Immunogenicity and Safety of a Commercially Available Vaccine Co-administered With GSK HPV Vaccine (580299)

Evaluation of the Immunogenicity and Safety of a Commercially Available Vaccine When Co-administered With GlaxoSmithKline Biologicals' HPV Vaccine (580299) in Healthy Female Subjects.

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00637195

Enrollment

152

Registered

2008-03-17

Start date

2008-03-11

Completion date

2009-06-18

Last updated

2020-01-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Infections, Papillomavirus, Papillomavirus Vaccines

Keywords

Human papillomavirus (HPV) vaccine, Hepatitis B, Cervical cancer, HPV, Papillomavirus

Brief summary

Infection with human papillomavirus (HPV) has been clearly established as the necessary cause of cervical cancer. The current Phase 3b study is designed to assess the immunogenicity and safety of a commercially available vaccine co-administered with GlaxoSmithKline Biologicals' HPV vaccine GSK580299 in healthy female subjects.

Interventions

BIOLOGICALSubjects received 3 doses of GSK Biologicals' HPV vaccine (580299) (Cervarix™)

Intramuscular administration, 3 doses.

BIOLOGICALEngerix™

Intramuscular administration, 4 doses.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

20 Years to 25 Years

Healthy volunteers

Yes

Inclusion criteria

* Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study. * A female between, and including, 20 and 25 years of age at the time of the first vaccination. * Written informed consent obtained from the subject. * Healthy subjects as established by medical history and history directed clinical examination before entering into the study. * Subjects must not be pregnant. * Subjects must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.

Exclusion criteria

* Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. * Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. * Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after each dose of vaccine. Administration of routine vaccines such as meningococcal, inactivated influenza, diphtheria/tetanus and/or diphtheria/tetanus-containing vaccines up to 8 days before the first dose of study vaccine is allowed. * Concurrently participating in another clinical study, at any time during the study period (up to Month 13), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). * A subject planning to become pregnant, likely to become pregnant (as determined by the investigator) or planning to discontinue contraceptive precautions during the study period and up to two months after the last vaccine dose. * Pregnant or breastfeeding women. * Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period * Previous administration of components of the investigational vaccine. * Previous vaccination against hepatitis B or planned administration of any hepatitis B vaccine other than that foreseen by the study protocol during the study period. * History of hepatitis B infection. * Known exposure to hepatitis B within the previous 6 weeks. * Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality, as determined by previous physical examination or laboratory tests. * Cancer or autoimmune disease under treatment. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination * Acute disease at the time of enrolment. * Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

Design outcomes

Primary

Measure	Time frame	Description
Number of Subjects Seroprotected Against Hepatitis B Following 3 Doses of Engerix	Month 3	A subject seroprotected against hepatitis B is a subject with anti-hepatitis B surface antigen (HBs) antibody titers greater than or equal to 10 milli-international units per milliliter (mIU/mL).
Anti-hepatitis B Surface Antigen (HBs) Antibody Titers Following 3 Doses of Engerix	Month 3	Titers are given as Geometric Mean Titers (GMTs) expressed as milli-international units per milliliter (mIU/mL).

Secondary

Measure	Time frame	Description
Number of Subjects Seroconverted for Anti-hepatitis B (HBs) Antibodies	Months 2, 3 and 13	Anti-HBs seroconversion is defined as the appearance \[i.e. titer greater than or equal to the cut-off value of 3.3 milli-international units/milliliter (mIU/mL)\] of anti-HBs antibodies in the sera of subjects seronegative (with titers below the cut-off value) before vaccination.
Number of Subjects Seroprotected Against Anti-Hepatitis B (HBs) Antibodies Following 2 Doses of Engerix and After Completing the 4-dose Engerix Vaccination Course	Months 2 and 13	A subject seroprotected against Hepatitis B is a subject with anti-HBs antibody titers greater than or equal to 10 mIU/mL.
Anti-HBs Antibody Titers Following 2 Doses of Engerix and After Completing the 4-dose Engerix Vaccination Course	At Months 2 and 13	Titers are given as Geometric Mean Titers (GMTs) expressed as mIU/mL.
Number of Subjects Reporting Solicited Local Symptoms	During the 7-day period following any vaccination	Solicited local symptoms assessed include injection site pain, redness and swelling. Data are presented across doses.
Number of Subjects Seroconverted for Anti-human Papilloma Virus 16 and 18 (Anti-HPV-16 and Anti-HPV-18) Antibodies	Months 2 and 7	Seroconversion is defined as the appearance of antibodies with titers greater than or equal to the predefined cut-off value in the serum of subject seronegative before vaccination. Cut-off values assessed include 8 enzyme-linked immunosorbent assay units per milliliter (EL.U/mL) for anti-HPV-16 antibodies and 7 EL.U/mL for anti-HPV-18 antibodies.
Number of Subjects Reporting Unsolicited Adverse Events	During the 30-day period following any vaccination	Unsolicited adverse event covers any adverse event 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.
Number of Subjects Reporting Serious Adverse Events (SAE)	Up to study end (Month 13)	SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
Number of Subjects Reporting Medically Significant Conditions	Up to study end (Month 13)	Medically significant conditions include adverse events (AEs) 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.
Number of Subjects Reporting Solicited General Symptoms	During the 7-day period following any vaccination	Solicited general symptoms assessed include arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, temperature \[axillary route, ≥ 37.5 degree Celsius (°C)\] and urticaria. Data are presented across doses.
Anti-HPV-16/18 Antibody Titers	Months 2 and 7	Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).

Countries

Belgium

Participant flow

Participants by arm

Arm	Count
Cervarix™ & Engerix™ Group Subjects received 3 doses of GSK Biologicals' HPV vaccine (580299) (Cervarix™) (Months 0, 1 & 6) and 4 doses of Hepatitis B (Engerix™) vaccine (Months 0, 1, 2 & 12).	76
Engerix™ Group Subjects received 4 doses of Hepatitis B (HBV) vaccine (Months 0, 1, 2 & 12).	76
Total	152

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	1	0
Overall Study	Other	2	0
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Cervarix™ & Engerix™ Group	Engerix™ Group	Total
Age, Continuous	22.4 years STANDARD_DEVIATION 1.51	22.1 years STANDARD_DEVIATION 1.32	22.3 years STANDARD_DEVIATION 1.42
Sex: Female, Male Female	76 Participants	76 Participants	152 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	76 / 76	73 / 76
serious Total, serious adverse events	2 / 76	2 / 76

Outcome results

Primary

Anti-hepatitis B Surface Antigen (HBs) Antibody Titers Following 3 Doses of Engerix

Titers are given as Geometric Mean Titers (GMTs) expressed as milli-international units per milliliter (mIU/mL).

Time frame: Month 3

Population: Analysis was performed on the According-to-Protocol (ATP) cohort for analysis of immunogenicity, in subjects with available data and who were negative for anti-hepatitis B core antigen (anti-HBc) before vaccination.

Arm	Measure	Value (GEOMETRIC_MEAN)
Cervarix™ & Engerix™ Group	Anti-hepatitis B Surface Antigen (HBs) Antibody Titers Following 3 Doses of Engerix	156.1 mIU/mL
Engerix™ Group	Anti-hepatitis B Surface Antigen (HBs) Antibody Titers Following 3 Doses of Engerix	146.2 mIU/mL

Primary

Number of Subjects Seroprotected Against Hepatitis B Following 3 Doses of Engerix

A subject seroprotected against hepatitis B is a subject with anti-hepatitis B surface antigen (HBs) antibody titers greater than or equal to 10 milli-international units per milliliter (mIU/mL).

Time frame: Month 3

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cervarix™ & Engerix™ Group	Number of Subjects Seroprotected Against Hepatitis B Following 3 Doses of Engerix	70 Participants
Engerix™ Group	Number of Subjects Seroprotected Against Hepatitis B Following 3 Doses of Engerix	73 Participants

Secondary

Anti-HBs Antibody Titers Following 2 Doses of Engerix and After Completing the 4-dose Engerix Vaccination Course

Titers are given as Geometric Mean Titers (GMTs) expressed as mIU/mL.

Time frame: At Months 2 and 13

Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, in subjects with available data and who were negative for anti-hepatitis B core antigen (anti-HBc) before vaccination.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Cervarix™ & Engerix™ Group	Anti-HBs Antibody Titers Following 2 Doses of Engerix and After Completing the 4-dose Engerix Vaccination Course	Month 2	34.4 mIU/mL
Cervarix™ & Engerix™ Group	Anti-HBs Antibody Titers Following 2 Doses of Engerix and After Completing the 4-dose Engerix Vaccination Course	Month 13	19888.4 mIU/mL
Engerix™ Group	Anti-HBs Antibody Titers Following 2 Doses of Engerix and After Completing the 4-dose Engerix Vaccination Course	Month 2	35.7 mIU/mL
Engerix™ Group	Anti-HBs Antibody Titers Following 2 Doses of Engerix and After Completing the 4-dose Engerix Vaccination Course	Month 13	16927.5 mIU/mL

Secondary

Anti-HPV-16/18 Antibody Titers

Titers are given as Geometric Mean Titers (GMTs) expressed as Enzyme-linked Immunosorbent Assay Units Per Milliliter (EL.U/mL).

Time frame: Months 2 and 7

Population: Analysis was performed on the ATP cohort for analysis of immunogenicity, only for subjects receiving Cervarix™ vaccine with available data.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Cervarix™ & Engerix™ Group	Anti-HPV-16/18 Antibody Titers	Anti-HPV-16, Month 2	3497.2 EL.U/mL
Cervarix™ & Engerix™ Group	Anti-HPV-16/18 Antibody Titers	Anti-HPV-16, Month 7	8725.2 EL.U/mL
Cervarix™ & Engerix™ Group	Anti-HPV-16/18 Antibody Titers	Anti-HPV-18, Month 2	2775.6 EL.U/mL
Cervarix™ & Engerix™ Group	Anti-HPV-16/18 Antibody Titers	Anti-HPV-18, Month 7	4664.4 EL.U/mL

Secondary

Number of Subjects Reporting Medically Significant Conditions

Medically significant conditions include adverse events (AEs) 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.

Time frame: Up to study end (Month 13)