Human Papilloma Virus (HPV) Vaccine Immunogenicity and Safety Trial in Young and Adult Women With GSK Biologicals' HPV-16/18

Study Overview
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Brief Summary
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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 immunogenicity and safety of GSK Biologicals HPV-16/18 vaccine over 12 months, in women up to 55 years of age at study start. Approximately 660 study subjects will receive the HPV vaccine administered intramuscularly according to a 0-1-6 month schedule. The study will be extended to assess long-term safety and immunogenicity of the HPV-16/18 vaccine.

Official Title
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Phase 3, Open, Age-stratified Study to Assess Immunogenicity and Safety of GSK Biologicals' HPV-16/18 Vaccine Administered Intramuscularly According to 3-dose Schedule (0,1,6 Months) in Healthy Female Subjects Aged 15 - 55 Years and Long Term Follow-up

Conditions
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Infections, Papillomavirus

Intervention / Treatment
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* Biological: Cervarix


Participation Criteria
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Eligibility Criteria
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Inclusion criteria for primary study: A woman who the investigator believes that she and/or her parents/legally acceptable representative can and will comply with the requirements of the protocol. A woman between, and including, 15 and 55 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 a parent or legally acceptable representative and, in addition, the subject should sign and personally date a written informed assent). Free of obvious health problems. Subject must have a negative urine pregnancy test. Subject must be of non-childbearing potential or, if of childbearing potential, she must be abstinent or must be using adequate contraceptive precautions for 30 days prior to vaccination and must agree to continue such precautions for two months after completion of the vaccination series. Subjects who reach menarche during the study and therefore become of childbearing potential must agree to follow the same precautions Inclusion criteria for extension studies A female who enrolled in the primary study and received three doses of vaccine. 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 a parent or legally acceptable representative and, in addition, the subject must sign and personally date a written informed assent). Exclusion criteria for primary study: Pregnant or breastfeeding. A woman planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the study period, up to two months after the last vaccine dose. 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 (up to Month 12). Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose, or planned administration during the study period. Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after the first dose of study 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. Previous administration of components of the investigational vaccine Previous vaccination against HPV. Any medically diagnosed or suspected immunodeficient condition based on medical history and physical examination. History of allergic disease, suspected allergy or reactions likely to be exacerbated by any component of the study vaccine. Hypersensitivity to latex. Known acute or chronic, clinically significant neurologic, 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 3 months preceding the first dose of study vaccine or planned administration during the study period. Enrolment will be deferred until the subject is outside of specified window. Acute disease at the time of enrolment. Exclusion criteria for extension studies Use of any investigational or non-registered product (drug or vaccine) or planned use during the study period. 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). Chronic administration of immunosuppressants or other immune-modifying drugs occurring less than 3 months prior to blood sampling. Administration of immunoglobulins and/or any blood products within the three months preceding blood sampling.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cervarix (15-25 Years) Group<br>Women aged 15 to 25 years received 3 doses of Cervarix vaccine administered according to a 0, 1, 6-month schedule. | Biological: Cervarix<br>* Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.<br>|
| Experimental: Cervarix (26-45 Years) Group<br>Women aged 26 to 45 years received 3 doses of Cervarix vaccine administered according to a 0, 1, 6-month schedule. | Biological: Cervarix<br>* Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.<br>|
| Experimental: Cervarix (46-55 Years) Group<br>Women aged 46 to 55 years received 3 doses of Cervarix vaccine administered according to a 0, 1, 6-month schedule. | Biological: Cervarix<br>* Three doses of vaccine administered intramuscularly according to a 0, 1, 6-month schedule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for Anti-human Papilloma Virus 16 (Anti-HPV-16) and Anti-human Papilloma Virus 18 (Anti-HPV-18) Antibodies, in Women 15 to 25 Years of Age and Women 26 to 45 Years of Age | Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies [i.e. antibody titer greater than or equal to (≥) the cut-off value] in the sera of subjects seronegative before vaccination. Cut-off values were 8 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies. Data for the Cervarix (46-55 Years) Group are presented in the Secondary Outcomes as per Protocol. | At Month 7 | 
| Anti-HPV-16/18 Antibody Titers Assessed by ELISA Based on the ATP Cohort for Immunogenicity at Months 18, 24, 36 and 48 | Anti-HPV 16/18 antibody titers were detected in sera samples and presented as Geometric Mean Titers (GMT), expressed in EL.U/mL. Data for pre-vaccination, Month 2, Month 7 and Month 12 are presented in the Secondary Outcomes as per Protocol. | At Months 18, 24, 36 and 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies, in Women 46 - 55 Years of Age | Seroconversion was 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 EL.U/mL for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies. Seroconversion results at Month 7 for the Cervarix (15-25 Years) Group and for the Cervarix (26-45 Years) Group are presented in the Primary Outcome Measure 1. | At Month 7 | 
| Anti-HPV-16/18 Antibody Titers Assessed by ELISA Based on the ATP Cohort for Immunogenicity at Pre-vaccination (PRE) and Months 2, 7 and 12 | Anti-HPV 16/18 antibody titers were detected in sera samples and presented as GMT, expressed in EL.U/mL. Data for Months 18, 24, 36 and 48 are presented in the Primary Outcome Measure 2 as per Protocol. | At PRE and Months 2, 7 and 12 | 
| Number of Subjects Seroconverted for Anti-HPV-16 and Anti-HPV-18 Antibodies at Month 2 and Month 12 | Seroconversion was 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 EL.U/mL for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies. Seroconversion results at Month 7 are presented in the Primary Outcome Measure 1 for Cervarix (15-25 Years) Group and Cervarix (26-45 Years) Group and in the Secondary Outcome Measure 3 for the Cervarix (46-55 Years) Group. | At Month 2 and Month 12 | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were arthralgia, fatigue, fever, gastrointestinal symptoms, headache, myalgia, rash and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever above (>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimetres (mm) of injection site. | During the 7-day period (from the day of vaccination up to 6 subsequent days) following vaccination after each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | An unsolicited AE covers 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 and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination. | During the 30-day (from the day of vaccination up to 29 subsequent days) post-vaccination period | 
| Number of Subjects Reporting Serious Adverse Events (SAE) | An SAE is any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study subject, or may have evolved into one of the outcomes listed above. | During the entire study period (from Day 0 up to Month 48) | 
| Number of Subjects Reporting New Onset of Chronic Diseases (NOCDs) | NOCDs assessed include chronic diseases such as autoimmune disorders, diabetes, allergies also asthma and pathognomic signs/symptoms of these diseases. | During the entire study period (from Day 0 up to Month 48) | 
| Number of Subjects Reporting Medically Significant Conditions | Medically significant conditions are AEs prompting emergency room or physician visits that were not related to common diseases or routine visits for physical examination or vaccination, or SAEs that were not related to common diseases. | During the entire study period (from Day 0 up to Month 48) | 
| Anti-HPV-16/18 Antibody Titers Assessed by ELISA in a Subset of Subjects in Cervical Secretions (CVS) Samples | Anti-HPV 16/18 antibody titers were detected in CVS samples and presented as GMTs, expressed in EL.U/mL based on ELISA. | At Months 18 and 24 | 
| Number of Subjects Seropositive for Total Immunoglobulin-G (IgG) in Blood (Serum) and in Cervical Samples (Secretion) in a Subset of Subjects | Seropositivity was defined as total IgG ≥ 0 microgram per milliliter (µg/mL) and was detected in sera and in CVS samples by ELISA. | At Months 18 and 24 | 
| Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies | Outcomes of pregnancies were: Abnormal infant / Congenital anomaly, Elective termination, Missed abortion, Normal infant, Premature birth, Spontaneous abortion / Miscarriage and Outcome unknown. | During the entire study period (from Day 0 up to Month 48) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV Vaccine Safety