Human Papilloma Virus Vaccine Immunogenicity and Safety Trial in Young Adult Women With GSK Bio's Novel HPV Vaccine.

Study Overview
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Brief Summary
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Human Papilloma viruses (HPV) are viruses that cause infections of the skin and genitals in men and women. Several types of HPV infection are transmitted by sexual activity and, in women, can infect the cervix (part of the uterus or womb). This infection, if it persists, can lead over a long period of time to cancer of the cervix in women. In collaboration with MedImmune Inc., GlaxoSmithKline Biologicals has developed a HPV vaccine against the oncogenic types HPV-16 and HPV-18 formulated with the adjuvant AS04. GSK Biologicals is also evaluating novel HPV vaccine formulations.This study will evaluate the immunogenicity and safety of a novel GSK Biologicals HPV vaccine in women 18-25 years of age at study start. Approximately 376 study subjects will receive the novel HPV vaccine or the control vaccine administered intramuscularly according to a 0-1-6 month schedule.

Official Title
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A Dose-range Study to Assess the Safety and Immunogenicity of a Novel HPV Vaccine When Administered Intramuscularly According to a 3-dose Schedule (0,1,6-month) in Healthy Adult Females (18-25 Years of Age)

Conditions
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Infections, Papillomavirus

Intervention / Treatment
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* Biological: HPV 16/18 L1 AS04
* Biological: HPV-16/18/31/45 L1 AS04 Formulation 1
* Biological: HPV-16/18/31/45 L1 AS04 Formulation 2
* Biological: HPV-16/18/31/45 L1 AS04 Formulation 3
* Biological: HPV-16/18/31/45 L1 AS04 Formulation 4
* Biological: HPV-16/18/31/45 L1 AS04 Formulation 5
* Biological: HPV-16/18/31/45 L1 AS04 Formulation 6


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A woman between, and including, 18 and 25 years of age at the time of the first vaccination Written informed consent from the subject prior to enrolment Subject must be free of obvious health problems Subject must be of non-childbearing potential and have had no more than 6 lifetime sexual partners Exclusion Criteria: Pregnant or breastfeeding A woman planning to become pregnant or planning to discontinue contraceptive precautions during approximately the first nine months of the study (Month 0-8) Known acute or chronic, clinically significant pulmonary, cardiovascular, neurologic, hepatic or renal functional abnormality History of chronic condition(s) requiring treatment such as cancer, chronic hepatitis or kidney disease(s), diabetes, or autoimmune disease Previous vaccination against human papillomavirus (HPV)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 25 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HPV-16/18 Group<br>Female subjects who received 3 doses of the HPV-16/18 L1 AS04 vaccine intramuscularly, into the deltoid of the non-dominant arm according to a 3-dose 0, 1, 6-month vaccination schedule. | Biological: HPV 16/18 L1 AS04<br>* 3 doses of 0.6 mL supplied as a liquid in individual pre-filled syringes administered intramuscularly in the deltoid muscle of the non-dominant arm, at Day 0, Month 1 and Month 6.<br>|
| Experimental: HPV-TETRA A Group<br>Female subjects who received 3 doses of the HPV-16/18/31/45 L1/AS04 vaccine, formulation 1 intramuscularly, into the deltoid of the non-dominant arm according to a 3-dose 0, 1, 6-month vaccination schedule. | Biological: HPV-16/18/31/45 L1 AS04 Formulation 1<br>* 3 doses of 0.6 mL supplied as a liquid in individual pre-filled syringes administered intramuscularly in the deltoid muscle of the non-dominant arm, at Day 0, Month 1 and Month 6.<br>|
| Experimental: HPV-TETRA B Group<br>Female subjects who received 3 doses of the HPV-16/18/31/45 L1/AS04 vaccine, formulation 2 intramuscularly, into the deltoid of the non-dominant arm according to a 3-dose 0, 1, 6-month vaccination schedule. | Biological: HPV-16/18/31/45 L1 AS04 Formulation 2<br>* 3 doses of 0.6 mL supplied as a liquid in individual pre-filled syringes administered intramuscularly in the deltoid muscle of the non-dominant arm, at Day 0, Month 1 and Month 6.<br>|
| Experimental: HPV-TETRA C Group<br>Female subjects who received 3 doses of the HPV-16/18/31/45 L1/AS04 vaccine, formulation 3 intramuscularly, into the deltoid of the non-dominant arm according to a 3-dose 0, 1, 6-month vaccination schedule. | Biological: HPV-16/18/31/45 L1 AS04 Formulation 3<br>* 3 doses of 0.6 mL supplied as a liquid in individual pre-filled syringes administered intramuscularly in the deltoid muscle of the non-dominant arm, at Day 0, Month 1 and Month 6.<br>|
| Experimental: HPV-TETRA D Group<br>Female subjects who received 3 doses of the HPV-16/18/31/45 L1/AS04 vaccine, formulation 4 intramuscularly, into the deltoid of the non-dominant arm according to a 3-dose 0, 1, 6-month vaccination schedule. | Biological: HPV-16/18/31/45 L1 AS04 Formulation 4<br>* 3 doses of 0.6 mL supplied as a liquid in individual pre-filled syringes administered intramuscularly in the deltoid muscle of the non-dominant arm, at Day 0, Month 1 and Month 6.<br>|
| Experimental: HPV-TETRA E Group<br>Female subjects who received 3 doses of the HPV-16/18/31/45 L1/AS04 vaccine, formulation 5 intramuscularly, into the deltoid of the non-dominant arm according to a 3-dose 0, 1, 6-month vaccination schedule. | Biological: HPV-16/18/31/45 L1 AS04 Formulation 5<br>* 3 doses of 0.6 mL supplied as a liquid in individual pre-filled syringes administered intramuscularly in the deltoid muscle of the non-dominant arm, at Day 0, Month 1 and Month 6.<br>|
| Experimental: HPV-TETRA F Group<br>Female subjects who received 3 doses of the HPV-16/18/31/45 L1/AS04 vaccine, formulation 6 intramuscularly, into the deltoid of the non-dominant arm according to a 3-dose 0, 1, 6-month vaccination schedule. | Biological: HPV-16/18/31/45 L1 AS04 Formulation 6<br>* 3 doses of 0.6 mL supplied as a liquid in individual pre-filled syringes administered intramuscularly in the deltoid muscle of the non-dominant arm, at Day 0, Month 1 and Month 6.<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 Papillomavirus (Anti-HPV)-16 at Month 7 | Seroconversion was defined as the appearance of anti-HPV-16 antibodies [i.e. antibody titer greater than or equal to (≥) the cut-off value] in the serum of subjects seronegative before vaccination. The cut-off value was 8 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). | At Month 7 | 
| Number of Seroconverted Subjects for Anti-HPV-18 at Month 7 | Seroconversion was defined as the appearance of anti-HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the serum of subjects seronegative before vaccination. The cut-off value was 7 EL.U/mL. | At Month 7 | 
| Anti-HPV-16 Antibody Titers Assessed by ELISA at Month 7 | Anti-HPV-16 antibody titers were presented as Geometric Mean Titers (GMT) and expressed in EL.U/mL. | At Month 7 | 
| Anti-HPV-18 Antibody Titers Assessed by ELISA at Month 7 | Anti-HPV-18 antibody titers were presented as Geometric Mean Titers and expressed in EL.U/mL. | At Month 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for Anti-HPV-16 at Month 2 | Seroconversion was defined as the appearance of anti-HPV-16 antibodies (i.e. antibody titer ≥ cut-off value) in the serum of subjects seronegative before vaccination. The cut-off value was 8 EL.U/mL. | At Month 2 | 
| Number of Seroconverted Subjects for Anti-HPV-18 at Month 2 | Seroconversion was defined as the appearance of anti-HPV-18 antibodies (i.e. antibody titer ≥ cut-off value) in the serum of subjects seronegative before vaccination. The cut-off value was 7 EL.U/mL. | At Month 2 | 
| Anti-HPV-16 Antibody Titers Assessed by ELISA at Month 2 | Anti-HPV-16 antibody titers were presented as Geometric Mean Titers and expressed in EL.U/mL. | At Month 2 | 
| Anti-HPV-18 Antibody Titers Assessed by ELISA at Month 2 | Anti-HPV-18 antibody titers were presented as Geometric Mean Titers and expressed in EL.U/mL. | At Month 2 | 
| Number of Seroconverted Subjects for Anti-HPV-31 at Months 2 and 7 | Seroconversion was defined as the appearance of anti-HPV-31 antibodies (i.e. antibody titer ≥ cut-off value) in the serum of subjects seronegative before vaccination. The cut-off value was 59 EL.U/mL. | At Month 2 and Month 7 | 
| Number of Seroconverted Subjects for Anti-HPV-45 at Months 2 and 7 | Seroconversion was defined as the appearance of anti-HPV-45 antibodies (i.e. antibody titer ≥ cut-off value) in the serum of subjects seronegative before vaccination. The cut-off value was 59 EL.U/mL. | At Month 2 and Month 7 | 
| Anti-HPV-31 Antibody Titers Assessed by ELISA at Months 2 and 7 | Anti-HPV-31 antibody titers were presented as Geometric Mean Titers and expressed in EL.U/mL. | At Month 2 and Month 7 | 
| Anti-HPV-45 Antibody Titers Assessed by ELISA at Months 2 and 7 | Anti-HPV-45 antibody titers were presented as Geometric Mean Titers and expressed in EL.U/mL. | At Month 2 and Month 7 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any solicited local symptom regardless of their intensity grade. Grade 3 pain = significant pain at rest, that prevented normal every day activity. Grade 3 redness/swelling = redness/swelling above 50 millimeters (mm). All the reported local symptoms are considered related to the vaccination in the study. | During the 7 day post-vaccination period following each dose and across doses | 
| 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 any solicited general symptom regardless of intensity grade or relationship to vaccination. Any Fever = axillary temperature greater than or equal to (≥) 37.5 degrees Celsius (°C). Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever greater than (>) 39.0°C. Related = general symptom assessed by the investigator as causally related to the vaccination. | During the 7 day post-vaccination period following each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | An unsolicited adverse event (AE) was defined as any AE reported in addition to those solicited during the clinical study. Also, any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event. Any is defined as the occurrence of any unsolicited AE irrespective of its intensity grade and relationship to vaccination. Grade 3 unsolicited AE = an AE that prevented normal, everyday activities. Related AE = an AE assessed by the investigator as causally related to the study vaccination. | During the 30-day post-vaccination period | 
| Number of Subjects With Any Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination. | From Day 0 to Month 7 | 
| Number of Subjects With Any SAEs During the Extended Safety Follow-up | SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination. | From Day 0 to Month 12 | 
| Number of Subjects Reporting Pregnancies and Outcomes of Reported Pregnancies | Outcomes of reported pregnancies were: Healthy baby, Spontaneous abortion, Elective abortion. | From Day 0 to Month 12 | 
| 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. | From Day 0 up to Month 12 | 
| 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. | From Day 0 up to Month 12 | 
| Number of Subjects With Clinically Relevant Abnormalities in Biochemical and Haematological Parameters | The parameters assessed were both biochemical (alanine aminotransferase = ALAT, creatinine = CREA, blood urea nitrogen = BUN) and haematological [basophils = BAS, eosinophils = EOS, red blood cells = RBC, hematocrit = HCT, hemoglobin = HGB, leukocytes (white blood cells) = WBC, lymphocytes = LYM, monocytes = MONO, neutrophils = NEU and platelets = PLA]. Abnormal values of a parameter at Months 2 and 7 are defined as below and above the normal ranges, as compared to the baseline status of the same parameter. | At Month 2 and Month 7 |