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

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)

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.

Study Overview

• Status: Completed
• Conditions: Infections, Papillomavirus
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 383
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • GSK Investigational Site
  • Gent, Belgium, 9000
    • GSK Investigational Site
  • Leuven, Belgium, 3000
    • GSK Investigational Site
  • Liège, Belgium, 4000
    • GSK Investigational Site
  • Roeselare, Belgium, 8800
    • GSK Investigational Site
  • Wilrijk, Belgium, 2610
    • GSK Investigational Site
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • GSK Investigational Site
    • Golden, Colorado, United States, 80401
      • GSK Investigational Site
  • Rhode Island
    • Kingston, Rhode Island, United States, 02881
      • GSK Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • GSK Investigational Site
    • Salt Lake City, Utah, United States, 84121
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 25 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: HPV-16/18 Group; 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; 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.
Experimental: HPV-TETRA A Group; 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; 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.
Experimental: HPV-TETRA B Group; 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; 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.
Experimental: HPV-TETRA C Group; 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; 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.
Experimental: HPV-TETRA D Group; 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; 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.
Experimental: HPV-TETRA E Group; 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; 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.
Experimental: HPV-TETRA F Group; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Van Damme P, Leroux-Roels G, Simon P, Foidart JM, Donders G, Hoppenbrouwers K, Levin M, Tibaldi F, Poncelet S, Moris P, Dessy F, Giannini SL, Descamps D, Dubin G. Effects of varying antigens and adjuvant systems on the immunogenicity and safety of investigational tetravalent human oncogenic papillomavirus vaccines: results from two randomized trials. Vaccine. 2014 Jun 17;32(29):3694-705. doi: 10.1016/j.vaccine.2014.03.040. Epub 2014 Mar 25.

Helpful Links

• 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 record dates

Study Major Dates

• Study Start (Actual): March 4, 2005
• Primary Completion (Actual): March 27, 2006
• Study Completion (Actual): March 27, 2006

Study Registration Dates

• First Submitted: October 3, 2005
• First Submitted That Met QC Criteria: October 3, 2005
• First Posted (Estimate): October 4, 2005

Study Record Updates

• Last Update Posted (Actual): December 12, 2019
• Last Update Submitted That Met QC Criteria: November 25, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 102115; 2004-003766-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD is available via the Clinical Study Data Request site (click on the link provided below).
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below).
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Dataset Specification
   Information identifier: 102115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 102115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 102115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 102115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register. The results of this study 102115 are summarised with studies 107919 and 108052 on the GSK Clinical Study Register.
5. Informed Consent Form
   Information identifier: 102115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 102115
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register