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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00224484
• Collaborator: (none)
• Enrollment: 5,960
• Locations: 152
• Arms: 3
• Actual Duration (Months): 39.5
• Patients Per Site: 39.2
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Herpes Simplex	Biological: GSK208141; Biological: Havrix (investigational formulation); Biological: Placebo	Phase 3

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 Design

• Study Type: Interventional
• Actual Enrollment: 5960 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: 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.
• Actual Study Start Date: Apr 7, 2004
• Actual Primary Completion Date: Jul 24, 2007
• Actual Study Completion Date: Jul 24, 2007

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Serious Adverse Events (SAEs) [From Month 0 to Month 12]

   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.

Secondary Outcome Measures

1. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [Within 7 days (Days 0-6) after each and any vaccination]

   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.

2. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [Within 7 days (Days 0-6) after each and any vaccination]

   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.

3. Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) [Within 30 days (Day 0-29) after any vaccination]

   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.

4. Number of Subjects With Unsolicited Adverse Events (AEs) With Medically Attended Visits [Within the 30 Day (Day 0-29) post-vaccination period]

   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.

5. Number of Subjects With New Onset Chronic Diseases (NOCD) [During the active phase (up to Month 12)]

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

6. Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed [At months 7 and 12]

   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.

7. Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed [At months 7 and 12]

   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.

8. Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed [At months 7 and 12]

   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.

9. Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed [At months 7 and 12]

   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.

10. Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed [At months 7 and 12]

    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.

11. Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed [At months 7 and 12]

    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.

12. Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed [At months 7 and 12]

    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.

13. Number of Subjects With Unsolicited Adverse Events (AEs) With Medically Attended Visits [Starting from Day 30 until the end of study (Month 18)]

    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.

14. Number of Subjects With Medically Significant Conditions (MSC) [During the Extended Safety Follow Up (ESFU) period (Month 12 to Month 18)]

    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.

15. Number of Subjects With New Onset Chronic Diseases (NOCD) [During the Extended Safety Follow Up (ESFU) period (Month 12 to Month 18)]

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

16. Number of Subjects With Serious Adverse Events (SAEs) [Up to month 18 (during active phase and ESFU period)]

    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.

17. Anti-glycoprotein D (Anti-gD) Antibody Concentrations [At months 0, 7 and 12]

    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-)

18. Anti-deacylated Monophosphoryl Lipid A (Anti-MPL) Antibody Concentrations [At months 0, 7 and 12]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 17 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35209
2	GSK Investigational Site	Birmingham	Alabama	United States	35233
3	GSK Investigational Site	Chandler	Arizona	United States	85224
4	GSK Investigational Site	Mesa	Arizona	United States	85201
5	GSK Investigational Site	Mesa	Arizona	United States	85213
6	GSK Investigational Site	Tempe	Arizona	United States	85282
7	GSK Investigational Site	Tucson	Arizona	United States	85710
8	GSK Investigational Site	Beverly Hills	California	United States	90211
9	GSK Investigational Site	Fountain Valley	California	United States	92708
10	GSK Investigational Site	Long Beach	California	United States	90806
11	GSK Investigational Site	Rolling Hills Estates	California	United States	90274
12	GSK Investigational Site	Centennial	Colorado	United States	80112
13	GSK Investigational Site	Littleton	Colorado	United States	80234
14	GSK Investigational Site	Thornton	Colorado	United States	80233
15	GSK Investigational Site	Westminster	Colorado	United States	80234
16	GSK Investigational Site	Wheat Ridge	Colorado	United States	80033
17	GSK Investigational Site	Norwich	Connecticut	United States	06360
18	GSK Investigational Site	Clearwater	Florida	United States	33759
19	GSK Investigational Site	Cocoa Beach	Florida	United States	32931
20	GSK Investigational Site	Melbourne	Florida	United States	332901
21	GSK Investigational Site	Naples	Florida	United States	34102
22	GSK Investigational Site	Chicago	Illinois	United States	60614
23	GSK Investigational Site	Arkansas City	Kansas	United States	67005
24	GSK Investigational Site	Wichita	Kansas	United States	67207
25	GSK Investigational Site	Towson	Maryland	United States	21286
26	GSK Investigational Site	Fridley	Minnesota	United States	55432
27	GSK Investigational Site	Saint Louis	Missouri	United States	63104
28	GSK Investigational Site	Saint Louis	Missouri	United States	63141
29	GSK Investigational Site	Whitehouse Station	New Jersey	United States	08889
30	GSK Investigational Site	Albuquerque	New Mexico	United States	87102
31	GSK Investigational Site	Bronx	New York	United States	10461
32	GSK Investigational Site	Bronx	New York	United States	10467-2490
33	GSK Investigational Site	Stony Brook	New York	United States	11794-8480
34	GSK Investigational Site	Raleigh	North Carolina	United States	27609
35	GSK Investigational Site	Sylva	North Carolina	United States	28779
36	GSK Investigational Site	Winston-Salem	North Carolina	United States	27103
37	GSK Investigational Site	Akron	Ohio	United States	44308-1062
38	GSK Investigational Site	Cincinnati	Ohio	United States	45229
39	GSK Investigational Site	Cleveland	Ohio	United States	44121
40	GSK Investigational Site	Columbus	Ohio	United States	43214
41	GSK Investigational Site	Columbus	Ohio	United States	43235
42	GSK Investigational Site	Hilliard	Ohio	United States	43026
43	GSK Investigational Site	Pickerington	Ohio	United States	43147
44	GSK Investigational Site	Westerville	Ohio	United States	43082
45	GSK Investigational Site	Portland	Oregon	United States	97216
46	GSK Investigational Site	Beaver	Pennsylvania	United States	15009
47	GSK Investigational Site	Erie	Pennsylvania	United States	16505
48	GSK Investigational Site	Erie	Pennsylvania	United States	16508
49	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15227
50	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15241
51	GSK Investigational Site	Gray	Tennessee	United States	37615
52	GSK Investigational Site	Kingsport	Tennessee	United States	37660
53	GSK Investigational Site	Austin	Texas	United States	78752
54	GSK Investigational Site	Beaumont	Texas	United States	77701
55	GSK Investigational Site	Galveston	Texas	United States	77555-0188
56	GSK Investigational Site	Lake Jackson	Texas	United States	77566
57	GSK Investigational Site	San Antonio	Texas	United States	78229
58	GSK Investigational Site	Temple	Texas	United States	76508
59	GSK Investigational Site	Magna	Utah	United States	84044
60	GSK Investigational Site	Salt Lake City	Utah	United States	84109
61	GSK Investigational Site	Salt Lake City	Utah	United States	84121
62	GSK Investigational Site	Sandy	Utah	United States	84070
63	GSK Investigational Site	West Jordan	Utah	United States	84084
64	GSK Investigational Site	West Jordan	Utah	United States	84088
65	GSK Investigational Site	Norfolk	Virginia	United States	23510
66	GSK Investigational Site	Marshfield	Wisconsin	United States	54449
67	GSK Investigational Site	Garran	Australian Capital Territory	Australia	2606
68	GSK Investigational Site	Westmead	New South Wales	Australia	2145
69	GSK Investigational Site	South Brisbane	Queensland	Australia	4101
70	GSK Investigational Site	Hobart	Tasmania	Australia
71	GSK Investigational Site	Carlton	Victoria	Australia	3053
72	GSK Investigational Site	Gent		Belgium	9000
73	GSK Investigational Site	Wilrijk		Belgium	2610
74	GSK Investigational Site	Edmonton	Alberta	Canada	T6G 2C8
75	GSK Investigational Site	Surrey	British Columbia	Canada	V3R 8P8
76	GSK Investigational Site	Vancouver	British Columbia	Canada	V6H 3N1
77	GSK Investigational Site	Ottawa	Ontario	Canada	K1S 0G8
78	GSK Investigational Site	Beauport	Quebec	Canada	G1E 7G9
79	GSK Investigational Site	Sainte-Foy	Quebec	Canada	G1V 4G2
80	GSK Investigational Site	Aarhus N		Denmark	8200
81	GSK Investigational Site	Tallinn		Estonia	10617
82	GSK Investigational Site	Tartu		Estonia	50417
83	GSK Investigational Site	Château Renault		France	37110
84	GSK Investigational Site	Derval		France	44590
85	GSK Investigational Site	Evreux		France	27000
86	GSK Investigational Site	Haute Goulaine		France	44115
87	GSK Investigational Site	La Chapelle sur Erdre		France	44240
88	GSK Investigational Site	Le Temple De Bretagne		France	44360
89	GSK Investigational Site	Luynes		France	37230
90	GSK Investigational Site	Nantes		France	44000
91	GSK Investigational Site	Nantes		France	44300
92	GSK Investigational Site	Nort sur Erdre		France	44390
93	GSK Investigational Site	Paris		France	75015
94	GSK Investigational Site	Pont de L'Arche		France	27340
95	GSK Investigational Site	Saint Aubin des Chateaux		France	44110
96	GSK Investigational Site	Saint Avertin		France	37550
97	GSK Investigational Site	Saint Sebastien sur Loire		France	44230
98	GSK Investigational Site	Tours		France	37000
99	GSK Investigational Site	Athens		Greece	11527
100	GSK Investigational Site	Athens		Greece	11528
101	GSK Investigational Site	Komotini		Greece	69100
102	GSK Investigational Site	Thessaloniki		Greece	54636
103	GSK Investigational Site	Bordány		Hungary	6795
104	GSK Investigational Site	Budapest		Hungary	1089
105	GSK Investigational Site	Győr		Hungary	9024
106	GSK Investigational Site	Hódmezővásárhely		Hungary	6800
107	GSK Investigational Site	Szeged		Hungary	6720
108	GSK Investigational Site	Szeged		Hungary	6723
109	GSK Investigational Site	Zsombó		Hungary	6792
110	GSK Investigational Site	Gardabaer		Iceland	210
111	GSK Investigational Site	Kopavogur		Iceland
112	GSK Investigational Site	Reykjavik		Iceland	112
113	GSK Investigational Site	Kaunas		Lithuania	LT-47144
114	GSK Investigational Site	Panevezys		Lithuania	LT-37355
115	GSK Investigational Site	Vilnius		Lithuania	LT-01205
116	GSK Investigational Site	Vilnius		Lithuania	LT-02169
117	GSK Investigational Site	Vilnius		Lithuania	LT-07156
118	GSK Investigational Site	Rotterdam		Netherlands	3011 EN
119	GSK Investigational Site	Christchurch		New Zealand	8001
120	GSK Investigational Site	Bergen		Norway	N-5021
121	GSK Investigational Site	Oslo		Norway	N-0159
122	GSK Investigational Site	Bucharest		Romania	020125
123	GSK Investigational Site	Bucharest		Romania	077190
124	GSK Investigational Site	Bucharest		Romania
125	GSK Investigational Site	Bucuresti		Romania
126	GSK Investigational Site	Blanes		Spain
127	GSK Investigational Site	Castellon		Spain
128	GSK Investigational Site	Madrid		Spain	28009
129	GSK Investigational Site	Montgat/Barcelona		Spain	08390
130	GSK Investigational Site	Valencia		Spain	46017
131	GSK Investigational Site	Valencia		Spain	46021
132	GSK Investigational Site	Valencia		Spain	46023
133	GSK Investigational Site	Valencia		Spain	46024
134	GSK Investigational Site	Göteborg		Sweden	SE-416 85
135	GSK Investigational Site	Karlskrona		Sweden	SE-371 41
136	GSK Investigational Site	Linköping		Sweden	SE-581 85
137	GSK Investigational Site	Malmö		Sweden	SE-205 02
138	GSK Investigational Site	Umeå		Sweden	SE-901 85
139	GSK Investigational Site	Örebro		Sweden	SE-702 11
140	GSK Investigational Site	Southampton	Hampshire	United Kingdom	SO14 0YG
141	GSK Investigational Site	Blackpool	Lancashire	United Kingdom	FY2 9RS
142	GSK Investigational Site	Blackpool	Lancashire	United Kingdom	FY3 7DG
143	GSK Investigational Site	Blackpool	Lancashire	United Kingdom	FY4 3AD
144	GSK Investigational Site	Bolton	Lancashire	United Kingdom	BL4 9QZ
145	GSK Investigational Site	Coventry	Warwickshire	United Kingdom	CV5 6EU
146	GSK Investigational Site	Coventry	Warwickshire	United Kingdom	CV6 4DD
147	GSK Investigational Site	Coventry	West Midlands	United Kingdom	CV2 1AX
148	GSK Investigational Site	Bradford		United Kingdom	BD5 0JD
149	GSK Investigational Site	Doncaster		United Kingdom	DN1 2EG
150	GSK Investigational Site	Leeds		United Kingdom	LS12 1JE
151	GSK Investigational Site	London		United Kingdom	SW10 9TH
152	GSK Investigational Site	Sheffield		United Kingdom	S10 2JF

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

• 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.
• 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.
• 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.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00224484
• Other Study ID Numbers: 208141/040
• First Posted: Sep 23, 2005
• Last Update Posted: Jan 7, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Herpes Simplex vaccine; Safety; Adolescents; Immunogenicity
• Additional relevant MeSH terms: Herpes Simplex; Vaccines

Study Results

Participant Flow

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	2977	1491	1487
COMPLETED	2831	1426	1425
NOT COMPLETED	146	65	62

Baseline Characteristics

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	2977	1491	1487	5955
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	13.81 (2.21)	13.81 (2.21)	13.83 (2.21)	13.81 (2.21)
Sex: Female, Male (Count of Participants)
Female	2977 100%	1491 100%	1487 100%	5955 100%
Male	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White/Caucasian	2650 89%	1340 89.9%	1330 89.4%	5320 89.3%
Arabic/North African	12 0.4%	13 0.9%	8 0.5%	33 0.6%
East/South East Asian	16 0.5%	9 0.6%	7 0.5%	32 0.5%
South Asian	6 0.2%	2 0.1%	6 0.4%	14 0.2%
American Hispanic	78 2.6%	27 1.8%	34 2.3%	139 2.3%
Not specified	58 1.9%	22 1.5%	31 2.1%	111 1.9%
Black	157 5.3%	78 5.2%	71 4.8%	306 5.1%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	2977	1491	1487
Count of Participants [Participants]	71 2.4%	42 2.8%	37 2.5%

2. Secondary Outcome

Title	Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	2970	1491	1484
Pain, Any, Dose 1	2120 71.2%	508 34.1%	247 16.6%
Pain, Grade 3, Dose 1	106 3.6%	9 0.6%	6 0.4%
Redness, Any, Dose 1	598 20.1%	125 8.4%	103 6.9%
Redness, Grade 3, Dose 1	36 1.2%	3 0.2%	0 0%
Swelling, Any, Dose 1	464 15.6%	66 4.4%	50 3.4%
Swelling, Grade 3, Dose 1	36 1.2%	1 0.1%	5 0.3%
Pain, Any, Dose 2	1685 56.6%	389 26.1%	189 12.7%
Pain, Grade 3, Dose 2	90 3%	9 0.6%	4 0.3%
Redness, Any, Dose 2	582 19.5%	95 6.4%	70 4.7%
Redness, Grade 3, Dose 2	41 1.4%	0 0%	2 0.1%
Swelling, Any, Dose 2	499 16.8%	38 2.5%	31 2.1%
Swelling, Grade 3, Dose 2	49 1.6%	0 0%	3 0.2%
Pain, Any, Dose 3	1729 58.1%	377 25.3%	161 10.8%
Pain, Grade 3, Dose 3	137 4.6%	12 0.8%	2 0.1%
Redness, Any, Dose 3	567 19%	80 5.4%	62 4.2%
Redness, Grade 3, Dose 3	51 1.7%	0 0%	0 0%
Swelling, Any, Dose 3	540 18.1%	46 3.1%	32 2.2%
Swelling, Grade 3, Dose 3	47 1.6%	0 0%	3 0.2%
Pain, Any, Across doses	2529 85%	787 52.8%	407 27.4%
Pain, Grade 3, Across doses	278 9.3%	26 1.7%	12 0.8%
Redness, Any, Across doses	1120 37.6%	222 14.9%	174 11.7%
Redness, Grade 3, Across doses	107 3.6%	3 0.2%	2 0.1%
Swelling, Any, Across doses	979 32.9%	125 8.4%	90 6.1%
Swelling, Grade 3, Across doses	108 3.6%	1 0.1%	7 0.5%

3. Secondary Outcome

Title	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	2970	1491	1484
Arthralgia, Any, Dose 1	375 12.6%	141 9.5%	122 8.2%
Arthralgia, Related, Dose 1	281 9.4%	103 6.9%	83 5.6%
Arthralgia, Grade 3, Dose 1	23 0.8%	5 0.3%	5 0.3%
Fatigue, Any, Dose 1	864 29%	377 25.3%	384 25.8%
Fatigue, Related, Dose 1	603 20.3%	246 16.5%	247 16.6%
Fatigue, Grade 3, Dose 1	51 1.7%	24 1.6%	17 1.1%
Headache, Any, Dose 1	836 28.1%	379 25.4%	395 26.6%
Headache, Related, Dose 1	530 17.8%	232 15.6%	239 16.1%
Headache, Grade 3, Dose 1	47 1.6%	18 1.2%	15 1%
Malaise, Any, Dose 1	515 17.3%	213 14.3%	225 15.1%
Malaise, Related, Dose 1	354 11.9%	138 9.3%	146 9.8%
Malaise, Grade 3, Dose 1	48 1.6%	18 1.2%	13 0.9%
Rash, Any, Dose 1	68 2.3%	29 1.9%	23 1.5%
Rash, Related, Dose 1	37 1.2%	13 0.9%	11 0.7%
Rash, Grade 3, Dose 1	1 0%	1 0.1%	2 0.1%
Temperature (Orally), Any, Dose 1	122 4.1%	59 4%	63 4.2%
Temperature(Orally), Related, Dose 1	68 2.3%	21 1.4%	31 2.1%
Temperature(Orally), Grade 3, Dose 1	6 0.2%	5 0.3%	4 0.3%
Urticaria, Any, Dose 1	27 0.9%	10 0.7%	16 1.1%
Urticaria, Related, Dose 1	18 0.6%	3 0.2%	10 0.7%
Urticaria, Grade 3, Dose 1	4 0.1%	0 0%	4 0.3%
Arthralgia, Any, Dose 2	259 8.7%	102 6.8%	54 3.6%
Arthralgia, Related, Dose 2	219 7.4%	77 5.2%	39 2.6%
Arthralgia, Grade 3, Dose 2	24 0.8%	6 0.4%	2 0.1%
Fatigue, Any, Dose 2	566 19%	226 15.2%	233 15.7%
Fatigue, Related, Dose 2	427 14.3%	157 10.5%	163 11%
Fatigue, Grade 3, Dose 2	40 1.3%	9 0.6%	8 0.5%
Headache, Any, Dose 2	579 19.4%	282 18.9%	245 16.5%
Headache, Related, Dose 2	387 13%	192 12.9%	157 10.6%
Headache, Grade 3, Dose 2	44 1.5%	15 1%	7 0.5%
Malaise, Any, Dose 2	340 11.4%	151 10.1%	124 8.3%
Malaise, Related, Dose 2	240 8.1%	103 6.9%	88 5.9%
Malaise, Grade 3, Dose 2	42 1.4%	17 1.1%	7 0.5%
Rash, Any, Dose 2	57 1.9%	16 1.1%	20 1.3%
Rash, Related, Dose 2	39 1.3%	10 0.7%	17 1.1%
Rash, Grade 3, Dose 2	2 0.1%	1 0.1%	1 0.1%
Temperature(Orally), Any, Dose 2	126 4.2%	58 3.9%	55 3.7%
Temperature(Orally), Related, Dose 2	63 2.1%	17 1.1%	27 1.8%
Temperature(Orally), Grade 3, Dose 2	8 0.3%	2 0.1%	3 0.2%
Urticaria, Any, Dose 2	14 0.5%	9 0.6%	7 0.5%
Urticaria, Related, Dose 2	11 0.4%	6 0.4%	7 0.5%
Urticaria, Grade 3, Dose 2	1 0%	1 0.1%	1 0.1%
Arthralgia, Any, Dose 3	239 8%	77 5.2%	64 4.3%
Arthralgia, Related, Dose 3	210 7.1%	56 3.8%	50 3.4%
Arthralgia, Grade 3, Dose 3	23 0.8%	2 0.1%	2 0.1%
Fatigue, Any, Dose 3	539 18.1%	213 14.3%	201 13.5%
Fatigue, Related, Dose 3	429 14.4%	158 10.6%	143 9.6%
Fatigue, Grade 3, Dose 3	32 1.1%	13 0.9%	15 1%
Headache, Any, Dose 3	513 17.2%	224 15%	199 13.4%
Headache, Related, Dose 3	376 12.6%	155 10.4%	123 8.3%
Headache, Grade 3, Dose 3	31 1%	14 0.9%	16 1.1%
Malaise, Any, Dose 3	321 10.8%	112 7.5%	118 7.9%
Malaise, Related, Dose 3	248 8.3%	77 5.2%	81 5.4%
Malaise, Grade 3, Dose 3	39 1.3%	10 0.7%	15 1%
Rash, Any, Dose 3	34 1.1%	10 0.7%	14 0.9%
Rash, Related, Dose 3	26 0.9%	3 0.2%	9 0.6%
Rash, Grade 3, Dose 3	3 0.1%	0 0%	0 0%
Temperature (Orally), Any, Dose 3	163 5.5%	55 3.7%	69 4.6%
Temperature(Orally), Related, Dose 3	84 2.8%	30 2%	25 1.7%
Temperature(Orally), Grade 3, Dose 3	11 0.4%	1 0.1%	3 0.2%
Urticaria, Any, Dose 3	16 0.5%	10 0.7%	6 0.4%
Urticaria, Related, Dose 3	11 0.4%	7 0.5%	5 0.3%
Urticaria, Grade 3, Dose 3	4 0.1%	1 0.1%	1 0.1%
Arthralgia, Any, Across doses	585 19.7%	233 15.6%	192 12.9%
Arthralgia, Related, Across doses	482 16.2%	183 12.3%	139 9.3%
Arthralgia, Grade 3, Across doses	62 2.1%	13 0.9%	9 0.6%
Fatigue, Any, Across doses	1176 39.5%	524 35.1%	526 35.4%
Fatigue, Related, Across doses	913 30.7%	382 25.6%	376 25.3%
Fatigue, Grade 3, Across doses	113 3.8%	45 3%	38 2.6%
Headache, Any, Across doses	1240 41.7%	579 38.8%	549 36.9%
Headache, Related, Across doses	875 29.4%	408 27.4%	364 24.5%
Headache, Grade 3, Across doses	113 3.8%	47 3.2%	34 2.3%
Malaise, Any, Across doses	834 28%	362 24.3%	347 23.3%
Malaise, Related, Across doses	611 20.5%	253 17%	237 15.9%
Malaise, Grade 3, Across doses	118 4%	41 2.7%	31 2.1%
Rash, Any, Across doses	141 4.7%	46 3.1%	51 3.4%
Rash, Related, Across doses	93 3.1%	20 1.3%	35 2.4%
Rash, Grade 3, Across doses	6 0.2%	2 0.1%	3 0.2%
Temperature (Orally), Any, Across doses	360 12.1%	158 10.6%	167 11.2%
Temperature (Orally), Related, Across doses	193 6.5%	65 4.4%	77 5.2%
Temperature (Orally), Grade 3, Across doses	23 0.8%	8 0.5%	10 0.7%
Urticaria, Any, Across doses	50 1.7%	25 1.7%	27 1.8%
Urticaria, Related, Across doses	37 1.2%	15 1%	21 1.4%
Urticaria, Grade 3, Across doses	9 0.3%	2 0.1%	5 0.3%

4. Secondary Outcome

Title	Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	2977	1491	1487
Any AEs	1325 44.5%	676 45.3%	667 44.9%
Grade 3 AEs	154 5.2%	68 4.6%	83 5.6%
Related AEs	313 10.5%	136 9.1%	128 8.6%

5. Secondary Outcome

Title	Number of Subjects With Unsolicited Adverse Events (AEs) With Medically Attended Visits
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	2977	1491	1487
Count of Participants [Participants]	585 19.7%	297 19.9%	298 20%

6. Secondary Outcome

Title	Number of Subjects With New Onset Chronic Diseases (NOCD)
Description	NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.
Time Frame	During the active phase (up to Month 12)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	2977	1491	1487
Count of Participants [Participants]	23 0.8%	10 0.7%	11 0.7%

7. Secondary Outcome

Title	Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	530	257	273
ALT, PRE NORMAL, M7- NORMAL	519 17.4%	249 16.7%	268 18%
ALT, PRE NORMAL, M7- BELOW	2 0.1%	1 0.1%	0 0%
ALT, PRE NORMAL, M7- ABOVE	8 0.3%	2 0.1%	4 0.3%
ALT, PRE NORMAL, M7- MISSING	1 0%	1 0.1%	1 0.1%
ALT, PRE NORMAL, M12- NORMAL	514 17.3%	246 16.5%	259 17.4%
ALT, PRE NORMAL, M12- BELOW	4 0.1%	1 0.1%	2 0.1%
ALT, PRE NORMAL, M12- ABOVE	7 0.2%	5 0.3%	4 0.3%
ALT, PRE NORMAL, M12- MISSING	4 0.1%	5 0.3%	2 0.1%
ALT, PRE BELOW, M7- NORMAL	4 0.1%	1 0.1%	3 0.2%
ALT, PRE BELOW, M7- BELOW	0 0%	3 0.2%	1 0.1%
ALT, PRE BELOW, M7- ABOVE	0 0%	0 0%	0 0%
ALT, PRE BELOW, M12- NORMAL	4 0.1%	2 0.1%	3 0.2%
ALT, PRE BELOW, M12- BELOW	0 0%	2 0.1%	0 0%
ALT, PRE BELOW, M12- ABOVE	0 0%	0 0%	0 0%
ALT, PRE BELOW, M12- MISSING	0 0%	0 0%	1 0.1%
ALT, PRE ABOVE, M7- NORMAL	4 0.1%	5 0.3%	2 0.1%
ALT, PRE ABOVE, M7- BELOW	0 0%	0 0%	0 0%
ALT, PRE ABOVE, M7- ABOVE	3 0.1%	2 0.1%	3 0.2%
ALT, PRE ABOVE, M7- MISSING	4 0.1%	3 0.2%	2 0.1%
ALT, PRE ABOVE, M12- NORMAL	4 0.1%	5 0.3%	1 0.1%
ALT, PRE ABOVE, M12- BELOW	0 0%	0 0%	0 0%
ALT, PRE ABOVE, M12- ABOVE	5 0.2%	3 0.2%	3 0.2%
ALT, PRE ABOVE, M12- MISSING	3 0.1%	1 0.1%	3 0.2%

8. Secondary Outcome

Title	Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	586	282	300
CREA, PRE NORMAL, M7- NORMAL	543 18.2%	268 18%	284 19.1%
CREA, PRE NORMAL, M7- BELOW	14 0.5%	5 0.3%	7 0.5%
CREA, PRE NORMAL, M7- ABOVE	25 0.8%	6 0.4%	9 0.6%
CREA, PRE NORMAL, M7- MISSING	4 0.1%	3 0.2%	0 0%
CREA, PRE NORMAL, M12- NORMAL	551 18.5%	257 17.2%	275 18.5%
CREA, PRE NORMAL, M12- BELOW	11 0.4%	7 0.5%	6 0.4%
CREA, PRE NORMAL, M12- ABOVE	19 0.6%	13 0.9%	10 0.7%
CREA, PRE NORMAL, M12- MISSING	2 0.1%	5 0.3%	1 0.1%
CREA, PRE BELOW, M7- NORMAL	12 0.4%	4 0.3%	3 0.2%
CREA, PRE BELOW, M7- BELOW	31 1%	19 1.3%	10 0.7%
CREA, PRE BELOW, M7- ABOVE	0 0%	0 0%	0 0%
CREA, PRE BELOW, M7- MISSING	0 0%	0 0%	2 0.1%
CREA, PRE BELOW, M12- NORMAL	21 0.7%	12 0.8%	6 0.4%
CREA, PRE BELOW, M12- BELOW	20 0.7%	10 0.7%	8 0.5%
CREA, PRE BELOW, M12- ABOVE	0 0%	0 0%	0 0%
CREA, PRE ABOVE, M7- NORMAL	15 0.5%	4 0.3%	11 0.7%
CREA, PRE ABOVE, M7- BELOW	0 0%	0 0%	0 0%
CREA, PRE ABOVE, M7- ABOVE	22 0.7%	16 1.1%	12 0.8%
CREA, PRE ABOVE, M12- NORMAL	12 0.4%	4 0.3%	7 0.5%
CREA, PRE ABOVE, M12- BELOW	0 0%	0 0%	0 0%
CREA, PRE ABOVE, M12- ABOVE	24 0.8%	17 1.1%	15 1%
CREA, PRE ABOVE, M12- MISSING	1 0%	0 0%	1 0.1%

9. Secondary Outcome

Title	Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	611	295	311
Hct, PRE NORMAL, M7- NORMAL	562 18.9%	279 18.7%	287 19.3%
Hct, PRE NORMAL, M7- BELOW	34 1.1%	11 0.7%	15 1%
Hct, PRE NORMAL, M7- ABOVE	8 0.3%	2 0.1%	3 0.2%
Hct, PRE NORMAL, M7- MISSING	7 0.2%	2 0.1%	6 0.4%
Hct, PRE NORMAL, M12- NORMAL	562 18.9%	275 18.4%	276 18.6%
Hct, PRE NORMAL, M12- BELOW	25 0.8%	11 0.7%	17 1.1%
Hct, PRE NORMAL, M12- ABOVE	12 0.4%	2 0.1%	3 0.2%
Hct, PRE NORMAL, M12- MISSING	8 0.3%	7 0.5%	7 0.5%
Hct, PRE BELOW, M7- NORMAL	20 0.7%	8 0.5%	10 0.7%
Hct, PRE BELOW, M7- BELOW	10 0.3%	5 0.3%	4 0.3%
Hct, PRE BELOW, M7- ABOVE	0 0%	0 0%	0 0%
Hct, PRE BELOW, M7- MISSING	0 0%	0 0%	1 0.1%
Hct, PRE BELOW, M12- NORMAL	17 0.6%	9 0.6%	9 0.6%
Hct, PRE BELOW, M12- BELOW	13 0.4%	4 0.3%	5 0.3%
Hct, PRE BELOW, M12- ABOVE	0 0%	0 0%	0 0%
Hct, PRE BELOW, M12- MISSING	0 0%	0 0%	1 0.1%
Hct, PRE ABOVE, M7- NORMAL	11 0.4%	8 0.5%	8 0.5%
Hct, PRE ABOVE, M7- BELOW	0 0%	0 0%	1 0.1%
Hct, PRE ABOVE, M7- ABOVE	3 0.1%	2 0.1%	1 0.1%
Hct, PRE ABOVE, M7- MISSING	0 0%	1 0.1%	0 0%
Hct, PRE ABOVE, M12- NORMAL	11 0.4%	8 0.5%	9 0.6%
Hct, PRE ABOVE, M12- BELOW	0 0%	0 0%	0 0%
Hct, PRE ABOVE, M12- ABOVE	2 0.1%	2 0.1%	0 0%
Hct, PRE ABOVE, M12- MISSING	1 0%	0 0%	0 0%

10. Secondary Outcome

Title	Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	608	296	307
PLA, PRE NORMAL, M7- NORMAL	576 19.3%	286 19.2%	292 19.6%
PLA, PRE NORMAL, M7- BELOW	5 0.2%	1 0.1%	3 0.2%
PLA, PRE NORMAL, M7- ABOVE	20 0.7%	4 0.3%	5 0.3%
PLA, PRE NORMAL, M7- MISSING	7 0.2%	3 0.2%	7 0.5%
PLA, PRE NORMAL, M12- NORMAL	579 19.4%	278 18.6%	284 19.1%
PLA, PRE NORMAL, M12- BELOW	3 0.1%	1 0.1%	0 0%
PLA, PRE NORMAL, M12- ABOVE	12 0.4%	9 0.6%	5 0.3%
PLA, PRE NORMAL, M12- MISSING	9 0.3%	8 0.5%	10 0.7%
PLA, PRE BELOW, M7- NORMAL	2 0.1%	1 0.1%	1 0.1%
PLA, PRE BELOW, M7- BELOW	5 0.2%	2 0.1%	0 0%
PLA, PRE BELOW, M7- ABOVE	0 0%	0 0%	1 0.1%
PLA, PRE BELOW, M7- MISSING	0 0%	0 0%	1 0.1%
PLA, PRE BELOW, M12- NORMAL	2 0.1%	2 0.1%	1 0.1%
PLA, PRE BELOW, M12- BELOW	4 0.1%	1 0.1%	1 0.1%
PLA, PRE BELOW, M12- ABOVE	0 0%	0 0%	0 0%
PLA, PRE BELOW, M12- MISSING	1 0%	0 0%	0 0%
PLA, PRE ABOVE, M7- NORMAL	29 1%	11 0.7%	14 0.9%
PLA, PRE ABOVE, M7- BELOW	0 0%	0 0%	0 0%
PLA, PRE ABOVE, M7- ABOVE	6 0.2%	8 0.5%	11 0.7%
PLA, PRE ABOVE, M12- NORMAL	26 0.9%	14 0.9%	18 1.2%
PLA, PRE ABOVE, M12- BELOW	0 0%	0 0%	0 0%
PLA, PRE ABOVE, M12- ABOVE	9 0.3%	4 0.3%	6 0.4%
PLA, PRE ABOVE, M12- MISSING	1 0%	0 0%	1 0.1%

11. Secondary Outcome

Title	Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	607	300	312
RBC, PRE NORMAL, M7- NORMAL	580 19.5%	284 19%	295 19.8%
RBC, PRE NORMAL, M7- BELOW	15 0.5%	8 0.5%	8 0.5%
RBC, PRE NORMAL, M7- ABOVE	6 0.2%	3 0.2%	2 0.1%
RBC, PRE NORMAL, M7- MISSING	6 0.2%	3 0.2%	7 0.5%
RBC, PRE NORMAL, M12- NORMAL	574 19.3%	281 18.8%	280 18.8%
RBC, PRE NORMAL, M12- ABOVE	17 0.6%	8 0.5%	9 0.6%
RBC, PRE NORMAL, M12- BELOW	5 0.2%	4 0.3%	9 0.6%
RBC, PRE NORMAL, M12- MISSING	7 0.2%	7 0.5%	7 0.5%
RBC, PRE BELOW, M7- NORMAL	10 0.3%	8 0.5%	7 0.5%
RBC, PRE BELOW, M7- BELOW	11 0.4%	2 0.1%	6 0.4%
RBC, PRE BELOW, M7- ABOVE	0 0%	0 0%	0 0%
RBC, PRE BELOW, M12- NORMAL	12 0.4%	7 0.5%	6 0.4%
RBC, PRE BELOW, M12- BELOW	9 0.3%	3 0.2%	7 0.5%
RBC, PRE BELOW, M12- ABOVE	0 0%	0 0%	0 0%
RBC, PRE ABOVE, M7- NORMAL	19 0.6%	7 0.5%	7 0.5%
RBC, PRE ABOVE, M7- BELOW	0 0%	0 0%	0 0%
RBC, PRE ABOVE, M7- ABOVE	5 0.2%	2 0.1%	4 0.3%
RBC, PRE ABOVE, M7- MISSING	2 0.1%	1 0.1%	0 0%
RBC, PRE ABOVE, M12- NORMAL	17 0.6%	5 0.3%	7 0.5%
RBC, PRE ABOVE, M12- BELOW	0 0%	0 0%	0 0%
RBC, PRE ABOVE, M12- ABOVE	7 0.2%	3 0.2%	1 0.1%
RBC, PRE ABOVE, M12- MISSING	2 0.1%	0 0%	1 0.1%

12. Secondary Outcome

Title	Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	651	310	329
UREA, PRE NORMAL, M7- NORMAL	632 21.2%	304 20.4%	316 21.3%
UREA, PRE NORMAL, M7- BELOW	13 0.4%	3 0.2%	9 0.6%
UREA, PRE NORMAL, M7- ABOVE	2 0.1%	2 0.1%	2 0.1%
UREA, PRE NORMAL, M7- MISSING	4 0.1%	1 0.1%	2 0.1%
UREA, PRE NORMAL, M12- NORMAL	615 20.7%	301 20.2%	304 20.4%
UREA, PRE NORMAL, M12- BELOW	18 0.6%	5 0.3%	10 0.7%
UREA, PRE NORMAL, M12- ABOVE	6 0.2%	0 0%	3 0.2%
UREA, PRE NORMAL, M12- MISSING	4 0.1%	4 0.3%	3 0.2%
UREA, PRE BELOW, M7- NORMAL	7 0.2%	7 0.5%	7 0.5%
UREA, PRE BELOW, M7- BELOW	2 0.1%	3 0.2%	2 0.1%
UREA, PRE BELOW, M7- ABOVE	0 0%	0 0%	0 0%
UREA, PRE BELOW, M12- NORMAL	10 0.3%	6 0.4%	8 0.5%
UREA, PRE BELOW, M12- BELOW	2 0.1%	3 0.2%	1 0.1%
UREA, PRE BELOW, M12- ABOVE	0 0%	0 0%	0 0%
UREA, PRE BELOW, M12- MISSING	0 0%	2 0.1%	0 0%
UREA, PRE ABOVE, M7- NORMAL	3 0.1%	3 0.2%	0 0%
UREA, PRE ABOVE, M7- BELOW	0 0%	0 0%	0 0%
UREA, PRE ABOVE, M7- ABOVE	2 0.1%	1 0.1%	1 0.1%
UREA, PRE ABOVE, M12- NORMAL	5 0.2%	3 0.2%	0 0%
UREA, PRE ABOVE, M12- BELOW	0 0%	0 0%	0 0%
UREA, PRE ABOVE, M12- ABOVE	0 0%	1 0.1%	1 0.1%

13. Secondary Outcome

Title	Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	579	274	286
WBC, PRE NORMAL, M7- NORMAL	534 17.9%	243 16.3%	253 17%
WBC, PRE NORMAL, M7- BELOW	34 1.1%	23 1.5%	17 1.1%
WBC, PRE NORMAL, M7- ABOVE	6 0.2%	4 0.3%	9 0.6%
WBC, PRE NORMAL, M7- MISSING	5 0.2%	1 0.1%	7 0.5%
WBC, PRE NORMAL, M12- NORMAL	525 17.6%	247 16.6%	251 16.9%
WBC, PRE NORMAL, M12- BELOW	31 1%	13 0.9%	17 1.1%
WBC, PRE NORMAL, M12- ABOVE	14 0.5%	9 0.6%	9 0.6%
WBC, PRE NORMAL, M12- MISSING	7 0.2%	5 0.3%	5 0.3%
WBC, PRE BELOW, M7- NORMAL	40 1.3%	20 1.3%	19 1.3%
WBC, PRE BELOW, M7- BELOW	22 0.7%	13 0.9%	17 1.1%
WBC, PRE BELOW, M7- ABOVE	0 0%	0 0%	0 0%
WBC, PRE BELOW, M7- MISSING	2 0.1%	2 0.1%	0 0%
WBC, PRE BELOW, M12- NORMAL	41 1.4%	20 1.3%	16 1.1%
WBC, PRE BELOW, M12- BELOW	20 0.7%	10 0.7%	12 0.8%
WBC, PRE BELOW, M12- ABOVE	0 0%	0 0%	1 0.1%
WBC, PRE BELOW, M12- MISSING	1 0%	2 0.1%	2 0.1%
WBC, PRE ABOVE, M7- NORMAL	6 0.2%	7 0.5%	10 0.7%
WBC, PRE ABOVE, M7- BELOW	0 0%	0 0%	0 0%
WBC, PRE ABOVE, M7- ABOVE	6 0.2%	5 0.3%	4 0.3%
WBC, PRE ABOVE, M12- NORMAL	4 0.1%	9 0.6%	11 0.7%
WBC, PRE ABOVE, M12- BELOW	0 0%	0 0%	0 0%
WBC, PRE ABOVE, M12- ABOVE	8 0.3%	3 0.2%	3 0.2%

14. Secondary Outcome

Title	Number of Subjects With Unsolicited Adverse Events (AEs) With Medically Attended Visits
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	2977	1491	1487
Count of Participants [Participants]	397 13.3%	201 13.5%	188 12.6%

15. Secondary Outcome

Title	Number of Subjects With Medically Significant Conditions (MSC)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Pooled Group
Arm/Group Description	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.	Pooled group of subjects 10-17 years of age from Havrix and Saline groups.
Measure Participants	2977	2978
Count of Participants [Participants]	69 2.3%	73 4.9%

16. Secondary Outcome

Title	Number of Subjects With New Onset Chronic Diseases (NOCD)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Pooled Group
Arm/Group Description	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.	Pooled group of subjects 10-17 years of age from Havrix and Saline groups.
Measure Participants	2977	2978
Count of Participants [Participants]	1 0%	0 0%

17. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs)
Description	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group	Pooled Group
Arm/Group Description	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.	Pooled group of subjects 10-17 years of age from Havrix and Saline groups.
Measure Participants	2977	2978
Count of Participants [Participants]	90 3%	100 6.7%

18. Secondary Outcome

Title	Anti-glycoprotein D (Anti-gD) Antibody Concentrations
Description	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	gD2-AS04 Group
Arm/Group Description	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.
Measure Participants	386
HSV1-2-, PRE	23.0
HSV1-2-, M7	7808.6
HSV1-2-, M12	2408.9
HSV1+2-, PRE	1702.1
HSV1+2-, M7	10344.1
HSV1+2-, M12	6411.8

19. Secondary Outcome

Title	Anti-deacylated Monophosphoryl Lipid A (Anti-MPL) Antibody Concentrations
Description	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

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	gD2-AS04 Group	Havrix Group	Saline Group
Arm/Group Description	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.	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.	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.
Measure Participants	303	128	151
Anti-MPL, PRE	195.2	168.3	198.4
Anti-MPL, M7	801.9	152.7	190.7
Anti-MPL, M12	537.4	193.8	232.9

Adverse Events

Time Frame	Serious Adverse Events: -Group GD2-AS04, Group Havrix and Group Saline: during the active study period (Month 0 - 12). -GD2-AS04 (ESFU) Group and Pooled Group: during the combined active study period and the ESFU period (Month 0 - 18). Other Adverse Events: -Solicited local/general symptoms: during the 7-day post-vaccination period. -Unsolicited Adverse Events: during the 30-day post-vaccination.
Adverse Event Reporting Description	The solicited local and general symptoms were only collected for those subjects who filled in their symptom sheets. Other Adverse Events were not collected during the ESFU period, hence resulting in zero participants at risk for GD2-AS04 (ESFU) Group and Pooled Group.
Arm/Group Title	Group GD2-AS04		Group Havrix		Group Saline		GD2-AS04 (ESFU) Group		Pooled Group
Arm/Group Description	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.		Female subjects aged 10-17 years, who received 3 doses of Havrix™ vaccine, which were administered intramuscularly in the deltoid region of the non-dominant arm according to a 0, 1, 6 months schedule.		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.		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.		Pooled group of subjects 10-17 years of age from Havrix and Saline groups, included in the Extended Safety Follow Up (ESFU) period.
All Cause Mortality
	Group GD2-AS04		Group Havrix		Group Saline		GD2-AS04 (ESFU) Group		Pooled Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		0/2977 (0%)		0/2978 (0%)
Serious Adverse Events
	Group GD2-AS04		Group Havrix		Group Saline		GD2-AS04 (ESFU) Group		Pooled Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/2977 (2.4%)		42/1491 (2.8%)		37/1487 (2.5%)		90/2977 (3%)		100/2978 (3.4%)
Blood and lymphatic system disorders
Anaemia	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		2/2978 (0.1%)
Lymphadenitis	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Cardiac disorders
Sinus bradycardia	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Tachycardia	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Endocrine disorders
Hyperthyroidism	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Eye disorders
Maculopathy	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Gastrointestinal disorders
Abdominal pain	2/2977 (0.1%)		0/1491 (0%)		1/1487 (0.1%)		2/2977 (0.1%)		2/2978 (0.1%)
Abdominal pain lower	1/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		1/2977 (0%)		1/2978 (0%)
Abdominal pain upper	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Colitis ulcerative	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Gastritis	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		2/2978 (0.1%)
Gastrointestinal haemorrhage	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Inguinal hernia	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Lip swelling	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Peritonitis	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Abdominal discomfort	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Gastrointestinal disorder	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
General disorders
Cyst	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Granuloma	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Hypothermia	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Hepatobiliary disorders
Cholelithiasis	1/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		1/2977 (0%)		1/2978 (0%)
Immune system disorders
Hypersensitivity	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Infections and infestations
Acute tonsillitis	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Appendicitis	9/2977 (0.3%)		3/1491 (0.2%)		3/1487 (0.2%)		11/2977 (0.4%)		8/2978 (0.3%)
Bronchitis	2/2977 (0.1%)		0/1491 (0%)		0/1487 (0%)		2/2977 (0.1%)		0/2978 (0%)
Carbuncle	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Cellulitis	1/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		1/2977 (0%)		1/2978 (0%)
Chronic tonsillitis	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Folliculitis	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Gastroenteritis	1/2977 (0%)		1/1491 (0.1%)		1/1487 (0.1%)		1/2977 (0%)		2/2978 (0.1%)
Gastroenteritis viral	2/2977 (0.1%)		0/1491 (0%)		0/1487 (0%)		2/2977 (0.1%)		0/2978 (0%)
Herpes zoster	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Infectious mononucleosis	2/2977 (0.1%)		0/1491 (0%)		1/1487 (0.1%)		3/2977 (0.1%)		1/2978 (0%)
Influenza	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Meningitis viral	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		1/2978 (0%)
Peritonsillar abscess	2/2977 (0.1%)		1/1491 (0.1%)		0/1487 (0%)		2/2977 (0.1%)		1/2978 (0%)
Pharyngotonsillitis	1/2977 (0%)		2/1491 (0.1%)		0/1487 (0%)		1/2977 (0%)		2/2978 (0.1%)
Pilonidal cyst	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Pneumonia	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		2/2978 (0.1%)
Pyelonephritis	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Salpingitis	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Sinusitis	1/2977 (0%)		2/1491 (0.1%)		0/1487 (0%)		1/2977 (0%)		3/2978 (0.1%)
Tonsillitis	0/2977 (0%)		1/1491 (0.1%)		1/1487 (0.1%)		0/2977 (0%)		3/2978 (0.1%)
Tracheobronchitis	0/2977 (0%)		1/1491 (0.1%)		1/1487 (0.1%)		0/2977 (0%)		2/2978 (0.1%)
Urinary tract infection	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		1/2977 (0%)		2/2978 (0.1%)
Viral upper respiratory tract infection	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Cystitis	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Encephalitis viral	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Fusarium infection	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Gastroenteritis rotavirus	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Incision site infection	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Meningitis aseptic	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Pyelonephritis acute	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Salmonellosis	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Acute sinusitis	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Injury, poisoning and procedural complications
Animal bite	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Carbon monoxide poisoning	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Cervical vertebral fracture	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Clavicle fracture	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Concussion	2/2977 (0.1%)		0/1491 (0%)		0/1487 (0%)		3/2977 (0.1%)		0/2978 (0%)
Contusion	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Fracture	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Hand fracture	1/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		1/2977 (0%)		1/2978 (0%)
Humerus fracture	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Jaw fracture	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Joint dislocation	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		2/2977 (0.1%)		0/2978 (0%)
Joint injury	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Ligament rupture	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		2/2977 (0.1%)		0/2978 (0%)
Lower limb fracture	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Overdose	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Patella fracture	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Poisoning	1/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		1/2977 (0%)		1/2978 (0%)
Road traffic accident	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Skin laceration	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Spinal compression fracture	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Tibia fracture	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Meniscus lesion	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Therapeutic agent toxicity	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Vertebral injury	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Wound	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		0/2977 (0%)		2/2978 (0.1%)
Metabolism and nutrition disorders
Anorexia	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Dehydration	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		1/2977 (0%)		1/2978 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian adenoma	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Nervous system disorders
Convulsion	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Dyskinesia	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Epilepsy	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Facial paresis	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Headache	2/2977 (0.1%)		0/1491 (0%)		0/1487 (0%)		2/2977 (0.1%)		0/2978 (0%)
Migraine	0/2977 (0%)		0/1491 (0%)		2/1487 (0.1%)		0/2977 (0%)		2/2978 (0.1%)
Neuropathy peripheral	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Painful response to normal stimuli	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Peripheral nerve lesion	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Syncope	2/2977 (0.1%)		0/1491 (0%)		0/1487 (0%)		2/2977 (0.1%)		0/2978 (0%)
Brain oedema	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Paraparesis	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Syncope vasovagal	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/2977 (0%)		2/1491 (0.1%)		4/1487 (0.3%)		1/2977 (0%)		7/2978 (0.2%)
Abortion spontaneous incomplete	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Abortion spontaneous complete	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Psychiatric disorders
Abnormal behaviour	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Agression	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		2/2978 (0.1%)
Alcohol abuse	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Anorexia nervosa	1/2977 (0%)		1/1491 (0.1%)		1/1487 (0.1%)		1/2977 (0%)		2/2978 (0.1%)
Bipolar disorder	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		2/2977 (0.1%)		2/2978 (0.1%)
Depression	6/2977 (0.2%)		0/1491 (0%)		2/1487 (0.1%)		8/2977 (0.3%)		5/2978 (0.2%)
Drug abuse	0/2977 (0%)		2/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		2/2978 (0.1%)
Hallucination	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Intentional self-injury	1/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		1/2977 (0%)		1/2978 (0%)
Mental disorder	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Psychotic disorder	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Schizophrenia	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Suicidal ideation	2/2977 (0.1%)		1/1491 (0.1%)		1/1487 (0.1%)		2/2977 (0.1%)		2/2978 (0.1%)
Suicide attempt	5/2977 (0.2%)		1/1491 (0.1%)		0/1487 (0%)		5/2977 (0.2%)		1/2978 (0%)
Anxiety disorder	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Conversion disorder	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Renal and urinary disorders
Nephrolithiasis	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Nephrotic syndrome	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Reproductive system and breast disorders
Dysmenorrhoea	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		1/2978 (0%)
Haemorrhagic ovarian cyst	0/2977 (0%)		0/1491 (0%)		1/1487 (0.1%)		0/2977 (0%)		1/2978 (0%)
Ovarian cyst	1/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		1/2977 (0%)		1/2978 (0%)
Ovarian cyst ruptured	2/2977 (0.1%)		1/1491 (0.1%)		0/1487 (0%)		2/2977 (0.1%)		1/2978 (0%)
Endometriosis	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Hyperventilation	2/2977 (0.1%)		0/1491 (0%)		0/1487 (0%)		2/2977 (0.1%)		0/2978 (0%)
Hypoxia	1/2977 (0%)		0/1491 (0%)		0/1487 (0%)		1/2977 (0%)		0/2978 (0%)
Pneumomediastinum	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Pneumothorax	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Dyspnoea	0/2977 (0%)		0/1491 (0%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		0/2977 (0%)		1/2978 (0%)
Urticaria	1/2977 (0%)		1/1491 (0.1%)		0/1487 (0%)		1/2977 (0%)		1/2978 (0%)
Other (Not Including Serious) Adverse Events
	Group GD2-AS04		Group Havrix		Group Saline		GD2-AS04 (ESFU) Group		Pooled Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2718/2977 (91.3%)		1210/1491 (81.2%)		1082/1487 (72.8%)		0/0 (NaN)		0/0 (NaN)
General disorders
Pain	2529/2970 (85.2%)		787/1491 (52.8%)		407/1484 (27.4%)		407/0 (Infinity)		407/0 (Infinity)
Redness	1120/2970 (37.7%)		222/1491 (14.9%)		174/1484 (11.7%)		174/0 (Infinity)		174/0 (Infinity)
Swelling	979/2970 (33%)		125/1491 (8.4%)		90/1484 (6.1%)		90/0 (Infinity)		90/0 (Infinity)
Arthralgia	585/2970 (19.7%)		233/1491 (15.6%)		192/1484 (12.9%)		192/0 (Infinity)		192/0 (Infinity)
Fatigue	1176/2970 (39.6%)		524/1491 (35.1%)		526/1484 (35.4%)		526/0 (Infinity)		526/0 (Infinity)
Headache	1240/2970 (41.8%)		579/1491 (38.8%)		549/1484 (37%)		549/0 (Infinity)		549/0 (Infinity)
Malaise	834/2970 (28.1%)		362/1491 (24.3%)		347/1484 (23.4%)		347/0 (Infinity)		347/0 (Infinity)
Temperature (Orally)	360/2970 (12.1%)		158/1491 (10.6%)		167/1484 (11.3%)		167/0 (Infinity)		167/0 (Infinity)
Infections and infestations
Nasopharyngitis	147/2977 (4.9%)		75/1491 (5%)		81/1487 (5.4%)		81/0 (Infinity)		81/0 (Infinity)
Upper respiratory tract infection	151/2977 (5.1%)		50/1491 (3.4%)		69/1487 (4.6%)		69/0 (Infinity)		69/0 (Infinity)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.