A Follow-up Extension Study to Evaluate the Persistence of Immune Response to GSK Biologicals' HPV Vaccine in Healthy Chinese Female Subjects Who Received Three Doses of the Vaccine in the HPV-058 Study

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03355820
• Collaborator: (none)
• Enrollment: 228
• Location: 1
• Arm: 1
• Actual Duration (Months): 4
• Patients Per Site Per Month: 57.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the persistence of immune response in subjects who received the HPV-16/18 vaccine, seven to eight years after the last dose of primary vaccination in the HPV-058 study. No new subjects will be enrolled in this extension study.

Condition or Disease	Intervention/Treatment	Phase
Cervical Intraepithelial Neoplasia	Procedure: Blood sampling for antibody determination	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 228 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Persistence of Immune Response to GSK Biologicals' HPV Vaccine in Healthy Chinese Female Subjects From the HPV-058 Study
• Actual Study Start Date: Feb 28, 2018
• Actual Primary Completion Date: Jun 29, 2018
• Actual Study Completion Date: Jun 29, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HPV Group Healthy Chinese female subjects, including and above 17 years of age at the time of enrollment, who received all three doses of the Cervarix vaccine in the HPV-058 (NCT00996125) primary study.	Procedure: Blood sampling for antibody determination; In order to assess the persistence of immune responses seven to eight years after the last vaccine dose against HPV-16/18, a blood sample (~5 mL) will be taken from all the subjects, at Day 1.

Outcome Measures

Primary Outcome Measures

1. Number of Seropositive Subjects for Anti-HPV-16 Antibodies at Day 1 in HPV-093 (NCT03355820) Study [At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study)]

   A seropositive subject is defined as a subject whose antibody concentration is equal to or above the cut-off value of 19 Enzyme Linked Immunosorbent Assay units per milliliter (EL.U/mL).

2. Number of Seropositive Subjects for Anti-HPV-18 Antibodies at Day 1 in HPV-093 (NCT03355820) Study [At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study)]

   A seropositive subject is defined as a subject whose antibody concentration is equal to or above the cut-off value of 18 EL.U/mL.

3. Anti-HPV-16 Antibody Concentrations at Day 1 in HPV-093 (NCT03355820) Study [At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study)]

   Anti-HPV-16 antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in EL.U/mL.

4. Anti-HPV-18 Antibody Concentrations at Day 1 in HPV-093 (NCT03355820) Study [At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study)]

   Anti-HPV-18 antibody concentrations are presented as GMCs, expressed in EL.U/mL.

Secondary Outcome Measures

1. Number of Seropositive Subjects for Anti-HPV-16 Antibodies at Day 1 in HPV-093 (NCT03355820) and at Year 6 in HPV-039 (NCT00779766) Studies [At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study) and at Year 6 in HPV-039 (NCT00779766) study]

   A seropositive subject is defined as a subject whose antibody concentration is equal to or above the cut-off value of 19 EL.U/mL. The number of seropositive subjects at Day 1 in the present study was compared with the number of seropositive subjects from the immunogenicity subset in HPV-039 (NCT00779766) study at Year 6. Data corresponding to Day 1 time point of the present study can also be found in the primary outcome measure. Data at Year 6 in subjects from the immunogenicity subset in HPV-039 study can be found in the respective NCT record NCT00779766 (please refer to Outcome measure 38, Row "≥19 EL.U/mL, sero-, [Month 72]" and Row "≥19 EL.U/mL, sero+, [Month 72]").

2. Number of Seropositive Subjects for Anti-HPV-18 Antibodies at Day 1 in HPV-093 (NCT03355820) and at Year 6 in HPV-039 (NCT00779766) Studies [At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study) and at Year 6 in HPV-039 (NCT00779766) study]

   A seropositive subject is defined as a subject whose antibody concentration is equal to or above the cut-off value of 18 EL.U/mL. The number of seropositive subjects at Day 1 in the present study was compared with the number of seropositive subjects from the immunogenicity subset in HPV-039 (NCT00779766) study at Year 6. Data corresponding to Day 1 time point of the present study can also be found in the primary outcome measure. Data at Year 6 in subjects from the immunogenicity subset in HPV-039 study can be found in the respective NCT record NCT00779766 (please refer to Outcome measure 39, Row "≥ 18 EL.U/mL, sero- [Month 72]" and Row "≥ 18 EL.U/mL, sero+ [Month 72]).

3. Concentration of Antibodies Against HPV-16 at Day 1 in HPV-093 (NCT03355820) and at Year 6 in HPV-039 (NCT00779766) Studies [At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study) and at Year 6 in HPV-039 (NCT00779766) study]

   Anti-HPV-16 antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in EL.U/mL. Anti-HPV-16 antibody concentrations at Day 1 in the present study were compared with the anti-HPV-16 antibody concentrations obtained as per the analysis performed on the immunogenicity subset in HPV-039 (NCT00779766) study at Year 6. Data corresponding to Day 1 time point of the present study can also be found in the primary outcome measure. Data at Year 6 in subjects from the immunogenicity subset in HPV-039 study can be found in the respective NCT record NCT00779766 (please refer to Outcome measure 40, Row "HPV-16, sero-, [Month 72]" and Row "HPV-16, sero+, [Month 72]").

4. Concentration of Antibodies Against HPV-18 at Day 1 in HPV-093 (NCT03355820) and at Year 6 in HPV-039 (NCT00779766) Studies [At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study) and at Year 6 in HPV-039 (NCT00779766) study]

   Anti-HPV-18 antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in EL.U/mL. Anti-HPV-18 antibody concentrations at Day 1 in the present study were compared with the anti-HPV-18 antibody concentrations obtained as per the analysis performed on the immunogenicity subset in HPV-039 (NCT00779766) study at Year 6. Data corresponding to Day 1 time point of the present study can also be found in the primary outcome measure. Data at Year 6 in subjects from the immunogenicity subset in HPV-039 study can be found in the respective NCT record NCT00779766 (please refer to Outcome measure 40, Row "HPV-18, sero-, [Month 72]" and Row "HPV-18, sero+, [Month 72]").

Eligibility Criteria

Criteria

• Ages Eligible for Study: 17 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects/subject's parents/legally acceptable representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply with the requirements of the protocol.

• Written informed consent obtained from the subject or subject's parents/LAR(s) prior to performing any study specific procedure.

• Written informed assent obtained from the subjects below the legal age of consent.

• Subjects who received all three doses of the HPV-16/18 vaccine in the HPV-058 study.

• Healthy subjects as established by medical history and clinical examination before entering into the study.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine which may have an impact on the study objectives) during the period starting 30 days (Day 29 to Day

1. before the study visit.

• Concurrently participating in another clinical study, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).

• Previous vaccination against HPV outside the HPV-058 study.

• Subjects with contraindications related to blood draw such as blood disorders and anticoagulants use.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Taizhou	Jiangsu	China	225300

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - May 19, 2017
• Statistical Analysis Plan - Mar 21, 2018

More Information

Publications

• Hu Y, Zhang X, He Y, Ma Z, Xie Y, Lu X, Xu Y, Zhang Y, Jiang Y, Xiao H, Struyf F, Folschweiller N, Jiang J, Poncelet S, Karkada N, Jastorff A, Borys D. Long-term persistence of immune response to the AS04-adjuvanted HPV-16/18 vaccine in Chinese girls aged 9-17 years: Results from an 8-9-year follow-up phase III open-label study. Asia Pac J Clin Oncol. 2020 Dec;16(6):392-399. doi: 10.1111/ajco.13398. Epub 2020 Aug 11.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03355820
• Other Study ID Numbers: 207347; 2017-000255-50
• First Posted: Nov 28, 2017
• Last Update Posted: Nov 19, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: Immune response; Cervarix; Persistence; Chinese; Human papillomavirus
• Additional relevant MeSH terms: Cervical Intraepithelial Neoplasia; Antibodies

Study Results

Participant Flow

Recruitment Details	This study was conducted at a single center in China.
Pre-assignment Detail	228 subjects were included in the Enrolled Set, 1 subject was excluded from all statistical analyses, thus 227 subjects formed the Exposed Set.

Arm/Group Title	HPV Group
Arm/Group Description	Healthy Chinese female subjects, including and above 17 years of age at the time of enrollment, who received all three doses of the Cervarix vaccine in the HPV-058 (NCT00996125) primary study.
Period Title: Overall Study
STARTED	227
COMPLETED	227
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	HPV Group
Arm/Group Description	Healthy Chinese female subjects, including and above 17 years of age at the time of enrollment, who received all three doses of the Cervarix vaccine in the HPV-058 (NCT00996125) primary study.
Overall Participants	227
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	21.6 (2.3)
Sex: Female, Male (Count of Participants)
Female	227 100%
Male	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian - East Asian Heritage	227 100%

Outcome Measures

1. Primary Outcome

Title	Number of Seropositive Subjects for Anti-HPV-16 Antibodies at Day 1 in HPV-093 (NCT03355820) Study
Description	A seropositive subject is defined as a subject whose antibody concentration is equal to or above the cut-off value of 19 Enzyme Linked Immunosorbent Assay units per milliliter (EL.U/mL).
Time Frame	At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Per-Protocol Set (PPS) for analysis of immunogenicity, which included all evaluable subjects who were included in the according to protocol (ATP) immunogenicity analysis of the primary vaccination study HPV-058 (NCT00996125), and with serology results available at this blood sampling time point.

Arm/Group Title	HPV Group
Arm/Group Description	Healthy Chinese female subjects, including and above 17 years of age at the time of enrollment, who received all three doses of the Cervarix vaccine in the HPV-058 (NCT00996125) primary study.
Measure Participants	223
Count of Participants [Participants]	223 98.2%

2. Primary Outcome

Title	Number of Seropositive Subjects for Anti-HPV-18 Antibodies at Day 1 in HPV-093 (NCT03355820) Study
Description	A seropositive subject is defined as a subject whose antibody concentration is equal to or above the cut-off value of 18 EL.U/mL.
Time Frame	At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Per-Protocol Set (PPS) for analysis of immunogenicity, which included all evaluable subjects who were included in the according to protocol (ATP) immunogenicity analysis of the primary vaccination study HPV-058 (NCT00996125), and with serology results available at this blood sampling time point.

Arm/Group Title	HPV Group
Arm/Group Description	Healthy Chinese female subjects, including and above 17 years of age at the time of enrollment, who received all three doses of the Cervarix vaccine in the HPV-058 (NCT00996125) primary study.
Measure Participants	223
Count of Participants [Participants]	223 98.2%

3. Primary Outcome

Title	Anti-HPV-16 Antibody Concentrations at Day 1 in HPV-093 (NCT03355820) Study
Description	Anti-HPV-16 antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in EL.U/mL.
Time Frame	At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Per-Protocol Set (PPS) for analysis of immunogenicity, which included all evaluable subjects who were included in the according to protocol (ATP) immunogenicity analysis of the primary vaccination study HPV-058 (NCT00996125), and with serology results available at this blood sampling time point.

Arm/Group Title	HPV Group
Arm/Group Description	Healthy Chinese female subjects, including and above 17 years of age at the time of enrollment, who received all three doses of the Cervarix vaccine in the HPV-058 (NCT00996125) primary study.
Measure Participants	223
Geometric Mean (95% Confidence Interval) [EL.U/mL]	1236.3

4. Primary Outcome

Title	Anti-HPV-18 Antibody Concentrations at Day 1 in HPV-093 (NCT03355820) Study
Description	Anti-HPV-18 antibody concentrations are presented as GMCs, expressed in EL.U/mL.
Time Frame	At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Per-Protocol Set (PPS) for analysis of immunogenicity, which included all evaluable subjects who were included in the according to protocol (ATP) immunogenicity analysis of the primary vaccination study HPV-058 (NCT00996125), and with serology results available at this blood sampling time point.

Arm/Group Title	HPV Group
Arm/Group Description	Healthy Chinese female subjects, including and above 17 years of age at the time of enrollment, who received all three doses of the Cervarix vaccine in the HPV-058 (NCT00996125) primary study.
Measure Participants	223
Geometric Mean (95% Confidence Interval) [EL.U/mL]	535.6

5. Secondary Outcome

Title	Number of Seropositive Subjects for Anti-HPV-16 Antibodies at Day 1 in HPV-093 (NCT03355820) and at Year 6 in HPV-039 (NCT00779766) Studies
Description	A seropositive subject is defined as a subject whose antibody concentration is equal to or above the cut-off value of 19 EL.U/mL. The number of seropositive subjects at Day 1 in the present study was compared with the number of seropositive subjects from the immunogenicity subset in HPV-039 (NCT00779766) study at Year 6. Data corresponding to Day 1 time point of the present study can also be found in the primary outcome measure. Data at Year 6 in subjects from the immunogenicity subset in HPV-039 study can be found in the respective NCT record NCT00779766 (please refer to Outcome measure 38, Row "≥19 EL.U/mL, sero-, [Month 72]" and Row "≥19 EL.U/mL, sero+, [Month 72]").
Time Frame	At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study) and at Year 6 in HPV-039 (NCT00779766) study

Outcome Measure Data

Analysis Population Description

The analysis was performed on the PPS for analysis of immunogenicity in HPV-093 study and on the ATP cohort for analysis of immunogenicity which included all evaluable subjects in the immunogenicity subset of HPV-039 study. For Year 6 data in HPV-039 study, please refer to the Outcome measure 38 in NCT00779766 record.

Arm/Group Title	HPV Group
Arm/Group Description	Healthy Chinese female subjects, including and above 17 years of age at the time of enrollment, who received all three doses of the Cervarix vaccine in the HPV-058 (NCT00996125) primary study.
Measure Participants	223
Count of Participants [Participants]	223 98.2%

6. Secondary Outcome

Title	Number of Seropositive Subjects for Anti-HPV-18 Antibodies at Day 1 in HPV-093 (NCT03355820) and at Year 6 in HPV-039 (NCT00779766) Studies
Description	A seropositive subject is defined as a subject whose antibody concentration is equal to or above the cut-off value of 18 EL.U/mL. The number of seropositive subjects at Day 1 in the present study was compared with the number of seropositive subjects from the immunogenicity subset in HPV-039 (NCT00779766) study at Year 6. Data corresponding to Day 1 time point of the present study can also be found in the primary outcome measure. Data at Year 6 in subjects from the immunogenicity subset in HPV-039 study can be found in the respective NCT record NCT00779766 (please refer to Outcome measure 39, Row "≥ 18 EL.U/mL, sero- [Month 72]" and Row "≥ 18 EL.U/mL, sero+ [Month 72]).
Time Frame	At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study) and at Year 6 in HPV-039 (NCT00779766) study

Outcome Measure Data

Analysis Population Description

The analysis was performed on the PPS for analysis of immunogenicity in HPV-093 study and on the ATP cohort for analysis of immunogenicity which included all evaluable subjects in the immunogenicity subset of HPV-039 study. For Year 6 data in HPV-039 study, please refer to the Outcome measure 39 in NCT00779766 record.

Arm/Group Title	HPV Group
Arm/Group Description	Healthy Chinese female subjects, including and above 17 years of age at the time of enrollment, who received all three doses of the Cervarix vaccine in the HPV-058 (NCT00996125) primary study.
Measure Participants	223
Count of Participants [Participants]	223 98.2%

7. Secondary Outcome

Title	Concentration of Antibodies Against HPV-16 at Day 1 in HPV-093 (NCT03355820) and at Year 6 in HPV-039 (NCT00779766) Studies
Description	Anti-HPV-16 antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in EL.U/mL. Anti-HPV-16 antibody concentrations at Day 1 in the present study were compared with the anti-HPV-16 antibody concentrations obtained as per the analysis performed on the immunogenicity subset in HPV-039 (NCT00779766) study at Year 6. Data corresponding to Day 1 time point of the present study can also be found in the primary outcome measure. Data at Year 6 in subjects from the immunogenicity subset in HPV-039 study can be found in the respective NCT record NCT00779766 (please refer to Outcome measure 40, Row "HPV-16, sero-, [Month 72]" and Row "HPV-16, sero+, [Month 72]").
Time Frame	At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study) and at Year 6 in HPV-039 (NCT00779766) study

Outcome Measure Data

Analysis Population Description

The analysis was performed on the PPS for analysis of immunogenicity in HPV-093 study and on the ATP cohort for analysis of immunogenicity which included all evaluable subjects in the immunogenicity subset of HPV-039 study. For Year 6 data in HPV-039 study, please refer to the Outcome measure 40 in NCT00779766 record.

Arm/Group Title	HPV Group
Arm/Group Description	Healthy Chinese female subjects, including and above 17 years of age at the time of enrollment, who received all three doses of the Cervarix vaccine in the HPV-058 (NCT00996125) primary study.
Measure Participants	223
Geometric Mean (95% Confidence Interval) [EL.U/mL]	1236.3

8. Secondary Outcome

Title	Concentration of Antibodies Against HPV-18 at Day 1 in HPV-093 (NCT03355820) and at Year 6 in HPV-039 (NCT00779766) Studies
Description	Anti-HPV-18 antibody concentrations are presented as Geometric Mean Concentrations (GMCs), expressed in EL.U/mL. Anti-HPV-18 antibody concentrations at Day 1 in the present study were compared with the anti-HPV-18 antibody concentrations obtained as per the analysis performed on the immunogenicity subset in HPV-039 (NCT00779766) study at Year 6. Data corresponding to Day 1 time point of the present study can also be found in the primary outcome measure. Data at Year 6 in subjects from the immunogenicity subset in HPV-039 study can be found in the respective NCT record NCT00779766 (please refer to Outcome measure 40, Row "HPV-18, sero-, [Month 72]" and Row "HPV-18, sero+, [Month 72]").
Time Frame	At Day 1 in HPV-093 (NCT03355820) study (i.e. 7 to 8 years after completion of the vaccination schedule in HPV-058 [NCT00996125] study) and at Year 6 in HPV-039 (NCT00779766) study

Outcome Measure Data

Analysis Population Description

The analysis was performed on the PPS for analysis of immunogenicity in HPV-093 study and on the ATP cohort for analysis of immunogenicity which included all evaluable subjects in the immunogenicity subset of HPV-039 study. For Year 6 data in HPV-039 study, please refer to the Outcome measure 40 in NCT00779766 record.

Arm/Group Title	HPV Group
Arm/Group Description	Healthy Chinese female subjects, including and above 17 years of age at the time of enrollment, who received all three doses of the Cervarix vaccine in the HPV-058 (NCT00996125) primary study.
Measure Participants	223
Geometric Mean (95% Confidence Interval) [EL.U/mL]	535.6

Adverse Events

Time Frame	At Day 1
Adverse Event Reporting Description	There were no adverse events (AEs) data collected during the entire study period (i.e. at Day 1). Only SAEs related to study procedures or concomitant GSK medications/vaccines and events with a fatal outcome were recorded and collected during the entire study period (i.e. at Day 1).
Arm/Group Title	HPV Group
Arm/Group Description	Healthy Chinese female subjects, including and above 17 years of age at the time of enrollment, who received all three doses of the Cervarix vaccine in the HPV-058 (NCT00996125) primary study.
All Cause Mortality
	HPV Group
	Affected / at Risk (%)	# Events
Total	0/227 (0%)
Serious Adverse Events
	HPV Group
	Affected / at Risk (%)	# Events
Total	0/227 (0%)
Other (Not Including Serious) Adverse Events
	HPV Group
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.