Clinical trial NCT00541970: Partially Blind Study to Evaluate Immunogenicity & Safety of GSK Bio's HPV Vaccine 580299 in Healthy Women Aged 9-25 Yrs
Official title: Evaluation of the Safety and Immunogenicity of GSK Biologicals' HPV Vaccine 580299 When Administered in Healthy Females Aged 9 - 25 Years Using an Alternative Schedule and an Alternative Dosing as Compared to the Standard Schedule and Dosing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Infections, Papillomavirus
Keywords: viral infections
Human Papillomavirus (HPV) vaccine
safety
vaccine
immunogenicity
cervical cancer
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-10-10
Enrollment: 961
Sex: FEMALE
Minimum age (years): 9
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Human Papillomavirus (HPV) infection has been established as a necessary cause of cervical cancer. GlaxoSmithKline (GSK) Biologicals has developed an HPV vaccine (580299) which targets the 2 most common oncogenic HPV types (HPV-16 and HPV-18), found in approximately 70% of all cervical cancers. In previous trials this vaccine has been found to be efficacious in the prevention of incident and persistent HPV-16/18 infections and associated cytological abnormalities and cervical dysplasia. In this partially-blind study, GSK Biologicals will evaluate the safety and immunogenicity of the HPV vaccine using an alternative schedule and an alternative dosing when administered in healthy young females aged 9 to 25 years, as compared to the standard HPV vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. The protocol posting has been updated following a protocol amendment.


Eligibility criteria: Inclusion Criteria:

* Subjects who the investigator believes that they and/or their parents can and will comply with the requirements of the protocol should be enrolled in the study.
* A female subject between, and including, 9 and 25 years of age at the time of the first vaccination.
* Written informed consent/assent obtained from the subject prior to enrolment. For subjects above the legal age of consent, written informed consent must be obtained from the subject. For subjects below the legal age of consent, written informed consent from the subject's parents/legally acceptable representative, and written informed assent must be obtained from the subject.
* Healthy subjects as established by medical history and history-oriented clinical examination before entering into the study.
* Subject must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for two months after completion of the vaccination series.

Exclusion Criteria:

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 24).
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
* Concurrently participating in another clinical study, at any time during the study period (up to Month 24), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
* 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. Planned administration/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.
* Pregnant or breastfeeding female.
* A woman planning to become pregnant or planning to discontinue contraceptive precautions during the study period, up to two months after the last vaccine dose.
* Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period (up to Month 24).
* Previous administration of components of the investigational vaccine.
* Cancer or autoimmune disease under treatment.
* Any medically diagnosed 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.
* Hypersensitivity to latex.
* Acute disease at the time of enrolment.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests.
* Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period (up to Month 24).

Primary outcomes:
measure: Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies
timeFrame: One month after vaccination with the last dose of the Cervarix vaccine (Cervarix 1/Placebo Group: Month 3; Other groups: Month 7).
measure: Number of Subjects With Report of Any, and Grade 3 Solicited Local Symptoms
timeFrame: Within 7 days (Day 0-6) after vaccination.
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: Within 7 days (Day 0-6) after vaccination.
Secondary outcomes:
measure: Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies .
timeFrame: At Month 3, 1 month after the second dose of vaccine or placebo
measure: Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies
timeFrame: At Month 7, 1 month after the last dose of vaccine or placebo.
measure: Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies
timeFrame: At Month 12, at Month 18, at Month 24, at Month 36, and at Month 48 during the safety follow-up phase.
measure: Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies
timeFrame: At Month 7, 1 month after the last dose of vaccine or placebo.
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.
timeFrame: At Month 7 (M7)
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.
timeFrame: At Month 7 (M7)
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.
timeFrame: At Month 7 (M7)
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.
timeFrame: At Month 7 (M7)
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.
timeFrame: At Month 7 (M7)
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.
timeFrame: At Month 7 (M7)
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.
timeFrame: At Month 7 (M7)
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.
timeFrame: At Month 7 (M7)
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.
timeFrame: At Month 7 (M7)
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.
timeFrame: At Month 7 (M7)
measure: Number of Subjects Reporting Clinically Relevant Abnormalities in Biochemical and Haematological Laboratory Parameters Assessed.
timeFrame: At Month 7 (M7)
measure: Number of Seroconverted Subjects Against Human Papillomavirus 16 (HPV-16) and Human Papillomavirus 18 (HPV-18)
timeFrame: At Month 12, at Month 18, at Month 24, at Month 36, and at Month 48 during the safety follow-up phase.
measure: Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies
timeFrame: At Month 60 of the safety follow-up phase
measure: Number of Seroconverted Subjects Against Human Papillomavirus 16 (HPV-16) and Human Papillomavirus 18 (HPV-18)
timeFrame: At Month 60 of the safety follow-up phase
measure: Number of Subjects With Pregnancy Outcomes.
timeFrame: From Month 0 to Month 48.
measure: Number of Subjects With Pregnancy Outcomes.
timeFrame: Throughout the study period, from Month 0 to Month 60.
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs).
timeFrame: Within 30 days (Day 0-29) after vaccination.
measure: Number of Subjects With Medically Significant Conditions (MSCs).
timeFrame: From Month 0 to Month 7.
measure: Number of Subjects With Medically Significant Conditions (MSCs).
timeFrame: From Month 0 to Month 48.
measure: Number of Subjects With Medically Significant Conditions (MSCs).
timeFrame: Throughout the study period, from Month 0 to Month 60.
measure: Number of Subjects With New Onset of Autoimmune Diseases (NOADs)
timeFrame: From Month 0 to Month 7.
measure: Number of Subjects With New Onset of Autoimune Diseases (NOADs)
timeFrame: From Month 0 to Month 48.
measure: Number of Subjects With New Onset of Autoimmune Diseases (NOADs)
timeFrame: Throughout the study period, from Month 0 to Month 60.
measure: Number of Subjects With New Onset of Chronic Diseases (NOCDs)
timeFrame: From Month 0 to Month 7.
measure: Number of Subjects With New Onset of Chronic Diseases (NOCDs)
timeFrame: From Month 0 to Month 48.
measure: Number of Subjects With New Onset of Chronic Diseases (NOCDs)
timeFrame: Throughout the study period, from Month 0 to Month 60.
measure: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: From Month 0 to Month 7.
measure: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: From Month 0 to Month 48.
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: Throughout the study period, from Month 0 to Month 60.
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Langley
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: St. John's
country: Canada
facility: GSK Investigational Site
state: Newfoundland and Labrador
city: Truro
country: Canada
facility: GSK Investigational Site
state: Nova Scotia
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Karlsruhe
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Kehl
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Rheinstetten
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Tauberbischofsheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Weilheim
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Wuerzburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Wolfenbuettel
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Trier
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Flensburg
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Nordhausen
country: Germany
facility: GSK Investigational Site
state: Thueringen
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Romanowski B, Schwarz TF, Ferguson LM, Peters K, Dionne M, Schulze K, Ramjattan B, Hillemanns P, Catteau G, Dobbelaere K, Schuind A, Descamps D. Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose schedule compared with the licensed 3-dose schedule: results from a randomized study. Hum Vaccin. 2011 Dec;7(12):1374-86. doi: 10.4161/hv.7.12.18322. Epub 2011 Dec 1.
citation: Folschweiller N, Behre U, Dionne M, Durando P, Esposito S, Ferguson L, Ferguson M, Hillemanns P, McNeil SA, Peters K, Ramjattan B, Schwarz TF, Supparatpinyo K, Suryakirian PV, Janssens M, Moris P, Decreux A, Poncelet S, Struyf F. Long-term Cross-reactivity Against Nonvaccine Human Papillomavirus Types 31 and 45 After 2- or 3-Dose Schedules of the AS04-Adjuvanted Human HPV-16/18 Vaccine. J Infect Dis. 2019 May 5;219(11):1799-1803. doi: 10.1093/infdis/jiy743.
citation: Romanowski B, Schwarz TF, Ferguson L, Peters K, Dionne M, Behre U, Schulze K, Hillemanns P, Suryakiran P, Thomas F, Struyf F. Sustained immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine administered as a two-dose schedule in adolescent girls: Five-year clinical data and modeling predictions from a randomized study. Hum Vaccin Immunother. 2016;12(1):20-9. doi: 10.1080/21645515.2015.1065363. Epub 2015 Jul 15.
citation: Boxus M, Lockman L, Fochesato M, Lorin C, Thomas F, Giannini SL. Antibody avidity measurements in recipients of Cervarix vaccine following a two-dose schedule or a three-dose schedule. Vaccine. 2014 May 30;32(26):3232-6. doi: 10.1016/j.vaccine.2014.04.005. Epub 2014 Apr 13.
citation: Romanowski B, Schwarz TF, Ferguson LM, Ferguson M, Peters K, Dionne M, Schulze K, Ramjattan B, Hillemanns P, Behre U, Suryakiran P, Thomas F, Struyf F. Immune response to the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose or 3-dose schedule up to 4 years after vaccination: results from a randomized study. Hum Vaccin Immunother. 2014;10(5):1155-65. doi: 10.4161/hv.28022. Epub 2014 Feb 27.