Clinical trial NCT00316693: Human Papillomavirus (HPV) Vaccine (Cervarix TM) Efficacy, Immunogenicity & Safety Trial in Adult Japanese Women With GSK Biologicals HPV-16/18 Vaccine
Official title: A Phase II Study to Assess the Efficacy, Immunogenicity and Safety of GSK Biologicals' HPV-16/18 L1 VLP AS04 (Cervarix TM) Vaccine Administered Intramuscularly According to a 0, 1, 6 Month Schedule in Healthy Japanese Female Subjects Aged 20 - 25 Years.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infections, Papillomavirus
Keywords: HPV Vaccine Efficacy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-04-21
Enrollment: 1046
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 25
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. Indeed, certain oncogenic types of HPV can infect the cervix (part of the uterus or womb). This infection may go away by itself, but if it does not go away (this is called persistent infection), it can lead in women over a long period of time to cancer of the cervix. This study will evaluate the efficacy in prevention of persistent HPV-16 or HPV-18 cervical infection lasting at least 6 months, the immunogenicity and safety of GSK Biologicals HPV-16/18 vaccine (Cervarix TM ) over 24 months in Japanese adult women aged 20 - 25 years of age at study start. Approximately 1000 study subjects will either receive the HPV vaccine or a control vaccine (Hepatitis A vaccine) administered intramuscularly according to a 0-1-6 month schedule.

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

Detailed description: The Protocol Posting has been updated to reflect changes as a consequence of an amendment to the protocol. Sections impacted are Official Title of the study and Intervention name.

Eligibility criteria: Inclusion criteria :

* Subjects who the investigator/co-investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
* A Japanese female subject between, and including, 20 and 25 years of age at the time of the first vaccination.
* Written informed consent obtained from the subject prior to enrolment.
* Healthy subjects as established by medical history and history-oriented clinical examination before entering into the study.
* Subjects must have a negative urine pregnancy test.
* Subjects must be of non-childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series.
* Subject must have an intact cervix

Exclusion criteria:

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine/control within 30 days preceding the first dose of study vaccine/control, or planned use during the study period.
* Pregnant or breastfeeding women. Women must be at least 3 months post-pregnancy and not breastfeeding to enter the study.
* A women planning to become pregnant, likely to become pregnant or planning to discontinue contraceptive precautions during the study period, up to 2 months after the last vaccine dose
* previous administration of components of the investigational vaccine
* Chronic administration 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. Routine vaccines may be allowed up to 8 days before the first dose of study vaccine.
* Previous vaccination against HPV.
* History of vaccination against hepatitis A or a known clinical history of hepatitis A disease
* Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine or planned administration 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 study vaccines
* Hypersensitivity to latex
* Known acute or chronic, clinically significant pulmonary, cardiovascular, neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests.
* Cancer or autoimmune disease under treatment.
* History of having had colposcopy or has planned a colposcopy to evaluate an abnormal cervical cytology (Pap smear) test.
* Heavy bleeding or heavy vaginal discharge such that a pelvic examination can not be performed
* Acute disease at the time of enrolment.
* Oral temperature \>= 37.5°C / axillary temperature \> 37.5°C.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).

Primary outcomes:
measure: Number of Subjects With Persistent Cervical Infection With Human Papillomavirus 16 (HPV-16) or Human Papillomavirus 18 (HPV-18)
timeFrame: Throughout the study period (up to Month 24)
Secondary outcomes:
measure: Number of Subjects With Incident Cervical Infection With Human Papillomavirus 16 (HPV-16) or Human Papillomavirus 18 (HPV-18)
timeFrame: Up to Month 24
measure: Number of Subjects With Cytologically-confirmed Abnormalities Concurrently Associated With Human Papillomavirus 16 (HPV-16) and/or Human Papillomavirus 18 (HPV-18) Cervical Infection
timeFrame: Up to Month 24
measure: Number of Subjects With Histopathologically-confirmed Lesions Concurrently Associated With Human Papillomavirus 16 (HPV-16) and/or Human Papillomavirus (HPV-18) Cervical Infection
timeFrame: Up to Month 24
measure: Number of Subjects With Incident Cervical Infection With Any Oncogenic Human Papillomavirus (HPV) Types
timeFrame: Up to Month 24
measure: Number of Subjects With Persistent Cervical Infection With Any Oncogenic Human Papillomavirus (HPV) Types
timeFrame: Up to Month 24
measure: Number of Subjects With Cytologically-confirmed Abnormalities Concurrently Associated With Cervical Infection With Any Oncogenic Human Papillomavirus (HPV) Type
timeFrame: Up to Month 24
measure: Number of Subjects With Histopathologically Confirmed Lesions Concurrently Associated With Cervical Infection With Any Oncogenic Human Papillomavirus (HPV) Type
timeFrame: Up to Month 24
measure: Number of Subjects With Anti-human Papillomavirus 16 and 18 (Anti-HPV-16 and Anti-HPV-18) Antibody Titers Above the Cut-off Value
timeFrame: At Months 0 (pre-vaccination), 6, 7, 12, 18 and 24
measure: Titers of Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies
timeFrame: At Months 0, 6, 7, 12, 18 and 24
measure: Number of Subjects Reporting Solicited Local and General Symptoms
timeFrame: Within 7 days after each and any vaccination
measure: Number of Subjects Reporting Unsolicited Adverse Events (AE)
timeFrame: Within 30 days after any vaccination
measure: Number of Subjects Reporting Serious Adverse Events (SAE)
timeFrame: Throughout the study period (up to Month 24)
measure: Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) and Other Medically Significant Conditions (MSCs)
timeFrame: Throughout the study period (up to Month 24)
measure: Outcome of Any Reported Pregnancies
timeFrame: Throughout the study period (up to Month 24)
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Hematological Parameters
timeFrame: At Month 0 and Month 7
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical Parameters
timeFrame: At Month 0 and Month 7
measure: Number of Subjects Reporting Abnormal Biochemical Parameters in Urine Samples
timeFrame: At Month 0 and Month 7
Other outcomes:
Locations:
city: Kagoshima
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Konno R, Dobbelaere KO, Godeaux OO, Tamura S, Yoshikawa H. Immunogenicity, reactogenicity, and safety of human papillomavirus 16/18 AS04-adjuvanted vaccine in Japanese women: interim analysis of a phase II, double-blind, randomized controlled trial at month 7. Int J Gynecol Cancer. 2009 Jul;19(5):905-11. doi: 10.1111/IGC.0b013e3181a23c0e.
citation: Konno R, Tamura S, Dobbelaere K, Yoshikawa H. Efficacy of human papillomavirus 16/18 AS04-adjuvanted vaccine in Japanese women aged 20 to 25 years: interim analysis of a phase 2 double-blind, randomized, controlled trial. Int J Gynecol Cancer. 2010 Apr;20(3):404-10. doi: 10.1111/IGC.0b013e3181d373a5.
citation: Konno R, Tamura S, Dobbelaere K, Yoshikawa H. Prevalence and type distribution of human papillomavirus in healthy Japanese women aged 20 to 25 years old enrolled in a clinical study. Cancer Sci. 2011 Apr;102(4):877-82. doi: 10.1111/j.1349-7006.2011.01878.x. Epub 2011 Feb 17.
citation: Konno R et al. Efficacy, immunogenicity and safety of HPV 16/18 AS04-adjuvanted vaccine in Japanese women. Abstract presented at European Research Organization on Genital Infection and Neoplasia 2010 (EUROGIN). Monte Carlo, Monaco, 17-20 February 2010.
citation: Konno R et al. Interim analysis of clinical trial of HPV-16/18-AS04 vaccine in Japan. Abstract presented at the 25th International Papillomavirus Conference, Malmö, Sweden, 8-14 May 2009.
citation: 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.
citation: Chen J, Gopala K, Akarsh PK, Struyf F, Rosillon D. Prevalence and Incidence of Human Papillomavirus (HPV) Infection Before and After Pregnancy: Pooled Analysis of the Control Arms of Efficacy Trials of HPV-16/18 AS04-Adjuvanted Vaccine. Open Forum Infect Dis. 2019 Dec 4;6(12):ofz486. doi: 10.1093/ofid/ofz486. eCollection 2019 Dec.
citation: Konno R, Yoshikawa H, Okutani M, Quint W, V Suryakiran P, Lin L, Struyf F. Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical intraepithelial neoplasia and cervical infection in young Japanese women. Hum Vaccin Immunother. 2014;10(7):1781-94. doi: 10.4161/hv.28712.
citation: Konno R, Tamura S, Dobbelaere K, Yoshikawa H. Efficacy of human papillomavirus type 16/18 AS04-adjuvanted vaccine in Japanese women aged 20 to 25 years: final analysis of a phase 2 double-blind, randomized controlled trial. Int J Gynecol Cancer. 2010 Jul;20(5):847-55. doi: 10.1111/IGC.0b013e3181da2128.