite ICH Guideline for Statistical Principles for Clinical 
Trials E9. Federal Register, 63 (179): 49583  
Livio, S., Strockbine, N. A., Panchalingam, S. (2014). Shigella Isolates From The Global 
Enteric Multicenter Study Inform Vaccine Development. Clin Infect Dis, 59, 933-41.  
U.S. Department of Health and Human Services, Food and Drug Administration, CBER 
(2009): Guidance for Industry Patient-Reported Outcome Measures: Use in Medical 
Product Development to Support Labeling Claims  
US Department of Health and Human Services, Food and Drug Administration (2007) 
Guidance for Industry: toxicity grading scale for healthy adult and adolescent volunteers 
enrolled in preventive vaccine clinical. Rockville, US.  

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59th World Medical Association General Assembly (October 2008) Declaration of Helsinki 
- Ethical Principles for Medical Research Involving Human Subjects. Seoul, Korea  
  
  
  
  
  
  
 

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Appendix 1: Investigator Agreement  
I agree:  
• 
To conduct the study in compliance with this protocol, any future protocol amendments 
or protocol administrative changes, with the terms of the clinical trial agreement and 
with any other study conduct procedures and/or study conduct documents provided by 
GSK.  
• 
To assume responsibility for the proper conduct of the study at this site.  
• 
That I am aware of, and will comply with, ‘Good Clinical Practice’ (GCP) and all 
applicable regulatory requirements.   
• 
To ensure that all persons assisting me with the study are adequately informed about 
the GSK study vaccine(s)/product(s) and other study-related duties and functions as 
described in the protocol.  
• 
To acquire the reference ranges for laboratory tests performed locally and, if required 
by local regulations, obtain the laboratory’s current certification or Quality Assurance 
procedure manual.  
• 
To ensure that no clinical samples (including serum samples) are retained onsite or 
elsewhere without the approval of GSK and the express written informed consent of 
the subject and/or the subject’s legally acceptable representative.   
• 
To perform no other biological assays on the clinical samples except those described 
in the protocol or its amendment(s).   
• 
To co-operate with a representative of GSK in the monitoring process of the study and 
in resolution of queries about the data.  
• 
That I have been informed that certain regulatory authorities require the sponsor to 
obtain and supply, as necessary, details about the investigator’s ownership interest in 
the sponsor or the investigational vaccine(s)/product(s), and more generally about 
his/her financial ties with the sponsor. GSK Biologicals will use and disclose the 
information solely for the purpose of complying with regulatory requirements.  
Hence I:  
• 
Agree to supply GSK with any necessary information regarding ownership interest and 
financial ties (including those of my spouse and dependent children).  
• 
Agree to promptly update this information if any relevant changes occur during the 
course of the study and for one year following completion of the study.   
• 
Agree that GSK Biologicals may disclose any information it has about such ownership 
interests and financial ties to regulatory authorities.  

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• 
Agree to provide GSK with an updated Curriculum Vitae and other documents required 
by regulatory agencies for this study.  

 
 
 
PPD 
PPD 
PPD 

 
 
PPD