Trial Outcomes & Findings for Evaluation of Immunogenicity and Safety of Human Papillomavirus (HPV) Vaccine Co-administered With Another Vaccine in Healthy Female Subjects (NCT NCT00652938)

NCT ID: NCT00652938

Last Updated: 2018-08-17

Results Overview

Only groups which had received the HBV vaccine were included in the analysis. Subjects included were seronegative for anti-HBs (antibody titer \< 3.3 milli International Units per milliliter (mIU/mL)) prior to vaccination. Anti-HBs antibody cut-off value for seroprotection assessed included 10 mIU/mL.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 744 participants
• Primary outcome timeframe: Month 7
• Results posted on: 2018-08-17

Participant Flow

While the total numbers of subjects enrolled in the study was 744, the total number of subjects that entered the study was 741. The remaining 3 subjects received a subject number but no vaccine dose and were therefore excluded from the analysis and group assignment.

Participant milestones

Measure	Cervarix&Engerix Group Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Overall Study STARTED	247	247	247
Overall Study COMPLETED	246	240	242
Overall Study NOT COMPLETED	1	7	5

Reasons for withdrawal

Measure	Cervarix&Engerix Group Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Overall Study Adverse Event	1	0	2
Overall Study Withdrawal by Subject	0	6	1
Overall Study Lost to Follow-up	0	0	2
Overall Study fear of blood sampling	0	1	0

Baseline Characteristics

Evaluation of Immunogenicity and Safety of Human Papillomavirus (HPV) Vaccine Co-administered With Another Vaccine in Healthy Female Subjects

Baseline characteristics by cohort

Measure	Cervarix&Engerix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=247 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Total n=741 Participants Total of all reporting groups
Age, Continuous	11.4 years STANDARD_DEVIATION 2.17 • n=5 Participants	11.3 years STANDARD_DEVIATION 2.14 • n=7 Participants	11.4 years STANDARD_DEVIATION 2.17 • n=5 Participants	11.4 years STANDARD_DEVIATION 2.16 • n=4 Participants
Sex: Female, Male Female	247 Participants n=5 Participants	247 Participants n=7 Participants	247 Participants n=5 Participants	741 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Month 7

Population: The analysis was performed on the According-to-Protocol (ATP) Cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Only groups which had received the HBV vaccine were included in the analysis.

Subjects included were seronegative for anti-HBs (antibody titer < 3.3 milli International Units per milliliter (mIU/mL)) prior to vaccination.

Anti-HBs antibody cut-off value for seroprotection assessed included 10 mIU/mL.

Outcome measures

Measure	Cervarix&Engerix Group n=194 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=181 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects With Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Value for Seroprotection	190 Participants	—	181 Participants

PRIMARY outcome

Timeframe: Month 7

Population: The analysis was performed on the According-to-Protocol (ATP) Cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Only groups which had received the HPV vaccine were included in the analysis.

Anti-HPV-16 antibody cut-off value assessed included 8 Enzyme-linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL) and anti-HPV-18 antibody cut-off value assessed included 7 EL.U/mL.

Subjects included were seronegative for anti-HPV-16 (antibody titer < 8 EL.U/mL) and anti-HPV-18 (antibody titer < 7 EL.U/mL) prior to vaccination.

Outcome measures

Measure	Cervarix&Engerix Group n=207 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=202 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects With Anti-human Papillomavirus 16 and 18 (Anti-HPV-16 and Anti-HPV-18) Antibody Concentrations Above the Cut-off Value for Seroconversion Anti-HPV-18	199 Participants	202 Participants	—
Number of Subjects With Anti-human Papillomavirus 16 and 18 (Anti-HPV-16 and Anti-HPV-18) Antibody Concentrations Above the Cut-off Value for Seroconversion Anti-HPV-16	205 Participants	200 Participants	—

PRIMARY outcome

Timeframe: Month 7

Population: The analysis was performed on the According-to-Protocol (ATP) Cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Antibody titers for Anti-HPV-16 and Anti-HPV-18 are expressed as Geometric Mean Titers (GMTs).

Only groups which had received the HPV vaccine were included in the analysis.

Subjects included were seronegative for anti-HPV-16 (antibody titer < 8 EL.U/mL) and anti-HPV-18 (antibody titer < 7 EL.U/mL) prior to vaccination.

Outcome measures

Measure	Cervarix&Engerix Group n=207 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=202 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Anti-HPV-16/18 Antibody Titres Anti-HPV-16	19819.8 EL.U/mL Interval 16856.9 to 23303.6	21712.6 EL.U/mL Interval 19460.2 to 24225.6	—
Anti-HPV-16/18 Antibody Titres Anti-HPV-18	8835.1 EL.U/mL Interval 7636.3 to 10222.1	8838.6 EL.U/mL Interval 7948.5 to 9828.4	—

SECONDARY outcome

Timeframe: Month 7

Population: The analysis was performed on the According-to-Protocol (ATP) Cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Only groups which had received the HBV vaccine were included in the analysis.

Subjects included were seronegative for anti-HBs (antibody titer < 3.3 mIU/mL) prior to vaccination.

Anti-HBs antibody cut-off value for seroconversion assessed included 3.3 mIU/mL.

Outcome measures

Measure	Cervarix&Engerix Group n=194 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=181 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects With Anti-HBs Antibody Concentrations Above the Cut-off Value for Seroconversion	192 Participants	—	181 Participants

SECONDARY outcome

Timeframe: Month 7

Population: The analysis was performed on the According-to-Protocol (ATP) Cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Antibody titers for anti-HBs are given as Geometric Mean Titers (GMTs) in mIU/mL.

Only groups which had received the HBV vaccine were included in the analysis.

Subjects included were seronegative for anti-HBs (antibody titer < 3.3 mIU/mL) prior to vaccination.

Outcome measures

Measure	Cervarix&Engerix Group n=194 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=181 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Anti-HBs Antibody Titres	1280.9 mIU/mL Interval 973.3 to 1685.7	—	3107.7 mIU/mL Interval 2473.1 to 3905.1

SECONDARY outcome

Timeframe: Month 2

Population: The analysis was performed on the According-to-Protocol (ATP) Cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Only groups which had received the HPV vaccine were included in the analysis.

Anti-HPV-16 antibody cut-off value assessed included 8 Enzyme-linked Immunosorbent Assay (ELISA) units per milliliter (EL.U/mL) and anti-HPV-18 antibody cut-off value assessed included 7 EL.U/mL.

Subjects included were seronegative for anti-HPV-16 (antibody titer < 8 EL.U/mL) and anti-HPV-18 (antibody titer < 7 EL.U/mL) prior to vaccination.

Outcome measures

Measure	Cervarix&Engerix Group n=207 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=201 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects With Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations Above the Cut-off Value for Seroconversion Anti-HPV-16	207 Participants	199 Participants	—
Number of Subjects With Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations Above the Cut-off Value for Seroconversion Anti-HPV-18	200 Participants	201 Participants	—

SECONDARY outcome

Timeframe: Month 2

Population: The analysis was performed on the According-to-Protocol (ATP) Cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Antibody titers for Anti-HPV-16 and Anti-HPV-18 are expressed as Geometric Mean Titers (GMTs).

Only groups which had received the HPV vaccine were included in the analysis.

Subjects included were seronegative for anti-HPV-16 (antibody titer < 8 EL.U/mL) and anti-HPV-18 (antibody titer < 7 EL.U/mL) prior to vaccination.

Outcome measures

Measure	Cervarix&Engerix Group n=207 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=201 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Anti-HPV-16/18 Antibody Titres Anti-HPV-16	4894.7 EL.U/mL Interval 4472.5 to 5356.7	5069.2 EL.U/mL Interval 4581.2 to 5609.1	—
Anti-HPV-16/18 Antibody Titres Anti-HPV-18	4790.4 EL.U/mL Interval 4338.9 to 5288.8	4663.8 EL.U/mL Interval 4228.2 to 5144.3	—

SECONDARY outcome

Timeframe: Month 2

Population: The analysis was performed on the According-to-Protocol (ATP) Cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Only groups which had received the HBV vaccine were included in the analysis.

Subjects included were seronegative for anti-HBs (antibody titer < 3.3 mIU/mL) prior to vaccination.

Anti-HBs antibody cut-off value for seroconversion assessed included 3.3 mIU/mL.

Outcome measures

Measure	Cervarix&Engerix Group n=194 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=178 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects With Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Value for Seroconversion	165 Participants	—	168 Participants

SECONDARY outcome

Timeframe: Month 2

Population: The analysis was performed on the According-to-Protocol (ATP) Cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Only groups which had received the HBV vaccine were included in the analysis.

Subjects included were seronegative for anti-HBs (antibody titer < 3.3 milli International Units per milliliter (mIU/mL)) prior to vaccination vaccination.

Anti-HBs antibody cut-off value for seroprotection assessed included 10 mIU/mL.

Outcome measures

Measure	Cervarix&Engerix Group n=194 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=178 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects With Anti-Hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Above the Cut-off Value for Seroprotection	128 Participants	—	142 Participants

SECONDARY outcome

Timeframe: Month 2

Population: The analysis was performed on the According-to-Protocol (ATP) Cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Anti-HBs antibody titers are given as GMTs in mIU/mL.

Only groups which had received the HBV vaccine were included in the analysis.

Subjects included were seronegative for anti-HBs (antibody titer < 3.3 mIU/mL) prior to vaccination.

Outcome measures

Measure	Cervarix&Engerix Group n=194 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=178 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Anti-HBs Antibody Titers	13.6 mIU/mL Interval 11.4 to 16.2	—	26.9 mIU/mL Interval 22.1 to 32.8

SECONDARY outcome

Timeframe: During the 7-day period (Days 0 - 6) following vaccination

Population: Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

Solicited local symptoms included injection site pain, redness and swelling.

Any solicited local symptom is occurence of a symptom regardless of its intensity.

Outcome measures

Measure	Cervarix&Engerix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=245 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=246 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Any Solicited Local Symptoms Pain	244 Participants	238 Participants	182 Participants
Number of Subjects Reporting Any Solicited Local Symptoms Redness	122 Participants	127 Participants	63 Participants
Number of Subjects Reporting Any Solicited Local Symptoms Swelling	120 Participants	111 Participants	47 Participants

SECONDARY outcome

Timeframe: During the 7-day period (Days 0-6) following vaccination

Population: Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

Solicited local symptoms include injection site pain, redness and swelling.

Grade 3 pain is pain that prevented normal everyday activities. Grade 3 redness is redness that was > 50 mm. Grade 3 swelling is swelling that was > 50 mm.

Outcome measures

Measure	Cervarix&Engerix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=245 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=246 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Grade 3 Solicited Local Symptoms Pain	54 Participants	35 Participants	4 Participants
Number of Subjects Reporting Grade 3 Solicited Local Symptoms Swelling	17 Participants	13 Participants	1 Participants
Number of Subjects Reporting Grade 3 Solicited Local Symptoms Redness	12 Participants	5 Participants	1 Participants

SECONDARY outcome

Timeframe: During the 7-day (Days 0-6) period following vaccination.

Population: Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

Solicited general symptoms included arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, temperature in degrees celsius (axillary) and urticaria.

Any solicited general symptom is the occurence of the symptom regardless of its intensity or relationship to study vaccination.

Outcome measures

Measure	Cervarix&Engerix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=245 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=246 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Any Solicited General Symptoms Arthralgia	31 Participants	23 Participants	26 Participants
Number of Subjects Reporting Any Solicited General Symptoms Temperature	32 Participants	23 Participants	36 Participants
Number of Subjects Reporting Any Solicited General Symptoms Fatigue	130 Participants	107 Participants	104 Participants
Number of Subjects Reporting Any Solicited General Symptoms Gastrointestinal	65 Participants	67 Participants	70 Participants
Number of Subjects Reporting Any Solicited General Symptoms Headache	136 Participants	131 Participants	129 Participants
Number of Subjects Reporting Any Solicited General Symptoms Myalgia	55 Participants	55 Participants	53 Participants
Number of Subjects Reporting Any Solicited General Symptoms Rash	10 Participants	14 Participants	11 Participants
Number of Subjects Reporting Any Solicited General Symptoms Urticaria	5 Participants	5 Participants	6 Participants

SECONDARY outcome

Timeframe: During the 7-day (Days 0-6) period following vaccination

Population: Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

Solicited general symptoms included arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, temperature in degrees celsius (axillary) and urticaria.

Grade 3 arthralgia, fatigue, gastrointestinal, headache, myalgia and rash were symptoms that prevented normal activity.

Grade 3 temperature was temperature > 39 degrees Celsius. Grade 3 urticaria was urticaria distributed on at least 4 body areas.

Outcome measures

Measure	Cervarix&Engerix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=245 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=246 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Grade 3 Solicited General Symptoms Headache	13 Participants	11 Participants	4 Participants
Number of Subjects Reporting Grade 3 Solicited General Symptoms Arthralgia	1 Participants	0 Participants	0 Participants
Number of Subjects Reporting Grade 3 Solicited General Symptoms Fatigue	8 Participants	8 Participants	9 Participants
Number of Subjects Reporting Grade 3 Solicited General Symptoms Myalgia	2 Participants	2 Participants	1 Participants
Number of Subjects Reporting Grade 3 Solicited General Symptoms Rash	0 Participants	1 Participants	0 Participants
Number of Subjects Reporting Grade 3 Solicited General Symptoms Temperature	3 Participants	2 Participants	3 Participants
Number of Subjects Reporting Grade 3 Solicited General Symptoms Urticaria	0 Participants	0 Participants	1 Participants
Number of Subjects Reporting Grade 3 Solicited General Symptoms Gastrointestinal	4 Participants	6 Participants	8 Participants

SECONDARY outcome

Timeframe: During the 7-day period (Days 0 - 6) following vaccination

Population: Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

Solicited general symptoms included arthralgia, fatigue, gastrointestinal, headache, myalgia, rash, temperature in degrees celsius (axillary) and urticaria.

Related solicited general symptoms were those symptoms assessed by the investigators as related to the study vaccination.

Outcome measures

Measure	Cervarix&Engerix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=245 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=246 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Related Solicited General Symptoms Arthralgia	18 Participants	16 Participants	12 Participants
Number of Subjects Reporting Related Solicited General Symptoms Fatigue	89 Participants	70 Participants	51 Participants
Number of Subjects Reporting Related Solicited General Symptoms Gastrointestinal	35 Participants	40 Participants	25 Participants
Number of Subjects Reporting Related Solicited General Symptoms Headache	77 Participants	71 Participants	57 Participants
Number of Subjects Reporting Related Solicited General Symptoms Myalgia	40 Participants	40 Participants	20 Participants
Number of Subjects Reporting Related Solicited General Symptoms Rash	8 Participants	8 Participants	4 Participants
Number of Subjects Reporting Related Solicited General Symptoms Temperature	13 Participants	10 Participants	6 Participants
Number of Subjects Reporting Related Solicited General Symptoms Urticaria	4 Participants	4 Participants	2 Participants

SECONDARY outcome

Timeframe: During the 30-day period (Days 0 - 29) following any vaccination

Population: Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

Unsolicited AE covers any AE 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.

Grade 3 AE was an AE that prevented normal activities. Related AE was an AE that was assessed by the investigator as related to the study vaccination.

Outcome measures

Measure	Cervarix&Engerix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=247 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Any, Grade 3 and Causally Related to Vaccination Unsolicited Adverse Events (AEs) Related AEs	43 Participants	19 Participants	25 Participants
Number of Subjects Reporting Any, Grade 3 and Causally Related to Vaccination Unsolicited Adverse Events (AEs) Any AEs	130 Participants	99 Participants	99 Participants
Number of Subjects Reporting Any, Grade 3 and Causally Related to Vaccination Unsolicited Adverse Events (AEs) Grade 3 AEs	19 Participants	19 Participants	16 Participants

SECONDARY outcome

Timeframe: Throughout the active phase of the study (up to Month 7).

Population: Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

Related SAEs were SAEs assessed by the investigators as related to the vaccination.

• Grade 3 SAEs were not assessed.

Outcome measures

Measure	Cervarix&Engerix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=247 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Any and Causally Related to Vaccination Serious Adverse Events (SAEs) Any	2 Participants	1 Participants	0 Participants
Number of Subjects Reporting Any and Causally Related to Vaccination Serious Adverse Events (SAEs) Related	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Throughout the safety follow-up (month 7 up to Month 12).

Population: Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.

• Grade 3 SAEs were not assessed.

Outcome measures

Measure	Cervarix&Engerix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=247 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Any and Causally Related to Vaccination SAEs Any	1 Participants	1 Participants	1 Participants
Number of Subjects Reporting Any and Causally Related to Vaccination SAEs Related	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Throughout the active phase of the study (up to Month 7)

Population: Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

Medically significant conditions (i.e., AEs prompting emergency room or physician visits that are not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that are not related to common diseases).

Outcome measures

Measure	Cervarix&Engerix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=247 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Medically Significant Conditions	31 Participants	28 Participants	22 Participants

SECONDARY outcome

Timeframe: Throughout the safety follow-up (month 7 up to Month 12)

Population: Analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects for whom data were available.

Medically significant conditions (i.e., AEs prompting emergency room or physician visits that are not (1) related to common diseases or (2) routine visits for physical examination or vaccination, or SAEs that are not related to common diseases).

Outcome measures

Measure	Cervarix&Engerix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=247 Participants Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=247 Participants Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Medically Significant Conditions	0 Participants	2 Participants	2 Participants

Adverse Events

Cervarix&Engerix Group

Serious events: 3 serious events

Other events: 246 other events

Deaths: 0 deaths

Cervarix Group

Serious events: 2 serious events

Other events: 239 other events

Deaths: 0 deaths

Engerix Group

Serious events: 1 serious events

Other events: 222 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cervarix&Engerix Group n=247 participants at risk Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=247 participants at risk Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=247 participants at risk Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
Renal and urinary disorders Nephrolithiasis	0.00% 0/247	0.40% 1/247	0.00% 0/247
Reproductive system and breast disorders Ovarian cyst	0.40% 1/247	0.00% 0/247	0.00% 0/247
Injury, poisoning and procedural complications Traumatic brain injury	0.40% 1/247	0.00% 0/247	0.00% 0/247
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/247	0.00% 0/247	0.40% 1/247
Infections and infestations Appendicitis	0.40% 1/247	0.00% 0/247	0.00% 0/247
Injury, poisoning and procedural complications Forearm fracture	0.00% 0/247	0.40% 1/247	0.00% 0/247

Other adverse events

Measure	Cervarix&Engerix Group n=247 participants at risk Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) co-administered with Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.	Cervarix Group n=247 participants at risk Subjects received 3 doses of Cervarix™ (Human Papillomavirus \[HPV\] vaccine) according to a 0, 1, 6-month schedule.	Engerix Group n=247 participants at risk Subjects received 3 doses of Engerix™ (Hepatitis B \[HBV\] vaccine) according to a 0, 1, 6-month schedule.
General disorders Pain	98.8% 244/247	96.4% 238/247	73.7% 182/247
General disorders Redness	49.4% 122/247	51.4% 127/247	25.5% 63/247
General disorders Swelling	48.6% 120/247	44.9% 111/247	19.0% 47/247
General disorders Arthralgia	12.6% 31/247	9.3% 23/247	10.5% 26/247
General disorders Fatigue	52.6% 130/247	43.3% 107/247	42.1% 104/247
General disorders Gastrointestinal	26.3% 65/247	27.1% 67/247	28.3% 70/247
General disorders Headache	6.9% 17/247	7.7% 19/247	3.6% 9/247
General disorders Myalgia	22.3% 55/247	22.3% 55/247	21.5% 53/247
General disorders Rash	4.0% 10/247	5.7% 14/247	4.5% 11/247
General disorders Temperature	13.0% 32/247	9.3% 23/247	14.6% 36/247
General disorders Nasopharyngitis	11.7% 29/247	10.9% 27/247	10.5% 26/247
General disorders Oropharyngeal pain	5.3% 13/247	5.3% 13/247	2.8% 7/247

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER