Trial Outcomes & Findings for Immunogenicity and Safety of GlaxoSmithKline Biologicals' Huma Papillomavirus (HPV) Vaccine 580299 in Healthy Females 15 - 25 Years of Age (NCT NCT00552279)

Last Updated: 2018-06-25

Results Overview

Seroconversion is defined as the appearance of anti-HPV-16 and/or anti- HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination. Cut-off values were 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti- HPV-18 antibodies.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

805 participants

Primary outcome timeframe

One month after the third vaccine dose

Results posted on

2018-06-25

Participant Flow

A total of 805 subjects were enrolled and 804 subjects were vaccinated and included in the analyses.

Participant milestones

Participant milestones
Measure	Cervarix-12 Group Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Overall Study STARTED	403	401
Overall Study COMPLETED	389	398
Overall Study NOT COMPLETED	14	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Cervarix-12 Group Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Overall Study Adverse Event	0	1
Overall Study Withdrawal by Subject	12	1
Overall Study Lost to Follow-up	1	0
Overall Study Other	1	1

Baseline Characteristics

Immunogenicity and Safety of GlaxoSmithKline Biologicals' Huma Papillomavirus (HPV) Vaccine 580299 in Healthy Females 15 - 25 Years of Age

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cervarix-12 Group n=403 Participants Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=401 Participants Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.	Total n=804 Participants Total of all reporting groups
Age, Continuous	18.6 years STANDARD_DEVIATION 2.98 • n=5 Participants	18.7 years STANDARD_DEVIATION 3.13 • n=7 Participants	18.6 years STANDARD_DEVIATION 3.05 • n=5 Participants
Sex: Female, Male Female	403 Participants n=5 Participants	401 Participants n=7 Participants	804 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: One month after the third vaccine dose

Population: Analysis was performed on initially seronegative subjects from the According-to-Protocol (ATP) cohort for analysis of immunogenicity

Outcome measures

Outcome measures
Measure	Cervarix-12 Group n=346 Participants Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=346 Participants Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies Anti-HPV-16	337 Participants	342 Participants
Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies Anti-HPV-18	345 Participants	346 Participants

PRIMARY outcome

Timeframe: One month after the third vaccine dose

Population: Analysis was performed on initially seronegative subjects from the ATP cohort for analysis of immunogenicity

Titer given as geometric mean titer (GMT).

Outcome measures

Outcome measures
Measure	Cervarix-12 Group n=346 Participants Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=346 Participants Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Titer of Anti-HPV-16 and Anti-HPV-18 Antibodies Anti-HPV-16	11337.2 EL.U/mL Interval 10238.2 to 12554.1	10050.9 EL.U/mL Interval 9180.9 to 11003.3
Titer of Anti-HPV-16 and Anti-HPV-18 Antibodies Anti-HPV-18	4526.7 EL.U/mL Interval 4110.1 to 4985.6	3879.9 EL.U/mL Interval 3532.7 to 4261.2

SECONDARY outcome

Timeframe: One month after the second vaccine dose

Population: Analysis was performed on initially seronegative subjects from the ATP cohort for analysis of immunogenicity

Outcome measures

Outcome measures
Measure	Cervarix-12 Group n=346 Participants Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=346 Participants Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies Anti-HPV-16	337 Participants	342 Participants
Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies Anti-HPV-18	346 Participants	346 Participants

SECONDARY outcome

Timeframe: One month after the second vaccine dose

Population: Analysis was performed on initially seronegative subjects from the ATP cohort for analysis of immunogenicity

Titer given as GMT.

Outcome measures

Outcome measures
Measure	Cervarix-12 Group n=346 Participants Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=346 Participants Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Titer of Anti-HPV-16 and Anti-HPV-18 Antibodies Anti-HPV-16	3307.0 EL.U/mL Interval 3051.0 to 3584.5	3184.1 EL.U/mL Interval 2938.3 to 3450.5
Titer of Anti-HPV-16 and Anti-HPV-18 Antibodies Anti-HPV-18	2382.3 EL.U/mL Interval 2179.2 to 2604.3	2256.3 EL.U/mL Interval 2070.7 to 2458.7

SECONDARY outcome

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

Population: Analysis was performed on the Total Vaccinated Cohort, on subjects with available data.

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

Outcome measures

Outcome measures
Measure	Cervarix-12 Group n=402 Participants Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=401 Participants Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Solicited Local Symptoms Pain	385 Participants	386 Participants
Number of Subjects Reporting Solicited Local Symptoms Redness	201 Participants	182 Participants
Number of Subjects Reporting Solicited Local Symptoms Swelling	158 Participants	145 Participants

SECONDARY outcome

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

Population: Analysis was performed on the Total Vaccinated Cohort, on subjects with available data.

Solicited general symptoms assessed include arthralgia, fatigue, fever, gastrointestinal symptoms, headache, myalgia, rash, and urticaria.

Outcome measures

Outcome measures
Measure	Cervarix-12 Group n=402 Participants Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=401 Participants Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Solicited General Symptoms Arthralgia	85 Participants	78 Participants
Number of Subjects Reporting Solicited General Symptoms Fatigue	245 Participants	237 Participants
Number of Subjects Reporting Solicited General Symptoms Temperature ≥ 37.5°C	37 Participants	29 Participants
Number of Subjects Reporting Solicited General Symptoms Gastro-intestinal symptoms	85 Participants	86 Participants
Number of Subjects Reporting Solicited General Symptoms Headache	203 Participants	199 Participants
Number of Subjects Reporting Solicited General Symptoms Myalgia	167 Participants	168 Participants
Number of Subjects Reporting Solicited General Symptoms Rash	30 Participants	34 Participants
Number of Subjects Reporting Solicited General Symptoms Urticaria	12 Participants	18 Participants

SECONDARY outcome

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

Population: Analysis was performed on the Total Vaccinated Cohort, on subjects with available data.

An AE is 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.

Outcome measures

Outcome measures
Measure	Cervarix-12 Group n=403 Participants Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=401 Participants Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Unsolicited Adverse Events (AE)	117 Participants	129 Participants

SECONDARY outcome

Timeframe: During the entire study period (up to Month 18 or up to Month 12)

Entire study period = up to Month 18 Cervarix-12 \& Month 12 Cervarix-6. NOCDs assessed include eg. autoimmune disorders (NOADs), asthma, type I diabetes. MSCs assessed include AEs prompting emergency room visits and physician office visits not related to common illnesses. An SAE is any untoward medical occurrence that: results in death, is lifethreatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.

Outcome measures

Outcome measures
Measure	Cervarix-12 Group n=403 Participants Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=401 Participants Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs), New Onset Autoimmune Diseases (NOADs), Serious Adverse Events (SAEs), and Medically Significant Conditions (MSCs) MSCs	42 Participants	44 Participants
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs), New Onset Autoimmune Diseases (NOADs), Serious Adverse Events (SAEs), and Medically Significant Conditions (MSCs) NOCDs	0 Participants	5 Participants
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs), New Onset Autoimmune Diseases (NOADs), Serious Adverse Events (SAEs), and Medically Significant Conditions (MSCs) NOADs	0 Participants	2 Participants
Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs), New Onset Autoimmune Diseases (NOADs), Serious Adverse Events (SAEs), and Medically Significant Conditions (MSCs) SAEs	12 Participants	9 Participants

SECONDARY outcome

Timeframe: During the entire study period (up to Month 18 or Month 12)

Population: Analysis was performed on the Total vaccinated cohort, on pregnant subjects

Entire study period = up to Month 18 Cervarix-12 \& Month 12 Cervarix-6 Number of pregnancies and pregnancy outcomes.

Outcome measures

Outcome measures
Measure	Cervarix-12 Group n=5 Participants Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=3 Participants Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Number of Subjects With Pregnancies and Their Outcomes Elective abortion	0 Participants	2 Participants
Number of Subjects With Pregnancies and Their Outcomes Normal infant	2 Participants	1 Participants
Number of Subjects With Pregnancies and Their Outcomes Abortion threatened	1 Participants	0 Participants
Number of Subjects With Pregnancies and Their Outcomes Ongoing	1 Participants	0 Participants
Number of Subjects With Pregnancies and Their Outcomes Foetal distress syndrome	1 Participants	0 Participants

SECONDARY outcome

Timeframe: After the third vaccine dose

Outcome measures

Outcome measures
Measure	Cervarix-12 Group n=403 Participants Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=401 Participants Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Number of Subjects Completing the 3-dose Vaccination Schedule	388 Participants	397 Participants

Adverse Events

Cervarix-12 Group

Serious events: 12 serious events

Other events: 388 other events

Deaths: 0 deaths

Cervarix-6 Group

Serious events: 9 serious events

Other events: 389 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Cervarix-12 Group n=403 participants at risk Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=401 participants at risk Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
General disorders Pain	95.5% 385/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	96.3% 386/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
General disorders Redness	49.9% 201/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	45.4% 182/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
General disorders Swelling	39.2% 158/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	36.2% 145/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
General disorders Arthralgia	21.1% 85/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	19.5% 78/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
General disorders Fatigue	60.8% 245/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	59.1% 237/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
General disorders Temperature ≥ 37.5°C	9.2% 37/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	7.2% 29/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
General disorders Gastrointestinal symptoms	21.1% 85/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	21.4% 86/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
General disorders Headache	50.4% 203/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	49.6% 199/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
General disorders Myalgia	41.4% 167/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	41.9% 168/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
General disorders Rash	7.4% 30/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	8.5% 34/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.

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

Measure	Cervarix-12 Group n=403 participants at risk Women received 3 doses of Cervarix™ (human papillomavirus \[HPV\] vaccine) administered according to a 0, 1, 12-month schedule.	Cervarix-6 Group n=401 participants at risk Women received 3 doses of Cervarix™ (HPV vaccine) administered according to a 0, 1, 6-month schedule.
Infections and infestations Appendicitis	0.50% 2/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.25% 1/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer female	0.00% 0/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.25% 1/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Musculoskeletal and connective tissue disorders Chondropathy	0.00% 0/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.25% 1/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Gastrointestinal disorders Constipation	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
General disorders Cyst	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Infections and infestations Gastroenteritis	0.00% 0/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.25% 1/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Vascular disorders Hypertension	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Reproductive system and breast disorders Ovarian cyst ruptured	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Infections and infestations Pharyngitis	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.25% 1/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Infections and infestations Sinusitis	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Injury, poisoning and procedural complications Tendon injury	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Endocrine disorders Thyroiditis	0.00% 0/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.25% 1/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Infections and infestations Urinary tract infection	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.25% 1/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Infections and infestations Tracheitis	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Ear and labyrinth disorders Vertigo	0.00% 0/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.25% 1/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Gastrointestinal disorders Abdominal pain	0.50% 2/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Pregnancy, puerperium and perinatal conditions Abortion threatened	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Respiratory, thoracic and mediastinal disorders Brain hypoxia	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Pregnancy, puerperium and perinatal conditions Cephalhaematoma	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Nervous system disorders Convulsion	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Pregnancy, puerperium and perinatal conditions Foetal distress syndrome	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Injury, poisoning and procedural complications Multiple injuries	0.25% 1/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.00% 0/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/403 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.	0.25% 1/401 Analysis for other adverse events were performed on the Total vaccinated cohort, on subjects with available data.