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

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.

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.

Study Overview

• Status: Completed
• Conditions: Herpes Simplex
• Intervention / Treatment: Biological: GSK208141; Biological: Havrix (investigational formulation); Biological: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5960
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2606
      • GSK Investigational Site
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • GSK Investigational Site
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • GSK Investigational Site
  • Tasmania
    • Hobart, Tasmania, Australia
      • GSK Investigational Site
  • Victoria
    • Carlton, Victoria, Australia, 3053
      • GSK Investigational Site
• Belgium
  • Gent, Belgium, 9000
    • GSK Investigational Site
  • Wilrijk, Belgium, 2610
    • GSK Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2C8
      • GSK Investigational Site
  • British Columbia
    • Surrey, British Columbia, Canada, V3R 8P8
      • GSK Investigational Site
    • Vancouver, British Columbia, Canada, V6H 3N1
      • GSK Investigational Site
  • Ontario
    • Ottawa, Ontario, Canada, K1S 0G8
      • GSK Investigational Site
  • Quebec
    • Beauport, Quebec, Canada, G1E 7G9
      • GSK Investigational Site
    • Sainte-Foy, Quebec, Canada, G1V 4G2
      • GSK Investigational Site
• Denmark
  • Aarhus N, Denmark, 8200
    • GSK Investigational Site
• Estonia
  • Tallinn, Estonia, 10617
    • GSK Investigational Site
  • Tartu, Estonia, 50417
    • GSK Investigational Site
• France
  • Château Renault, France, 37110
    • GSK Investigational Site
  • Derval, France, 44590
    • GSK Investigational Site
  • Evreux, France, 27000
    • GSK Investigational Site
  • Haute Goulaine, France, 44115
    • GSK Investigational Site
  • La Chapelle sur Erdre, France, 44240
    • GSK Investigational Site
  • Le Temple De Bretagne, France, 44360
    • GSK Investigational Site
  • Luynes, France, 37230
    • GSK Investigational Site
  • Nantes, France, 44300
    • GSK Investigational Site
  • Nantes, France, 44000
    • GSK Investigational Site
  • Nort sur Erdre, France, 44390
    • GSK Investigational Site
  • Paris, France, 75015
    • GSK Investigational Site
  • Pont de L'Arche, France, 27340
    • GSK Investigational Site
  • Saint Aubin des Chateaux, France, 44110
    • GSK Investigational Site
  • Saint Avertin, France, 37550
    • GSK Investigational Site
  • Saint Sebastien sur Loire, France, 44230
    • GSK Investigational Site
  • Tours, France, 37000
    • GSK Investigational Site
• Greece
  • Athens, Greece, 11528
    • GSK Investigational Site
  • Athens, Greece, 11527
    • GSK Investigational Site
  • Komotini, Greece, 69100
    • GSK Investigational Site
  • Thessaloniki, Greece, 54636
    • GSK Investigational Site
• Hungary
  • Bordány, Hungary, 6795
    • GSK Investigational Site
  • Budapest, Hungary, 1089
    • GSK Investigational Site
  • Győr, Hungary, 9024
    • GSK Investigational Site
  • Hódmezővásárhely, Hungary, 6800
    • GSK Investigational Site
  • Szeged, Hungary, 6720
    • GSK Investigational Site
  • Szeged, Hungary, 6723
    • GSK Investigational Site
  • Zsombó, Hungary, 6792
    • GSK Investigational Site
• Iceland
  • Gardabaer, Iceland, 210
    • GSK Investigational Site
  • Kopavogur, Iceland
    • GSK Investigational Site
  • Reykjavik, Iceland, 112
    • GSK Investigational Site
• Lithuania
  • Kaunas, Lithuania, LT-47144
    • GSK Investigational Site
  • Panevezys, Lithuania, LT-37355
    • GSK Investigational Site
  • Vilnius, Lithuania, LT-01205
    • GSK Investigational Site
  • Vilnius, Lithuania, LT-02169
    • GSK Investigational Site
  • Vilnius, Lithuania, LT-07156
    • GSK Investigational Site
• Netherlands
  • Rotterdam, Netherlands, 3011 EN
    • GSK Investigational Site
• New Zealand
  • Christchurch, New Zealand, 8001
    • GSK Investigational Site
• Norway
  • Bergen, Norway, N-5021
    • GSK Investigational Site
  • Oslo, Norway, N-0159
    • GSK Investigational Site
• Romania
  • Bucharest, Romania, 077190
    • GSK Investigational Site
  • Bucharest, Romania, 020125
    • GSK Investigational Site
  • Bucharest, Romania
    • GSK Investigational Site
  • Bucuresti, Romania
    • GSK Investigational Site
• Spain
  • Blanes, Spain
    • GSK Investigational Site
  • Castellon, Spain
    • GSK Investigational Site
  • Madrid, Spain, 28009
    • GSK Investigational Site
  • Montgat/Barcelona, Spain, 08390
    • GSK Investigational Site
  • Valencia, Spain, 46017
    • GSK Investigational Site
  • Valencia, Spain, 46024
    • GSK Investigational Site
  • Valencia, Spain, 46023
    • GSK Investigational Site
  • Valencia, Spain, 46021
    • GSK Investigational Site
• Sweden
  • Göteborg, Sweden, SE-416 85
    • GSK Investigational Site
  • Karlskrona, Sweden, SE-371 41
    • GSK Investigational Site
  • Linköping, Sweden, SE-581 85
    • GSK Investigational Site
  • Malmö, Sweden, SE-205 02
    • GSK Investigational Site
  • Umeå, Sweden, SE-901 85
    • GSK Investigational Site
  • Örebro, Sweden, SE-702 11
    • GSK Investigational Site
• United Kingdom
  • Bradford, United Kingdom, BD5 0JD
    • GSK Investigational Site
  • Doncaster, United Kingdom, DN1 2EG
    • GSK Investigational Site
  • Leeds, United Kingdom, LS12 1JE
    • GSK Investigational Site
  • London, United Kingdom, SW10 9TH
    • GSK Investigational Site
  • Sheffield, United Kingdom, S10 2JF
    • GSK Investigational Site
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO14 0YG
      • GSK Investigational Site
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY4 3AD
      • GSK Investigational Site
    • Blackpool, Lancashire, United Kingdom, FY2 9RS
      • GSK Investigational Site
    • Blackpool, Lancashire, United Kingdom, FY3 7DG
      • GSK Investigational Site
    • Bolton, Lancashire, United Kingdom, BL4 9QZ
      • GSK Investigational Site
  • Warwickshire
    • Coventry, Warwickshire, United Kingdom, CV6 4DD
      • GSK Investigational Site
    • Coventry, Warwickshire, United Kingdom, CV5 6EU
      • GSK Investigational Site
  • West Midlands
    • Coventry, West Midlands, United Kingdom, CV2 1AX
      • GSK Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • GSK Investigational Site
    • Birmingham, Alabama, United States, 35233
      • GSK Investigational Site
  • Arizona
    • Chandler, Arizona, United States, 85224
      • GSK Investigational Site
    • Mesa, Arizona, United States, 85213
      • GSK Investigational Site
    • Mesa, Arizona, United States, 85201
      • GSK Investigational Site
    • Tempe, Arizona, United States, 85282
      • GSK Investigational Site
    • Tucson, Arizona, United States, 85710
      • GSK Investigational Site
  • California
    • Beverly Hills, California, United States, 90211
      • GSK Investigational Site
    • Fountain Valley, California, United States, 92708
      • GSK Investigational Site
    • Long Beach, California, United States, 90806
      • GSK Investigational Site
    • Rolling Hills Estates, California, United States, 90274
      • GSK Investigational Site
  • Colorado
    • Centennial, Colorado, United States, 80112
      • GSK Investigational Site
    • Littleton, Colorado, United States, 80234
      • GSK Investigational Site
    • Thornton, Colorado, United States, 80233
      • GSK Investigational Site
    • Westminster, Colorado, United States, 80234
      • GSK Investigational Site
    • Wheat Ridge, Colorado, United States, 80033
      • GSK Investigational Site
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • GSK Investigational Site
  • Florida
    • Clearwater, Florida, United States, 33759
      • GSK Investigational Site
    • Cocoa Beach, Florida, United States, 32931
      • GSK Investigational Site
    • Melbourne, Florida, United States, 332901
      • GSK Investigational Site
    • Naples, Florida, United States, 34102
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60614
      • GSK Investigational Site
  • Kansas
    • Arkansas City, Kansas, United States, 67005
      • GSK Investigational Site
    • Wichita, Kansas, United States, 67207
      • GSK Investigational Site
  • Maryland
    • Towson, Maryland, United States, 21286
      • GSK Investigational Site
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • GSK Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • GSK Investigational Site
    • Saint Louis, Missouri, United States, 63104
      • GSK Investigational Site
  • New Jersey
    • Whitehouse Station, New Jersey, United States, 08889
      • GSK Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • GSK Investigational Site
  • New York
    • Bronx, New York, United States, 10461
      • GSK Investigational Site
    • Bronx, New York, United States, 10467-2490
      • GSK Investigational Site
    • Stony Brook, New York, United States, 11794-8480
      • GSK Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • GSK Investigational Site
    • Sylva, North Carolina, United States, 28779
      • GSK Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • GSK Investigational Site
  • Ohio
    • Akron, Ohio, United States, 44308-1062
      • GSK Investigational Site
    • Cincinnati, Ohio, United States, 45229
      • GSK Investigational Site
    • Cleveland, Ohio, United States, 44121
      • GSK Investigational Site
    • Columbus, Ohio, United States, 43214
      • GSK Investigational Site
    • Columbus, Ohio, United States, 43235
      • GSK Investigational Site
    • Hilliard, Ohio, United States, 43026
      • GSK Investigational Site
    • Pickerington, Ohio, United States, 43147
      • GSK Investigational Site
    • Westerville, Ohio, United States, 43082
      • GSK Investigational Site
  • Oregon
    • Portland, Oregon, United States, 97216
      • GSK Investigational Site
  • Pennsylvania
    • Beaver, Pennsylvania, United States, 15009
      • GSK Investigational Site
    • Erie, Pennsylvania, United States, 16508
      • GSK Investigational Site
    • Erie, Pennsylvania, United States, 16505
      • GSK Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15227
      • GSK Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15241
      • GSK Investigational Site
  • Tennessee
    • Gray, Tennessee, United States, 37615
      • GSK Investigational Site
    • Kingsport, Tennessee, United States, 37660
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78752
      • GSK Investigational Site
    • Beaumont, Texas, United States, 77701
      • GSK Investigational Site
    • Galveston, Texas, United States, 77555-0188
      • GSK Investigational Site
    • Lake Jackson, Texas, United States, 77566
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
    • Temple, Texas, United States, 76508
      • GSK Investigational Site
  • Utah
    • Magna, Utah, United States, 84044
      • GSK Investigational Site
    • Salt Lake City, Utah, United States, 84109
      • GSK Investigational Site
    • Salt Lake City, Utah, United States, 84121
      • GSK Investigational Site
    • Sandy, Utah, United States, 84070
      • GSK Investigational Site
    • West Jordan, Utah, United States, 84088
      • GSK Investigational Site
    • West Jordan, Utah, United States, 84084
      • GSK Investigational Site
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • GSK Investigational Site
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GD2-AS04 GROUP; 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; 3 intramuscular doses; Other Names: Herpes simplex vaccine; gD2-AS04 vaccine
Active Comparator: HAVRIX GROUP; 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); 3 intramuscular doses
Placebo Comparator: SALINE GROUP; 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; 3 intramuscular doses

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Verstraeten T, Descamps D, David MP, Zahaf T, Hardt K, Izurieta P, Dubin G, Breuer T. Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 2008 Dec 2;26(51):6630-8. doi: 10.1016/j.vaccine.2008.09.049.
• Tavares F, Cheuvart B, Heineman T, Arellano F, Dubin G. Meta-analysis of pregnancy outcomes in pooled randomized trials on a prophylactic adjuvanted glycoprotein D subunit herpes simplex virus vaccine. Vaccine. 2013 Mar 25;31(13):1759-64. doi: 10.1016/j.vaccine.2013.01.002. Epub 2013 Jan 10.
• HSV-040 Study Group, Abu-Elyazeed RR, Heineman T, Dubin G, Fourneau M, Leroux-Roels I, Leroux-Roels G, Richardus JH, Ostergaard L, Diez-Domingo J, Poder A, Van Damme P, Romanowski B, Blatter M, Silfverdal SA, Berglund J, Josefsson A, Cunningham AL, Flodmark CE, Tragiannidis A, Dobson S, Olafsson J, Puig-Barbera J, Mendez M, Barton S, Bernstein D, Mares J, Ratner P. Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age: results from a randomised, controlled, double-blind trial. Vaccine. 2013 Dec 9;31(51):6136-43. doi: 10.1016/j.vaccine.2013.06.081. Epub 2013 Jul 9.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2004
• Primary Completion (Actual): July 24, 2007
• Study Completion (Actual): July 24, 2007

Study Registration Dates

• First Submitted: September 21, 2005
• First Submitted That Met QC Criteria: September 21, 2005
• First Posted (Estimate): September 23, 2005

Study Record Updates

• Last Update Posted (Actual): January 7, 2019
• Last Update Submitted That Met QC Criteria: January 3, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Adolescents; Safety; Immunogenicity; Herpes Simplex vaccine
• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; DNA Virus Infections; Skin Diseases, Infectious; Skin Diseases, Viral; Herpesviridae Infections; Herpes Simplex; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 208141/040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Dataset Specification
   Information identifier: 208141/040
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 208141/040
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 208141/040
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 208141/040
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 208141/040
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 208141/040
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register