Immunogenicity and Safety of GlaxoSmithKline Biologicals' Huma Papillomavirus (HPV) Vaccine 580299 in Healthy Females 15 - 25 Years of Age

• ClinicalTrials.gov Identifier: NCT00552279
• Recruitment Status: Completed
• First Posted: November 1, 2007
• Results First Posted: March 5, 2010
• Last Update Posted: June 25, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. The current phase 3b study is designed to assess the immunogenicity and safety of GlaxoSmithKline Biologicals' HPV vaccine GSK580299 administered according to an alternative dosing schedule as compared to the standard dosing schedule in young female subjects aged 15 - 25 years. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Condition or disease	Intervention/treatment	Phase
Infections, Papillomavirus	Biological: Cervarix TM	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 805 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety Study of GlaxoSmithKline Biologicals' HPV Vaccine GSK580299 Administered According to an Alternative Dosing Schedule as Compared to the Standard Dosing Schedule in Young Female Subjects Aged 15-25 Years
• Study Start Date: November 12, 2007
• Actual Primary Completion Date: February 26, 2009
• Actual Study Completion Date: July 20, 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cervarix-12 Group; Women received 3 doses of Cervarix TM (human papillomavirus (HPV) vaccine) administered according to a 0, 1, 12-month schedule	Biological: Cervarix TM; Intramuscular administration into the deltoid region of the non-dominant arm according to a 0, 1, 12-month schedule.; Other Name: HPV vaccine (GSK580299)
Active Comparator: Cervarix-6 Group; Women received 3 doses of Cervarix TM (HPV vaccine) administered according to a 0, 1, 6-month schedule.	Biological: Cervarix TM; Intramuscular administration into the deltoid region of the non-dominant arm according to a 0, 1, 6-month schedule.

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies [ Time Frame: One month after the third vaccine dose ]

   Seroconversion is defined as the appearance of anti-HPV-16 and/or anti- HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination.

   Cut-off values were 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.

2. Titer of Anti-HPV-16 and Anti-HPV-18 Antibodies [ Time Frame: One month after the third vaccine dose ]
   Titer given as geometric mean titer (GMT).

Secondary Outcome Measures :

1. Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies [ Time Frame: One month after the second vaccine dose ]

   Seroconversion is defined as the appearance of anti-HPV-16 and/or anti- HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the sera of subjects seronegative before vaccination.

   Cut-off values were 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.

2. Titer of Anti-HPV-16 and Anti-HPV-18 Antibodies [ Time Frame: One month after the second vaccine dose ]
   Titer given as GMT.
3. Number of Subjects Reporting Solicited Local Symptoms [ Time Frame: During the 7-day (Days 0-6) period following each vaccination ]
   Solicited local symptoms assessed include pain, redness and swelling at the injection site.
4. Number of Subjects Reporting Solicited General Symptoms [ Time Frame: During the 7-day (Days 0-6) period following each vaccination ]
   Solicited general symptoms assessed include arthralgia, fatigue, fever, gastrointestinal symptoms, headache, myalgia, rash, and urticaria.
5. Number of Subjects Reporting Unsolicited Adverse Events (AE) [ Time Frame: During the 30-day (Days 0-29) period following each vaccination ]
   An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
6. Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs), New Onset Autoimmune Diseases (NOADs), Serious Adverse Events (SAEs), and Medically Significant Conditions (MSCs) [ Time Frame: During the entire study period (up to Month 18 or up to Month 12) ]

   Entire study period = up to Month 18 Cervarix-12 & Month 12 Cervarix-6.

   NOCDs assessed include eg. autoimmune disorders (NOADs), asthma, type I diabetes. MSCs assessed include AEs prompting emergency room visits and physician office visits not related to common illnesses.

   An SAE is any untoward medical occurrence that: results in death, is lifethreatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.

7. Number of Subjects With Pregnancies and Their Outcomes [ Time Frame: During the entire study period (up to Month 18 or Month 12) ]

   Entire study period = up to Month 18 Cervarix-12 & Month 12 Cervarix-6

   Number of pregnancies and pregnancy outcomes.

8. Number of Subjects Completing the 3-dose Vaccination Schedule [ Time Frame: After the third vaccine dose ]

Eligibility Criteria

• Ages Eligible for Study: 15 Years to 25 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Subjects who the investigator believes that they and/or their parent(s)/Legally acceptable representative(s) (LAR) can and will comply with the requirements of the protocol
• A female between and including 15 and 25 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject prior to enrolment. For subjects below the legal age of consent, written informed consent must be obtained from the subject's parents/legally acceptable representative (LAR), and written informed assent must be obtained from the subject.
• Healthy subjects as established by medical history and/or clinical examination before entering into the study.
• Subject must be of non-childbearing potential, or if she is of child bearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative urine pregnancy test and continue such precautions for 2 months after completion of the vaccination series.
• Subject who had no more than 6 lifetime sexual partners prior to enrolment.

Exclusion Criteria:

• Use of any investigational or non-registered product (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.
• 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. 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 patient is outside of specified window.
• 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).
• Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period.
• previous administration of components of the investigational vaccine
• Cancer or autoimmune disease under treatment.
• 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.
• Hypersensitivity to latex
• Acute disease at the time of enrolment.
• Administration of immunoglobulins and/or any blood products within the three months preceding blood sampling.
• Pregnant or breastfeeding female.
• Female planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the study period starting at visit one and up to two months after the last vaccine dose.
• Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal function abnormality as determined by physical examination or lab tests.

Contacts and Locations

Locations

Italy

GSK Investigational Site

Brescia, Lombardia, Italy, 25123

GSK Investigational Site

Lodi, Lombardia, Italy, 26900

GSK Investigational Site

Milano, Lombardia, Italy, 20122

GSK Investigational Site

Cagliari, Sardegna, Italy, 09127

GSK Investigational Site

Sassari, Sardegna, Italy, 07100

GSK Investigational Site

Palermo, Sicilia, Italy, 90127

GSK Investigational Site

Ragusa, Sicilia, Italy, 97100

Romania

GSK Investigational Site

Bucharest, Romania, 010507

GSK Investigational Site

Bucharest, Romania, 077190

GSK Investigational Site

Bucharest, Romania, 22102

GSK Investigational Site

Cluj-Napoca, Romania, 400217

GSK Investigational Site

Sibiu, Romania, 550245

GSK Investigational Site

Sibiu, Romania

Slovakia

GSK Investigational Site

Dolny Kubin, Slovakia, 026 01

GSK Investigational Site

Nova Dubnica, Slovakia, 018 51

GSK Investigational Site

Trencin, Slovakia, 911 01

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. 

Study Data/Documents: Individual Participant Data Set 

Identifier: 109179
For additional information about this study please refer to the GSK Clinical Study Register

Informed Consent Form 

Identifier: 109179
For additional information about this study please refer to the GSK Clinical Study Register

Study Protocol 

Identifier: 109179
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: 109179
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: 109179
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: 109179
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 109179
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Esposito S, Birlutiu V, Jarcuska P, Perino A, Man SC, Vladareanu R, Meric D, Dobbelaere K, Thomas F, Descamps D. Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted vaccine administered according to an alternative dosing schedule compared with the standard dosing schedule in healthy women aged 15 to 25 years: results from a randomized study. Pediatr Infect Dis J. 2011 Mar;30(3):e49-55. doi: 10.1097/INF.0b013e318206c26e.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00552279
• Other Study ID Numbers: 109179
• First Posted: November 1, 2007
• Results First Posted: March 5, 2010
• Last Update Posted: June 25, 2018
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.

Keywords provided by GlaxoSmithKline:

HPV; cervical cancer; papillomavirus; Human papillomavirus (HPV) vaccine

Additional relevant MeSH terms:

Vaccines; Immunologic Factors; Physiological Effects of Drugs