Efficacy Study of HPV-16/18 Vaccine (GSK 580299) to Prevent HPV-16 and/or -18 Cervical Infection in Young Healthy Women
Primary Purpose
Infections, Papillomavirus
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Cervarix
placebo
Sponsored by

About this trial
This is an interventional prevention trial for Infections, Papillomavirus focused on measuring HPV, vaccine
Eligibility Criteria
Inclusion Criteria:
- Female between and including 15 and 25 years of age at the time of screening (must not have reached 26th birthday)
- Written informed consent obtained from the subject prior to enrolment (for subjects below the legal age of consent, written informed consent must also be obtained from a parent or legal guardian of the subject)
- Free of obvious health problems, as established by medical history and a directed physical examination
- No more than 6 lifetime sexual partners prior to enrolment
- Intact uterus
- Subject must be of non-childbearing potential, i.e., either surgically sterilised or, if of childbearing potential, she must be abstinent or must be using an effective method of birth control for 30 days prior to vaccination, have a negative urine pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series
- For subjects not enrolled in the HPV epidemiology study (999910/106) and for subjects completing the study (999910/106) >90 days prior to enrolment in the present study: agreement to complete both entrance and exit study questionnaires concerning general personal information, and sexual, contraceptive, reproductive and other gynaecological medical history
- For subjects previously enrolled in the HPV epidemiology study (and who completed the study and an entrance questionnaire) ≤ 90 days prior to enrolment in the present study: agreement to complete the exit questionnaire only.
- Normal cervical cytology (Pap smear) at screening, using the Cytyc ThinPrep® Pap Test. A normal Pap smear must also be adequate for interpretation, including the presence of endocervical cells; a Pap smear that is normal but inadequate for interpretation must be repeated as part of the protocol
- Seronegative for HPV-16 and HPV-18 antibody by ELISA at screening
- HPV DNA PCR negative for high-risk HPV types by PCR at screening. Genotyping will be specified using a reverse line probe assay specific for the detection of high-risk HPV types such as HPV-16, HPV-18 and HPV-16/18-related phylogenetic types
Exclusion Criteria:
- Pregnant or lactating female
- Female planning to become pregnant during the first eight months of the study (months 0-8)
- Abnormal vaginal discharge at the time of entry (once these subjects have received therapy to eradicate any discharge they will be eligible to participate in study)
- Previous administration of any components of the investigational vaccine
- Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
- Administration of immunoglobulin and/or any blood products within the three months (90 days) preceding the first dose of study vaccine or planned administration during the study period
- Planned administration / administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine. Administration of routine Meningococcal, Hepatitis A, Hepatitis B, Influenza, and Diphtheria/Tetanus vaccine up to 8 days before the first dose of study vaccine is allowed
- Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period
- Receiving or expecting therapy for external or internal condylomata. Subjects with external condylomata not requiring therapy are eligible to participate in the study
- Genital herpes disease involving the cervix or characterized (on examination or by history) by extensive external lesions. Subjects with a history of recurrent genital herpes disease characterized by limited external lesions are eligible to participate in the study
- History of an abnormal cervical cytology (Pap smear) test (other than a single prior report of ASCUS with a subsequent normal report)
- Treatment for cervical disease by ablative therapy (cryotherapy or laser ablation) or excisional therapy (laser cone biopsy, loop excision, cold-knife conization)
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
- A family history of congenital or hereditary immunodeficiency
- Major congenital defects or serious chronic illness
- History of any neurologic disorders or seizures, with the exception of a single febrile seizure during childhood
- Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests
- Acute disease at the time of enrolment.
- Oral temperature ≥99.5°F (≥37.5°C) / axillary temperature ≥99.5°F (37.5°C) / rectal temperature ≥100.4°F (≥38.0°C) / tympanic temperature on oral setting ≥99.5°F (37.5°C) / tympanic temperature on rectal setting ≥100.4°F (≥38.0°C)
- History of chronic alcohol consumption and/or intravenous drug abuse within the past 2 years
- Known or suspected allergy to any vaccine component
- Hepatomegaly, right upper quadrant abdominal pain or tenderness
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
A
B
Arm Description
Outcomes
Primary Outcome Measures
Cervical infection with HPV-16 and/or HPV-18
Secondary Outcome Measures
Persistent cervical infection with HPV-16 and/or HPV-18
Cytologically confirmed or histopathologically confirmed LSIL, HSIL, squamous cell cancer, or adenocarcinoma concurrently associated with HPV-16 and/or HPV-18 cervical infection
Determination of viral load for HPV-16 and HPV-18 (by PCR) for both self-obtained and Pap smear cervical samples
Cervical infection with HPV-16, HPV-18 and/or HPV-16/18-related phylogenetic types
Persistent cervical infection with HPV-16, HPV-18 and/or HPV-16/18-related phylogenetic types
Cytologically confirmed or histopathologically confirmed LSIL, HSIL, squamous cell cancer, adenocarcinoma concurrently associated with cervical infection with HPV-16; HPV-18 and/or HPV-16/18-related phylogenetic types.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00689741
Brief Title
Efficacy Study of HPV-16/18 Vaccine (GSK 580299) to Prevent HPV-16 and/or -18 Cervical Infection in Young Healthy Women
Official Title
A Double-blind, Placebo-controlled, Randomised Study of the Efficacy of an HPV-16/18 VLP Vaccine in the Prevention of HPV-16 and/or HPV-18 Cervical Infection in Healthy Adolescent and Young Adult Women in North America and Brazil.
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
January 2001 (undefined)
Primary Completion Date
April 2003 (Actual)
Study Completion Date
April 2003 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this phase IIB MedImmune-sponsored study was to evaluate the efficacy of the HPV-16/18 VLP vaccine in the prevention of infection with HPV-16 and/or HPV-18 in adolescent and young adult women. A vaccine that prevents, or even reduces, the incidence of the common types of high-risk HPVs, particularly HPV-16 and HPV-18, could result in significant reduction in the incidence of cervical cancer and cancer-related mortality, as well as a reduction in the incidence of surgical procedures following abnormal Pap smears.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infections, Papillomavirus
Keywords
HPV, vaccine
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1113 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Experimental
Arm Title
B
Arm Type
Placebo Comparator
Intervention Type
Biological
Intervention Name(s)
Cervarix
Intervention Description
3 doses of IM injection
Intervention Type
Biological
Intervention Name(s)
placebo
Other Intervention Name(s)
Cervarix
Intervention Description
3 doses of IM injection of Al(OH)3 placebo
Primary Outcome Measure Information:
Title
Cervical infection with HPV-16 and/or HPV-18
Time Frame
Throughout the study
Secondary Outcome Measure Information:
Title
Persistent cervical infection with HPV-16 and/or HPV-18
Time Frame
Throughout the study
Title
Cytologically confirmed or histopathologically confirmed LSIL, HSIL, squamous cell cancer, or adenocarcinoma concurrently associated with HPV-16 and/or HPV-18 cervical infection
Time Frame
Throughout the study
Title
Determination of viral load for HPV-16 and HPV-18 (by PCR) for both self-obtained and Pap smear cervical samples
Time Frame
Throughout the study
Title
Cervical infection with HPV-16, HPV-18 and/or HPV-16/18-related phylogenetic types
Time Frame
Throughout the study
Title
Persistent cervical infection with HPV-16, HPV-18 and/or HPV-16/18-related phylogenetic types
Time Frame
Throughout the study
Title
Cytologically confirmed or histopathologically confirmed LSIL, HSIL, squamous cell cancer, adenocarcinoma concurrently associated with cervical infection with HPV-16; HPV-18 and/or HPV-16/18-related phylogenetic types.
Time Frame
Throughout the study
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Female between and including 15 and 25 years of age at the time of screening (must not have reached 26th birthday)
Written informed consent obtained from the subject prior to enrolment (for subjects below the legal age of consent, written informed consent must also be obtained from a parent or legal guardian of the subject)
Free of obvious health problems, as established by medical history and a directed physical examination
No more than 6 lifetime sexual partners prior to enrolment
Intact uterus
Subject must be of non-childbearing potential, i.e., either surgically sterilised or, if of childbearing potential, she must be abstinent or must be using an effective method of birth control for 30 days prior to vaccination, have a negative urine pregnancy test and must agree to continue such precautions for two months after completion of the vaccination series
For subjects not enrolled in the HPV epidemiology study (999910/106) and for subjects completing the study (999910/106) >90 days prior to enrolment in the present study: agreement to complete both entrance and exit study questionnaires concerning general personal information, and sexual, contraceptive, reproductive and other gynaecological medical history
For subjects previously enrolled in the HPV epidemiology study (and who completed the study and an entrance questionnaire) ≤ 90 days prior to enrolment in the present study: agreement to complete the exit questionnaire only.
Normal cervical cytology (Pap smear) at screening, using the Cytyc ThinPrep® Pap Test. A normal Pap smear must also be adequate for interpretation, including the presence of endocervical cells; a Pap smear that is normal but inadequate for interpretation must be repeated as part of the protocol
Seronegative for HPV-16 and HPV-18 antibody by ELISA at screening
HPV DNA PCR negative for high-risk HPV types by PCR at screening. Genotyping will be specified using a reverse line probe assay specific for the detection of high-risk HPV types such as HPV-16, HPV-18 and HPV-16/18-related phylogenetic types
Exclusion Criteria:
Pregnant or lactating female
Female planning to become pregnant during the first eight months of the study (months 0-8)
Abnormal vaginal discharge at the time of entry (once these subjects have received therapy to eradicate any discharge they will be eligible to participate in study)
Previous administration of any components of the investigational vaccine
Chronic administration (defined as more than 14 days) of immuno-suppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
Administration of immunoglobulin and/or any blood products within the three months (90 days) preceding the first dose of study vaccine or planned administration during the study period
Planned administration / administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of study vaccine. Administration of routine Meningococcal, Hepatitis A, Hepatitis B, Influenza, and Diphtheria/Tetanus vaccine up to 8 days before the first dose of study vaccine is allowed
Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period
Receiving or expecting therapy for external or internal condylomata. Subjects with external condylomata not requiring therapy are eligible to participate in the study
Genital herpes disease involving the cervix or characterized (on examination or by history) by extensive external lesions. Subjects with a history of recurrent genital herpes disease characterized by limited external lesions are eligible to participate in the study
History of an abnormal cervical cytology (Pap smear) test (other than a single prior report of ASCUS with a subsequent normal report)
Treatment for cervical disease by ablative therapy (cryotherapy or laser ablation) or excisional therapy (laser cone biopsy, loop excision, cold-knife conization)
Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
A family history of congenital or hereditary immunodeficiency
Major congenital defects or serious chronic illness
History of any neurologic disorders or seizures, with the exception of a single febrile seizure during childhood
Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests
Acute disease at the time of enrolment.
Oral temperature ≥99.5°F (≥37.5°C) / axillary temperature ≥99.5°F (37.5°C) / rectal temperature ≥100.4°F (≥38.0°C) / tympanic temperature on oral setting ≥99.5°F (37.5°C) / tympanic temperature on rectal setting ≥100.4°F (≥38.0°C)
History of chronic alcohol consumption and/or intravenous drug abuse within the past 2 years
Known or suspected allergy to any vaccine component
Hepatomegaly, right upper quadrant abdominal pain or tenderness
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Citations:
PubMed Identifier
19217149
Citation
David MP, Van Herck K, Hardt K, Tibaldi F, Dubin G, Descamps D, Van Damme P. Long-term persistence of anti-HPV-16 and -18 antibodies induced by vaccination with the AS04-adjuvanted cervical cancer vaccine: modeling of sustained antibody responses. Gynecol Oncol. 2009 Dec;115(3 Suppl):S1-6. doi: 10.1016/j.ygyno.2009.01.011. Epub 2009 Feb 12.
Results Reference
background
Citation
David MP et al. Long-term persistence of detectable anti-HPV-16 and anti-HPV-18 antibodies induced by CervarixTM: modelling of sustained antibody responses. Abstract presented at the 26th Annual Meeting of the ESPID. Graz, Austria, 13-17 May 2008.
Results Reference
background
Citation
David M-P et al. Modeling of long-term persistence of anti-HPV-16 and anti-HPV-18 antibodies induced by an AS04-adjuvanted cervical cancer vaccine. Abstract presented at the European Research Organization on Genital Infection and Neoplasia (EUROGIN) International Multidisciplinary Conference. Nice, France, 12-15 November 2008.
Results Reference
background
PubMed Identifier
19221517
Citation
Descamps D, Hardt K, Spiessens B, Izurieta P, Verstraeten T, Breuer T, Dubin G. Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Hum Vaccin. 2009 May;5(5):332-40. doi: 10.4161/hv.5.5.7211. Epub 2009 May 20.
Results Reference
background
Citation
Descamps D et al. Safety of human papillomavirus (HPV)-16/18 AS04 adjuvanted vaccine for cervical cancer prevention: integrated summary of 11 clinical trials. Abstract presented at the 26th Annual Meeting of the ESPID. Graz, Austria, 13-17 May 2008.
Results Reference
background
PubMed Identifier
15541448
Citation
Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, Zahaf T, Innis B, Naud P, De Carvalho NS, Roteli-Martins CM, Teixeira J, Blatter MM, Korn AP, Quint W, Dubin G; GlaxoSmithKline HPV Vaccine Study Group. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet. 2004 Nov 13-19;364(9447):1757-65. doi: 10.1016/S0140-6736(04)17398-4.
Results Reference
background
Citation
Rombo L et al. Tolerability of HPV-16/18 AS04-adjuvanted cervical cancer vaccine. Abstract presented at the European Research Organization on Genital Infection and Neoplasia (EUROGIN) International Multidisciplinary Conference. Nice, France, 12-15 November 2008.
Results Reference
background
PubMed Identifier
18845199
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.
Results Reference
background
PubMed Identifier
31464859
Citation
El-Zein M, Ramanakumar AV, Naud P, Roteli-Martins CM, de Carvalho NS, Colares de Borba P, Teixeira JC, Moscicki AB, Harper DM, Tyring SK, Ramjattan B, Dubin G, Franco EL; HPV-007 Study Group. Determinants of Acquisition and Clearance of Human Papillomavirus Infection in Previously Unexposed Young Women. Sex Transm Dis. 2019 Oct;46(10):663-669. doi: 10.1097/OLQ.0000000000001053.
Results Reference
derived
PubMed Identifier
27566633
Citation
Ramanakumar AV, Naud P, Roteli-Martins CM, de Carvalho NS, de Borba PC, Teixeira JC, Blatter M, Moscicki AB, Harper DM, Romanowski B, Tyring SK, Ramjattan B, Schuind A, Dubin G, Franco EL; HPV-007 Study Group. Incidence and duration of type-specific human papillomavirus infection in high-risk HPV-naive women: results from the control arm of a phase II HPV-16/18 vaccine trial. BMJ Open. 2016 Aug 26;6(8):e011371. doi: 10.1136/bmjopen-2016-011371. Erratum In: BMJ Open. 2016 Sep 02;6(9):e011371corr1.
Results Reference
derived
PubMed Identifier
25424918
Citation
Naud PS, Roteli-Martins CM, De Carvalho NS, Teixeira JC, de Borba PC, Sanchez N, Zahaf T, Catteau G, Geeraerts B, Descamps D. Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: final analysis of a long-term follow-up study up to 9.4 years post-vaccination. Hum Vaccin Immunother. 2014;10(8):2147-62. doi: 10.4161/hv.29532.
Results Reference
derived
PubMed Identifier
24138429
Citation
Aregay M, Shkedy Z, Molenberghs G, David MP, Tibaldi F. Model-based estimates of long-term persistence of induced HPV antibodies: a flexible subject-specific approach. J Biopharm Stat. 2013;23(6):1228-48. doi: 10.1080/10543406.2013.834917.
Results Reference
derived
PubMed Identifier
23063422
Citation
Moscicki AB, Wheeler CM, Romanowski B, Hedrick J, Gall S, Ferris D, Poncelet S, Zahaf T, Moris P, Geeraerts B, Descamps D, Schuind A. Immune responses elicited by a fourth dose of the HPV-16/18 AS04-adjuvanted vaccine in previously vaccinated adult women. Vaccine. 2012 Dec 17;31(1):234-41. doi: 10.1016/j.vaccine.2012.09.037. Epub 2012 Oct 11.
Results Reference
derived
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
580299/001
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
580299/001
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
580299/001
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
580299/001
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
580299/001
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
580299/001
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Learn more about this trial
Efficacy Study of HPV-16/18 Vaccine (GSK 580299) to Prevent HPV-16 and/or -18 Cervical Infection in Young Healthy Women
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