CompletedNCT00345878Updated Jul 20, 2018Results posted

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

A Phase 3 interventional study of Placebo and HPV-16/18 L1 VLP AS04 (Cervarix TM) in Infections, Papillomavirus, sponsored by GlaxoSmithKline. Completed at 2 sites in Malaysia. Open to female participants aged 18 Years to 35 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-07-20.

Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Prevention

Phase: Phase 3
Study type: Interventional
Enrollment: 271
Allocation: Randomized
Ages: 18 Years to 35 Years
Sex: Female

Study summary

Human papillomavirus infection has clearly been recognized as the cause of cervical cancer. The infection of the cervix by certain oncogenic types of HPV, if not cleared, can lead to cervical cancer in women. This study will evaluate the immunogenicity and safety of the HPV-16/18 L1 VLP AS04 vaccine.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Read the detailed description

The protocol was primarily amended for the following reasons:

Merck's tetravalent HPV vaccine, Gardasil®, has been licensed and is now becoming commercially available in an increasing number of countries. Therefore, the study procedures were revised to include questions at every visit to determine if subjects have received an HPV vaccine outside of the study.
It was decided to offer GSK Biologicals' HPV vaccine to all subjects in the control group at the end of the study. The HPV vaccine will be offered to these subjects based on its local indication once the vaccine is marketed in Malaysia.

Conditions studied

Infections, Papillomavirus

Keywords

HPV-16/18 L1 VLP AS04
Cervical neoplasia
Cervical cancer
Human Papillomavirus (HPV)
Double-blind
AS04

In context

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 35 Years
Sexes eligible: Female
Accepts healthy volunteers: Yes

Inclusion criteria

Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
A female from Malaysia between, and including, 18 and 35 years of age at the time of the first vaccination.
Written informed consent obtained from the subject.
Healthy subjects as established by medical history and clinical examination before entering into the study.
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.

Exclusion criteria

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.
Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after the first dose of vaccine. Administration of routine vaccines up to 8 days before the first dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.
previous administration of components of the investigational vaccine
Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
Hypersensitivity to latex.
Acute disease at the time of enrolment.
Known acute or chronic, clinically significant neurologic, pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
History of chronic condition(s) requiring treatment.
Administration of immunoglobulins and/or any blood product within three months preceding the first dose of study vaccine(s) or planned administration during the study period. Enrolment will be deferred until the subject is outside of specified window.
Pregnant or lactating female.
Female planning to become pregnant or planning to discontinue contraceptive precautions.

Study design

Phase: Phase 3
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 271 participants (actual)

Study arms

Experimental
Cervarix Group
Subjects received 3 doses of HPV-16/18 L1 VLP AS04 (Cervarix™) according to a 0, 1, 6-month schedule.
Biological: HPV-16/18 L1 VLP AS04 (Cervarix TM)
Placebo comparator
Placebo Group
Subjects received 3 doses of Placebo according to a 0, 1, 6-month schedule.
Biological: Placebo

Interventions

BiologicalPlacebo
Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
BiologicalHPV-16/18 L1 VLP AS04 (Cervarix TM)
Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.
Also known as: GSK Biologicals' HPV-16/18 VLP/AS04 vaccine

What researchers measure

Primary outcomes

Number of Subjects Who Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
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.
Time frame: At Month 7

Secondary outcomes

Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).
Time frame: At Month 0 and Month 7
Number of Subjects Reporting Solicited Symptoms
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.
Time frame: During the 7 days after each vaccination
Number of Subjects Reporting Unsolicited Adverse Events (AEs)
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.
Time frame: Within 30 days after any vaccination
Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (AEs)
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.
Time frame: Throughout the study period (up to Month 7)
Number of Subjects Reporting Serious Adverse Events
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.
Time frame: Throughout the study period (up to Month 7)

Results

Posted Dec 15, 2009

Participant flow

Participant flow — Overall Study
Milestone	Cervarix Group	Placebo Group
Started	135	136
Completed	131	135
Not completed	4	1
Withdrew: Adverse event	1	0
Withdrew: Lost to follow-up	2	1
Withdrew: Other	1	0

Outcome measures

PrimaryNumber of Subjects Who Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies

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.

Time frame:: At Month 7
Reported as:: Count of participants · 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
Participants	Cervarix Group	Placebo Group
Anti-HPV16	112	4
Anti-HPV18	106	2

SecondaryTiters of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies

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

Time frame:: At Month 0 and Month 7
Reported as:: Geometric mean · EL.U/mL

Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
EL.U/mL	Cervarix Group	Placebo Group
Anti-HPV16 (at Month 0)	5.1 (4.3 to 6.0)	4.6 (4.2 to 5.0)
Anti-HPV16 (at Month 7)	11133.3 (9817.6 to 12625.3)	4.7 (4.2 to 5.3)
Anti-HPV18 (at Month 0)	4.3 (3.9 to 4.7)	4.2 (3.8 to 4.7)
Anti-HPV18 (at Month 7)	4264.2 (3771.6 to 4821.2)	4.2 (3.8 to 4.7)

SecondaryNumber of Subjects Reporting Solicited Symptoms

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.

Time frame:: During the 7 days after each vaccination
Reported as:: Count of participants · Participants

Number of Subjects Reporting Solicited Symptoms
Participants	Cervarix Group	Placebo Group
Pain	121	101
Redness	48	40
Swelling	42	25
Arthralgia	39	26
Fatigue	52	48
Fever (above 37.5 degree Celsius)	19	17
Gastro-intestinal symptoms	18	18
Headache	46	47
Myalgia	48	32
Rash	4	7
Urticaria	4	2

SecondaryNumber of Subjects Reporting Unsolicited Adverse Events (AEs)

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.

Time frame:: Within 30 days after any vaccination
Reported as:: Count of participants · Participants

Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Participants	Cervarix Group	Placebo Group
Number of Subjects Reporting Unsolicited Adverse Events (AEs)	30	36

SecondaryNumber of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (AEs)

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.

Time frame:: Throughout the study period (up to Month 7)
Reported as:: Count of participants · Participants

Number of Subjects Reporting Unsolicited Adverse Events as New Onset Chronic Diseases (NOCDs) and Other Medically Significant Adverse Events (AEs)
Participants	Cervarix Group	Placebo Group
NOCDs	1	0
Medically significant AEs	10	11

SecondaryNumber of Subjects Reporting Serious Adverse Events

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.

Time frame:: Throughout the study period (up to Month 7)
Reported as:: Count of participants · Participants

Number of Subjects Reporting Serious Adverse Events
Participants	Cervarix Group	Placebo Group
Number of Subjects Reporting Serious Adverse Events	3	3

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cervarix Group	—	3/135 (2.2%)	126/135 (93.3%)
Placebo Group	—	3/136 (2.2%)	114/136 (83.8%)

Most frequent serious events

Most frequent serious events
Event	Cervarix Group	Placebo Group
Dengue feverInfections and infestations	1/135	1/136
Abortion missedPregnancy, puerperium and perinatal conditions	1/135	0/136
CholelithiasisHepatobiliary disorders	1/135	0/136
Chronic tonsillitisInfections and infestations	1/135	0/136
Nasal turbinate hypertrophyRespiratory, thoracic and mediastinal disorders	1/135	0/136
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders	0/135	1/136
OverdoseInjury, poisoning and procedural complications	0/135	1/136

Most frequent other events

Showing 10 of 12

Most frequent other events
Event	Cervarix Group	Placebo Group
PainGeneral disorders	121/135	101/136
FatigueGeneral disorders	52/135	48/136
RednessGeneral disorders	48/135	40/136
MyalgiaGeneral disorders	48/135	32/136
HeadacheGeneral disorders	46/135	47/136
SwellingGeneral disorders	42/135	25/136
ArthralgiaGeneral disorders	39/135	26/136
Fever (above 37.5 degree Celsius)General disorders	19/135	17/136
Gastro-intestinal symptomsGeneral disorders	18/135	18/136
Upper respiratory tract infectionInfections and infestations	8/135	10/136

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	Cervarix Group	Placebo Group	Total
Mean	24.8 ± 3.91	25.0 ± 4.14	24.9 ± 4.02

Sex: Female, Male
Sex: Female, Male(Participants)	Cervarix Group	Placebo Group	Total
Female	135	136	271
Male	0	0	0

Study locations

2 sites

GSK Investigational Site
Kerajaan Persekutuan Putrajaya, 62250, Malaysia
GSK Investigational Site
Kuala Lumpur, 50603, Malaysia

References and documents

Publications

Verstraeten T, Descamps D, David MP, Zahaf T, Hardt K, Izurieta P, Dubin G, Breuer T. Analysis of adverse events of potential autoimmune aetiology in a large integrated safety database of AS04 adjuvanted vaccines. Vaccine. 2008 Dec 2;26(51):6630-8. doi: 10.1016/j.vaccine.2008.09.049. PubMed 18845199 ↗

Individual participant data

Plan to share: Yes — Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 20, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00345878
Lead sponsor: GlaxoSmithKline
Responsible party: Sponsor
First posted: Jun 29, 2006
Start date: Sep 25, 2006
Primary completion: Dec 21, 2007
Completion: Dec 21, 2007
Results posted: Dec 15, 2009
Last update: Jul 20, 2018

Study contacts

GSK Clinical Trials

study director · GlaxoSmithKline

View the source record on ClinicalTrials.gov ↗

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