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

Study Overview
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Brief Summary
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Main goal of this study is to compare the occurrence of serious adverse events (SAEs) between the herpes simplex (gD2-AS04) vaccine group and the Saline control group throughout the study period (up to month 12). The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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Three groups of females (3000, 1500 and 1500 subjects, respectively) were injected 3 times (at months 0, 1 and 6) with the herpes simplex vaccine, the HavrixTM vaccine (control) and a Saline solution (placebo), respectively. Subjects were followed over 18 months.

Official Title
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A Study to Evaluate the Immunogenicity and Safety of GlaxoSmithKline Biologicals' Herpes Simplex Candidate Vaccine (gD2-AS04) in Healthy HSV Seronegative and Seropositive Female Subjects Aged 10-17 Years.

Conditions
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Herpes Simplex

Intervention / Treatment
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* Biological: GSK208141
* Biological: Havrix (investigational formulation)
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that can and will comply with the requirements of the protocol should be enrolled in the study. Healthy female between, and including, 10 and 17 years of age at the time of the first vaccination. Written informed assent obtained from the subject and written informed consent obtained from a parent or legal guardian of the subject prior to enrolment. If the subject is above the legal age of consent in her country, written informed consent will only be obtained from the subject. Subjects must have a negative urine pregnancy test. Subjects of childbearing potential at the time of study entry must be abstinent or must be using an effective method of birth control for 30 days prior to vaccination and must agree to continue such precautions for two months after completion of the vaccination series. Subjects who reach menarche during the study and therefore are of childbearing potential must agree to follow the same precautions. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. Pregnant or lactating female. Female planning to become pregnant or likely to become pregnant during the first eight months of the study (months 0-8). Any previous confirmed history of, or current clinical signs or symptoms of, oro labial herpes (cold sores), herpetic whitlow or genital herpes disease, such as swelling, papules, vesicles, pustules, ulcers, crusts, fissures, erythema, discharge, dysuria or pain, burning, itching, tingling in the ano-genital area. History of previous or planned vaccination against hepatitis A or a history of hepatitis A infection. Previous vaccination against herpes. History of herpetic keratitis. History of multiform erythema. Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after the first dose of study vaccine with the following exceptions: administration of routine meningococcal, hepatitis B, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccine up to 8 days before and 30 days after the first dose of study vaccine. History of allergic disease or reactions likely to be exacerbated by any component of the study vaccines Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination History of a current acute or chronic autoimmune disease. History of any neurological disorders or seizures, with the exception of a single febrile seizure during childhood. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality Acute disease at the time of enrolment Oral temperature >= 37.5°C (99.5°F) / axillary temperature >= 37.5°C (99.5°F) at the time of enrolment. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GD2-AS04 GROUP<br>Female subjects aged 10-17 years, who received 3 doses of gD2-AS04 vaccine, which were administered intramuscularly in the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule. | Biological: GSK208141<br>* 3 intramuscular doses<br>* Other names: gD2-AS04 vaccine;|
| Active Comparator: HAVRIX GROUP<br>Female subjects aged 10-17 years, who received 3 doses of Havrix, which were administered intramuscularly in the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule. | Biological: Havrix (investigational formulation)<br>* 3 intramuscular doses<br>|
| Placebo Comparator: SALINE GROUP<br>Female subjects aged 10-17 years, who received 3 doses of a saline solution, which were administered intramuscularly in the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule. | Biological: Placebo<br>* 3 intramuscular doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Serious Adverse Events (SAEs) | 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. | From Month 0 to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | 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. | Within 7 days (Days 0-6) after each and any vaccination | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | 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. | Within 7 days (Days 0-6) after each and any vaccination | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | 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. | Within 30 days (Day 0-29) after any vaccination | 
| Number of Subjects With Unsolicited Adverse Events (AEs) With Medically Attended Visits | 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. | Within the 30 Day (Day 0-29) post-vaccination period | 
| Number of Subjects With New Onset Chronic Diseases (NOCD) | NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. | During the active phase (up to Month 12) | 
| Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed | 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. | At months 7 and 12 | 
| Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed | 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. | At months 7 and 12 | 
| Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed | 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. | At months 7 and 12 | 
| Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed | 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. | At months 7 and 12 | 
| Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed | 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. | At months 7 and 12 | 
| Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed | 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. | At months 7 and 12 | 
| Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed | 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. | At months 7 and 12 | 
| Number of Subjects With Unsolicited Adverse Events (AEs) With Medically Attended Visits | 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. | Starting from Day 30 until the end of study (Month 18) | 
| Number of Subjects With Medically Significant Conditions (MSC) | 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. | During the Extended Safety Follow Up (ESFU) period (Month 12 to Month 18) | 
| Number of Subjects With New Onset Chronic Diseases (NOCD) | NOCDs include autoimmune disorders, asthma, type I diabetes, allergies. For outcomes covering the ESFU period, the Havrix Group and Saline Group were pooled. | During the Extended Safety Follow Up (ESFU) period (Month 12 to Month 18) | 
| Number of Subjects With Serious Adverse Events (SAEs) | 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. | Up to month 18 (during active phase and ESFU period) | 
| Anti-glycoprotein D (Anti-gD) Antibody Concentrations | 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-) | At months 0, 7 and 12 | 
| Anti-deacylated Monophosphoryl Lipid A (Anti-MPL) Antibody Concentrations | 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. | At months 0, 7 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adolescents, Herpes Simplex vaccine, Safety, Immunogenicity