Evaluation of Safety and Immunogenicity of Co-administering Human Papillomavirus (HPV) Vaccine With Other Vaccines in Healthy Female Subjects

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Infections, Papillomavirus

Treatments: Biological: GSK Biologicals' HPV-16/18 L1 AS04 vaccine (Cervarix TM); Biological: Boostrix ® Polio

Study type: Interventional

Funder types: Industry

Identifiers

NCT00426361

108464

Details and patient eligibility

About

Infection with human papillomavirus (HPV) has been clearly established as the central cause of cervical cancer. Vaccination of pre-teens and adolescents, ideally before sexual debut and thus before exposure to oncogenic HPV, is a rational strategy for prevention of cervical cancer, and so HPV vaccination could complement the existing pre-adolescent/adolescents platform. Therefore, this Phase IIIb study is designed to evaluate the safety and immunogenicity of co-administering Boostrix polio (dTpa-IPV) with GSK Biologicals' (580299)HPV-16/18 L1 AS04 vaccine (Cervarix TM) as compared to the administration of either vaccine alone.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Enrollment: 751 patients

Sex: Female

Ages: 10 to 18 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Subjects who the investigator believes that they and their parents/legally acceptable representatives can, and will, comply with the requirements of the protocol should be enrolled in the study.
• A female between, and including, 10 and 18 years of age at the time of the first vaccination.
• Written informed consent/assent obtained from the subject prior to enrolment. For subjects above the legal age of consent, written informed consent must be obtained from the subject. For subjects below legal age of consent, written informed consent obtained from the subject's parent/LAR, and written informed assent must be obtained from the subject.
• Healthy subjects, as established by medical history and history-directed physical examination, before entering into the study.
• Previously completed routine childhood vaccinations according to the recommended vaccination schedule at the time.
• Subjects must have a negative urine pregnancy test.
• Subject 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 must agree to continue such precautions for two months after completion of the vaccination series. Subjects who reach menarche during the study, and therefore become of childbearing potential, must agree to follow the same precautions.

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 (up to Month 12/13).
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device).
• 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(s). Administration of routine vaccines up to 8 days before the first dose of study vaccine is allowed. Enrolment will be deferred until the subject is outside of specified window.
• A woman planning to become pregnant, likely to become pregnant 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
• Administration of a diphtheria, tetanus, pertussis (DTP) vaccine, diphtheria-tetanus (Td) booster or dTpa vaccine within the previous five years.
• Administration of a pre-school booster of Oral Polio Vaccine (OPV) or Inactivated Polio Virus (IPV) vaccine (4 or 5th dose) within the previous five years.
• Hypersensitivity to latex.
• Known acute or chronic, clinically significant neurologic, hepatic or renal functional abnormality or thrombocytopenia, 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.
• History of encephalopathy within seven days of administration of a previous dose of pertussis vaccine that is not attributable to another identifiable cause.
• Temperature of >=40°C within 48 hours of receipt of a prior dose of DTP vaccine (DTPw and/or DTPa), not due to another identifiable cause.
• Collapse or shock-like state within 48 hours of receipt of a prior dose of DTP vaccine (DTPw and/or DTPa).
• Seizures with or without fever within three days of a prior dose of DTP vaccine (Diphtheria, Tetanus, whole cell Pertussis vaccine DTPw and/or Diphtheria, Tetanus, acellular Pertussis vaccine DTPa).
• Persistent, inconsolable crying lasting >=3 hours, occurring within 48 hours of a prior dose of DTP vaccine (DTPw and/or DTPa).
• Severe Arthus-type hypersensitivity reactions following a prior dose of tetanus toxoid within the previous 10 years.
• Known exposure to diphtheria or household exposure to pertussis within 30 days before (i.e., Day 0-29) vaccination with Diphtheria, Tetanus, acellular Pertussis and inactivated polio virus vaccine (dTpa-IPV).
• Diphtheria and/or tetanus and/or pertussis and/or polio diagnosed within 30 days before (i.e., Day 0-29) vaccination with dTpa-IPV.
• Presence of a contra-indication to vaccination according to the product leaflet of the commercially available dTpa-IPV vaccine.
• 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 3 months preceding the first dose of study vaccine or planned administration during the study period. Enrolment will be postponed until the subject is outside the specified window.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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751 participants in 3 patient groups

Cervarix Group

Experimental group

Description:

Subjects who received GSK Biologicals' HPV-16/18 L1 AS04 vaccine (Cervarix TM) at Month 0, 1 and 6.

Treatment:

Biological: GSK Biologicals' HPV-16/18 L1 AS04 vaccine (Cervarix TM)

Boostrix Polio → Cervarix Group

Experimental group

Description:

Subjects who received Boostrix™ Polio at Month 0 and GSK Biologicals' HPV-16/18 L1 AS04 vaccine (Cervarix TM) at Month 1, 2 and 7.

Treatment:

Biological: GSK Biologicals' HPV-16/18 L1 AS04 vaccine (Cervarix TM)

Biological: Boostrix ® Polio

Cervarix + Boostrix Polio Group

Experimental group

Description:

Subjects who received GSK Biologicals' HPV-16/18 L1 AS04 vaccine (Cervarix TM) at Month 0, 1 and 6 with co-administration of Boostrix™ Polio at Month 0.

Treatment:

Biological: GSK Biologicals' HPV-16/18 L1 AS04 vaccine (Cervarix TM)

Biological: Boostrix ® Polio