Trial Outcomes & Findings for Study to Evaluate the Immune Response and Safety of GSK Biologicals' HPV Vaccine in Healthy Women Aged 18-35 Years (NCT NCT00345878)

Last Updated: 2018-07-20

Results Overview

Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subjects seronegative before vaccination. Cut-off values assessed include 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

271 participants

Primary outcome timeframe

At Month 7

Results posted on

2018-07-20

Participant Flow

Participant milestones

Participant milestones
Measure	Cervarix Group Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.	Placebo Group Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.
Overall Study STARTED	135	136
Overall Study COMPLETED	131	135
Overall Study NOT COMPLETED	4	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Cervarix Group Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.	Placebo Group Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.
Overall Study Adverse Event	1	0
Overall Study Lost to Follow-up	2	1
Overall Study Other	1	0

Baseline Characteristics

Study to Evaluate the Immune Response and Safety of GSK Biologicals' HPV Vaccine in Healthy Women Aged 18-35 Years

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cervarix Group n=135 Participants Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.	Placebo Group n=136 Participants Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.	Total n=271 Participants Total of all reporting groups
Age, Continuous	24.8 Years STANDARD_DEVIATION 3.91 • n=5 Participants	25.0 Years STANDARD_DEVIATION 4.14 • n=7 Participants	24.9 Years STANDARD_DEVIATION 4.02 • n=5 Participants
Sex: Female, Male Female	135 Participants n=5 Participants	136 Participants n=7 Participants	271 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: At Month 7

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity.

Outcome measures

Outcome measures
Measure	Cervarix Group n=112 Participants Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.	Placebo Group n=115 Participants Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.
Number of Subjects Who Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies Anti-HPV16	112 Participants	4 Participants
Number of Subjects Who Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies Anti-HPV18	106 Participants	2 Participants

SECONDARY outcome

Timeframe: At Month 0 and Month 7

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity.

Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).

Outcome measures

Outcome measures
Measure	Cervarix Group n=126 Participants Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.	Placebo Group n=129 Participants Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.
Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies Anti-HPV16 (at Month 0)	5.1 EL.U/mL Interval 4.3 to 6.0	4.6 EL.U/mL Interval 4.2 to 5.0
Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies Anti-HPV16 (at Month 7)	11133.3 EL.U/mL Interval 9817.6 to 12625.3	4.7 EL.U/mL Interval 4.2 to 5.3
Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies Anti-HPV18 (at Month 0)	4.3 EL.U/mL Interval 3.9 to 4.7	4.2 EL.U/mL Interval 3.8 to 4.7
Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies Anti-HPV18 (at Month 7)	4264.2 EL.U/mL Interval 3771.6 to 4821.2	4.2 EL.U/mL Interval 3.8 to 4.7

SECONDARY outcome

Timeframe: During the 7 days after each vaccination

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

Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include arthralgia, fatigue, fever, gastro-intestinal symptoms, headache, myalgia, rash and urticaria.

Outcome measures

Outcome measures
Measure	Cervarix Group n=132 Participants Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.	Placebo Group n=135 Participants Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Solicited Symptoms Pain	121 Participants	101 Participants
Number of Subjects Reporting Solicited Symptoms Redness	48 Participants	40 Participants
Number of Subjects Reporting Solicited Symptoms Swelling	42 Participants	25 Participants
Number of Subjects Reporting Solicited Symptoms Arthralgia	39 Participants	26 Participants
Number of Subjects Reporting Solicited Symptoms Fatigue	52 Participants	48 Participants
Number of Subjects Reporting Solicited Symptoms Fever (above 37.5 degree Celsius)	19 Participants	17 Participants
Number of Subjects Reporting Solicited Symptoms Gastro-intestinal symptoms	18 Participants	18 Participants
Number of Subjects Reporting Solicited Symptoms Headache	46 Participants	47 Participants
Number of Subjects Reporting Solicited Symptoms Myalgia	48 Participants	32 Participants
Number of Subjects Reporting Solicited Symptoms Rash	4 Participants	7 Participants
Number of Subjects Reporting Solicited Symptoms Urticaria	4 Participants	2 Participants

SECONDARY outcome

Timeframe: Within 30 days after any vaccination

Unsolicited adverse event = Any adverse event (AE) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.

Outcome measures

Outcome measures
Measure	Cervarix Group n=135 Participants Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.	Placebo Group n=136 Participants Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Unsolicited Adverse Events (AEs)	30 Participants	36 Participants

SECONDARY outcome

Timeframe: Throughout the study period (up to Month 7)

NOCDs assessed include e.g. autoimmune disorders, asthma, type I diabetes, allergies,... Medically significant AEs assessed include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or SAEs that are not related to common diseases.

Outcome measures

Outcome measures
Measure	Cervarix Group n=135 Participants Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.	Placebo Group n=136 Participants Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (AEs) NOCDs	1 Participants	0 Participants
Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (AEs) Medically significant AEs	10 Participants	11 Participants

SECONDARY outcome

Timeframe: Throughout the study period (up to Month 7)

Serious adverse events assessed include medical occurrences that results in death, is 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.

Outcome measures

Outcome measures
Measure	Cervarix Group n=135 Participants Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.	Placebo Group n=136 Participants Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.
Number of Subjects Reporting Serious Adverse Events	3 Participants	3 Participants

Adverse Events

Cervarix Group

Serious events: 3 serious events

Other events: 126 other events

Deaths: 0 deaths

Placebo Group

Serious events: 3 serious events

Other events: 114 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cervarix Group n=135 participants at risk Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.	Placebo Group n=136 participants at risk Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.
Infections and infestations Dengue fever	0.74% 1/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	0.74% 1/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
Pregnancy, puerperium and perinatal conditions Abortion missed	0.74% 1/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	0.00% 0/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
Hepatobiliary disorders Cholelithiasis	0.74% 1/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	0.00% 0/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
Infections and infestations Chronic tonsillitis	0.74% 1/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	0.00% 0/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	0.74% 1/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
Respiratory, thoracic and mediastinal disorders Nasal turbinate hypertrophy	0.74% 1/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	0.00% 0/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
Injury, poisoning and procedural complications Overdose	0.00% 0/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	0.74% 1/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.

Other adverse events

Other adverse events
Measure	Cervarix Group n=135 participants at risk Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.	Placebo Group n=136 participants at risk Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.
General disorders Pain	89.6% 121/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	74.3% 101/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
General disorders Redness	35.6% 48/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	29.4% 40/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
General disorders Swelling	31.1% 42/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	18.4% 25/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
General disorders Arthralgia	28.9% 39/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	19.1% 26/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
General disorders Fatigue	38.5% 52/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	35.3% 48/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
General disorders Fever (above 37.5 degree Celsius)	14.1% 19/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	12.5% 17/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
General disorders Gastro-intestinal symptoms	13.3% 18/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	13.2% 18/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
General disorders Headache	34.1% 46/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	34.6% 47/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
General disorders Myalgia	35.6% 48/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	23.5% 32/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
General disorders Rash	3.0% 4/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	5.1% 7/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
Infections and infestations Upper respiratory tract infection	5.9% 8/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	7.4% 10/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.
Infections and infestations Influenza	2.2% 3/135 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.	5.9% 8/136 Events collected by systematic assessment are reported for subjects with a symptom diary card available. Events collected by a non-systematic method are reported for the Total Vaccinated cohort.

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