Safety Study of Herpes Simplex Vaccine in HSV Seronegative and Seropositive Females Between 10 and 17 Years Old

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

Time frame: From Month 0 to Month 12

Population: The analyses were performed on the Total Vaccinated cohort, which included all subjects who received at least one dose of the study vaccine and for whom data were available.

Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EU/mL). The subset of subjects used for this analysis was 50% of the pre-defined subset of subjects that underwent assessment of biochemical and hematological parameters.

Time frame: At months 0, 7 and 12

Population: The analyses were performed on the According-To-Protocol cohort for immunogenicity, which included all evaluable subjects included in the immunogenicity subset for whom data concerning immunogenicity outcome measures were available (for whom assay results were available for antibodies against the study vaccine antigen component after Vaccination).

Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EU/mL). Analysis was based on an immunogenicity subset, stratified by initial serostatus: HSV seronegative (-)/ seropositive (+), this included gD2-AS04 vaccine recipients, as follows: HSV 1 and HSV 2 seronegative (HSV1-/2-) and HSV 1 seropositive and HSV 2 seronegative (HSV1+/2-)

Time frame: At months 0, 7 and 12

Population: The analysis was performed on the ATP cohort for immunogenicity, in a predefined immunogenicity subset of HSV vaccine recipients (gD2-AS04 Group) who underwent assessment of biochemical and hematological parameters. Data from participants in the Havrix Group and Saline Group were not collected.

Assessed parameters were alanine aminotransferase (ALT), creatinine (CREA), haematocrit (Hct), platelets (PLA), red blood cells (RBC), urea and white blood cells (WBC). A subset of subjects was formed for these analyses. Subjects were categorized according to their results at pre-vaccination at Month 0 (PRE) which were normal, above normal or below the normal range. Per parameter and range, it was assessed whether laboratory values of the subjects were normal, above normal or below the normal range at other timepoints. This outcome presents WBC results.

Time frame: At months 7 and 12

Population: The analyses were performed on a subset of subjects from the Total Vaccinated cohort, which included subjects who received at least one dose of the study vaccine and for whom data were available.

Assessed parameters were alanine aminotransferase (ALT), creatinine (CREA), haematocrit (Hct), platelets (PLA), red blood cells (RBC), urea and white blood cells (WBC). A subset of subjects was formed for these analyses. Subjects were categorized according to their results at pre-vaccination at Month 0 (PRE) which were normal, above normal or below the normal range. Per parameter and range, it was assessed whether laboratory values of the subjects were normal, above normal or below the normal range at other timepoints. This outcome presents UREA results.

Time frame: At months 7 and 12

Population: The analyses were performed on a subset of subjects from the Total Vaccinated cohort, which included subjects who received at least one dose of the study vaccine and for whom data were available.

Assessed parameters were alanine aminotransferase (ALT), creatinine (CREA), haematocrit (Hct), platelets (PLA), red blood cells (RBC), urea and white blood cells (WBC). A subset of subjects was formed for these analyses. Subjects were categorized according to their results at pre-vaccination at Month 0 (PRE) which were normal, above normal or below the normal range. Per parameter and range, it was assessed whether laboratory values of the subjects were normal, above normal or below the normal range at other timepoints. This outcome presents RBC results.

Time frame: At months 7 and 12

Population: The analyses were performed on a subset of subjects from the Total Vaccinated cohort, which included subjects who received at least one dose of the study vaccine and for whom data were available.

Assessed parameters were alanine aminotransferase (ALT), creatinine (CREA), haematocrit (Hct), platelets (PLA), red blood cells (RBC), urea and white blood cells (WBC). A subset of subjects was formed for these analyses. Subjects were categorized according to their results at pre-vaccination at Month 0 (PRE) which were normal, above normal or below the normal range. Per parameter and range, it was assessed whether laboratory values of the subjects were normal, above normal or below the normal range at other timepoints. This outcome presents ALT results.

Time frame: At months 7 and 12

Population: The analyses were performed on a subset of subjects from the Total Vaccinated cohort, which included subjects who received at least one dose of the study vaccine and for whom data were available.

Assessed parameters were alanine aminotransferase (ALT), creatinine (CREA), haematocrit (Hct), platelets (PLA), red blood cells (RBC), urea and white blood cells (WBC). A subset of subjects was formed for these analyses. Subjects were categorized according to their results at pre-vaccination at Month 0 (PRE) which were normal, above normal or below the normal range. Per parameter and range, it was assessed whether laboratory values of the subjects were normal, above normal or below the normal range at other timepoints. This outcome presents CREA results.

Time frame: At months 7 and 12

Population: The analyses were performed on a subset of subjects from the Total Vaccinated cohort, which included subjects who received at least one dose of the study vaccine and for whom data were available.

Assessed parameters were alanine aminotransferase (ALT), creatinine (CREA), haematocrit (Hct), platelets (PLA), red blood cells (RBC), urea and white blood cells (WBC). A subset of subjects was formed for these analyses. Subjects were categorized according to their results at pre-vaccination at Month 0 (PRE) which were normal, above normal or below the normal range. Per parameter and range, it was assessed whether laboratory values of the subjects were normal, above normal or below the normal range at other timepoints. This outcome presents PLA results.

Time frame: At months 7 and 12

Population: The analyses were performed on a subset of subjects from the Total Vaccinated cohort, which included subjects who received at least one dose of the study vaccine and for whom data were available.

Assessed parameters were alanine aminotransferase (ALT), creatinine (CREA), haematocrit (Hct), platelets (PLA), red blood cells (RBC), urea and white blood cells (WBC). A subset of subjects was formed for these analyses. Subjects were categorized according to their results at pre-vaccination at Month 0 (PRE) which were normal, above normal or below the normal range. Per parameter and range, it was assessed whether laboratory values of the subjects were normal, above normal or below the normal range at other timepoints. This outcome presents Hct results.

Time frame: At months 7 and 12

Population: The analyses were performed on a subset of subjects from the Total Vaccinated cohort, which included subjects who received at least one dose of the study vaccine and for whom data were available.

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activities. Grade 3 redness/swelling = greater than (\>) 30mm diameter and persisting more than 24 hours.

Time frame: Within 7 days (Days 0-6) after each and any vaccination

Population: The analyses were performed on the Total Vaccinated cohort, only on subjects with their symptom sheets completed, who received at least one dose of the study vaccine and for whom data were available.

Assessed solicited general symptoms were arthralgia, fatigue, headache, malaise, rash, temperature \[defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)\] and urticaria. Any = occurrence of any general symptom regardless of intensity grade or relation to vaccination. Grade 3 arthralgia, fatigue, headache, malaise, rash = general symptom that prevented normal activity. Grade 3 temperature = greater than 39 degrees Celsius (°C). Grade 3 urticaria = urticaria distributed on at least 4 body areas. Related = general symptom assessed by the investigator as causally related to the study vaccination.

Time frame: Within 7 days (Days 0-6) after each and any vaccination

Population: The analyses were performed on the Total Vaccinated cohort, only on subjects with their symptom sheets completed, who received at least one dose of the study vaccine and for whom data were available.

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 = event which prevented normal, everyday activities. In adults/ adolescents, such an AE would, for example, prevent attendance at work/ school and would necessitate the administration of corrective therapy. Related = event assessed by the investigator as causally related to study vaccination.

Time frame: Within 30 days (Day 0-29) after any vaccination

Population: The analyses were performed on the Total Vaccinated cohort, which included all subjects who received at least one dose of the study vaccine and for whom data were available.

MSCs include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury. For outcomes covering the ESFU period, the Havrix Group and Saline Group were pooled.

Time frame: During the Extended Safety Follow Up (ESFU) period (Month 12 to Month 18)

Population: The analyses were performed on the Total Vaccinated cohort, which included all subjects who received at least one dose of the study vaccine and for whom data were available. For the purpose of this analysis, the subjects from Havrix Group and Saline group were pooled into one group: Pooled Group.

NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. For outcomes covering the ESFU period, the Havrix Group and Saline Group were pooled.

Time frame: During the Extended Safety Follow Up (ESFU) period (Month 12 to Month 18)

Population: The analyses were performed on the Total Vaccinated cohort, which included all subjects who received at least one dose of the study vaccine and for whom data were available. For the purpose of this analysis, the subjects from Havrix Group and Saline group were pooled into one group: Pooled Group.

NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.

Time frame: During the active phase (up to Month 12)

Population: The analyses were performed on the Total Vaccinated cohort, which included all subjects who received at least one dose of the study vaccine and for whom data were available.

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. For outcomes covering the ESFU period, the Havrix Group and Saline Group were pooled.

Time frame: Up to month 18 (during active phase and ESFU period)

Population: The analyses were performed on the Total Vaccinated cohort, which included all subjects who received at least one dose of the study vaccine and for whom data were available. For the purpose of this analysis, the subjects from Havrix Group and Saline group were pooled into one group: Pooled Group.

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. A medically attended visit is an event which prompted the subject to seek medical advice.

Time frame: Within the 30 Day (Day 0-29) post-vaccination period

Population: The analyses were performed on the Total Vaccinated cohort, which included all subjects who received at least one dose of the study vaccine and for whom data were available.

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. A medically attended visit is an event which prompted the subject to seek medical advice.

Time frame: Starting from Day 30 until the end of study (Month 18)

Population: The analyses were performed on the Total Vaccinated cohort, which included all subjects who received at least one dose of the study vaccine and for whom data were available.