Evaluation of the Immune Responses of GSK Biologicals' HPV Vaccine Following Manufacturing Process Adaptation.

Assess Lot-to-lot Consistency of GSK Biologicals' HPV-16/18 L1/AS04 Vaccine Following Manufacturing Adjustments Administered Intramuscularly According to a 0,1,6-mth Schedule in Healthy Female Subjects (18-25 y)

Human papillomavirus infection has clearly been recognized as the cause of cervical cancer. Indeed, the infection of the cervix by certain oncogenic types of HPV, if not cleared , can lead over time to cervical cancer in women . This study will compare the immune response induced by different lots of the HPV-16/18 L1/AS04 vaccine, following adjustments to the manufacturing process.

Study Overview

• Status: Completed
• Conditions: Infections, Papillomavirus; Papillomavirus Vaccines
• Intervention / Treatment: Biological: Cervarix™

• Study Type: Interventional
• Enrollment (Actual): 798
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark, DK-2650
    • GSK Investigational Site
• Lithuania
  • Kaunas, Lithuania, LT-50009
    • GSK Investigational Site
  • Klaipeda, Lithuania, LT-93200
    • GSK Investigational Site
  • Vilnius, Lithuania, LT-07156
    • GSK Investigational Site
  • Vilnius, Lithuania, LT-10207
    • GSK Investigational Site
• Poland
  • Krakow, Poland, 31-501
    • GSK Investigational Site
  • Poznan, Poland, 60-533
    • GSK Investigational Site
  • Warszawa, Poland, 01-211
    • 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 female subject between, and including, 18 and 25 years of age at the time of the first vaccination.
• Written informed consent obtained from the subject prior to enrolment.
• Subject must have a negative urine pregnancy test.
• Healthy subject before entering the study entry as established by medical history and physical examination.
• Subject must be of non-childbearing potential.

Exclusion Criteria:

• pregnant or breastfeeding subject.
• previous vaccination against human papillomavirus (HPV).
• Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality.
• History of chronic condition(s) requiring treatment such as cancer, chronic hepatic or kidney disease(s), diabetes or autoimmune disease.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cervarix Lot1 Group; Subjects aged between and including 18-25 years, who received one dose of Cervarix™ vaccine Lot 1 manufactured at 600L scale according to a 0, 1, 6- month schedule and were followed up for 7 months after the first dose. Additionally, a telephone contact was foreseen at Month 12. The vaccine was administrated by intramuscular (IM) injection into the deltoid region of the non-dominant arm.	Biological: Cervarix™; GSK Biologicals' vaccine against human papillomaviruses 16 and 18.
Experimental: Cervarix Lot2 Group; Subjects aged between and including 18-25 years, who received one dose of Cervarix™ vaccine Lot 2 manufactured at 600L scale according to a 0, 1, 6- month schedule and were followed up for 7 months after the first dose. Additionally, a telephone contact was foreseen at Month 12. The vaccine was administrated by intramuscular (IM) injection into the deltoid region of the non-dominant arm.	Biological: Cervarix™; GSK Biologicals' vaccine against human papillomaviruses 16 and 18.
Experimental: Cervarix Lot3 Group; Subjects aged between and including 18-25 years, who received one dose of Cervarix™ vaccine Lot 3 manufactured at 600L scale according to a 0, 1, 6- month schedule and were followed up for 7 months after the first dose. Additionally, a telephone contact was foreseen at Month 12. The vaccine was administrated by intramuscular (IM) injection into the deltoid region of the non-dominant arm.	Biological: Cervarix™; GSK Biologicals' vaccine against human papillomaviruses 16 and 18.
Experimental: Cervarix Low Group; Subjects aged between and including 18-25 years, who received one dose of Cervarix™ vaccine manufactured lower scale-80L according to a 0, 1, 6- month schedule and were followed up for 7 months after the first dose. Additionally, a telephone contact was foreseen at Month 12. The vaccine was administrated by intramuscular (IM) injection into the deltoid region of the non-dominant arm.	Biological: Cervarix™; GSK Biologicals' vaccine against human papillomaviruses 16 and 18.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Seroconverted (SCR) Subjects for Anti-Human Papillomavirus Type 16 (Anti-HPV-16) and Anti-Human Papillomavirus Type 18 (Anti-HPV-18)	Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (anti-HPV-16 concentrations ≥8 Enzyme-Linked Immunosorbent Assay [ELISA] units per milliliter [EL.U/mL] and anti-HPV-18 concentrations ≥7 EL.U/mL) in the serum of subjects seronegative before vaccination.	At Month 7
Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18	Seropositivity defined subjects with anti-HPV-16 antibody concentration ≥ 8 EL.U/mL and/or anti-HPV-18 antibody concentration ≥ 7 EL.U/mL.	At Month 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	From Month 0 to Month 12
Number of SCR Subjects for Anti-HPV-16 and Anti-HPV-18	Seroconversion was defined as the appearance of anti-HPV-16 and/or anti-HPV-18 antibodies (anti-HPV-16 concentrations ≥8 ELISA units per milliliter [EL.U/mL] and anti-HPV-18 concentrations ≥7 EL.U/mL) in the serum of subjects seronegative before vaccination.	At Month 2
Number of Seropositive Subjects for Anti-HPV-16 and Anti-HPV-18	Seropositivity defined subjects with anti-HPV-16 antibody concentration ≥ 8 EL.U/mL and/or anti-HPV-18 antibody concentration ≥ 7 EL.U/mL .	At Month 2
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 millimeters (mm) diameter of injection site.	During the 7-days (Day 0-6) post-vaccination
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], gastro-intestinal, 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 > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. Arthralgia (joint pain) = pain occurring in joints that were distal from the injection site. This outcome presents solicited general symptoms post dose 1 of vaccination.	During the 7-days (Day 0-6) post-vaccination
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], gastro-intestinal, 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 > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. Arthralgia (joint pain) = pain occurring in joints that were distal from the injection site. This outcome presents solicited general symptoms post dose 2 of vaccination.	During the 7-days (Day 0-6) post-vaccination
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], gastro-intestinal, 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 > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. Arthralgia (joint pain) = pain occurring in joints that were distal from the injection site. This outcome presents solicited general symptoms post dose 3 of vaccination.	During the 7-days (Day 0-6) post-vaccination
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	Assessed solicited general symptoms were arthralgia, fatigue, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)], gastro-intestinal, 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 > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. Arthralgia (joint pain) = pain occurring in joints that were distal from the injection site. This outcome presents results across vaccination doses for solicited general symptoms.	During the 7-days (Day 0-6) post-vaccination
Number of Subjects With New Onset Chronic Diseases (NOCDs)	NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.	From Month 0 to Month 7
Number of Subjects With Medically Significant Adverse Events (MSAEs)	MSAEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.	From Month 0 to Month 7
Number of Subjects With (NOCDs)	NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.	From Month 0 to Month 12
Number of Subjects With MSAEs	MSAEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.	From Month 0 to Month 12
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.	Within 30 days (Day 0-29) post vaccination
Number of Subjects With Serious Adverse Events (SAEs)	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	From Month 0 to Month 7

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Descamps D, Hardt K, Spiessens B, Izurieta P, Verstraeten T, Breuer T, Dubin G. Safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine for cervical cancer prevention: a pooled analysis of 11 clinical trials. Hum Vaccin. 2009 May;5(5):332-40. doi: 10.4161/hv.5.5.7211. Epub 2009 May 20.

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): October 28, 2005
• Primary Completion (Actual): March 1, 2007
• Study Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: November 7, 2005
• First Submitted That Met QC Criteria: November 7, 2005
• First Posted (Estimate): November 8, 2005

Study Record Updates

• Last Update Posted (Actual): January 2, 2020
• Last Update Submitted That Met QC Criteria: December 27, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Other Study ID Numbers: 104772; 2005-001667-58 (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. Clinical Study Report
   Information identifier: 104772
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 104772
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 104772
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 104772
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 104772
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 104772
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: 104772
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register