Partially Blind Study to Evaluate Immunogenicity & Safety of GSK Bio's HPV Vaccine 580299 in Healthy Women Aged 9-25 Yrs

Phase 1CompletedNCT00541970

GlaxoSmithKline961 enrolled

Overview

Human Papillomavirus (HPV) infection has been established as a necessary cause of cervical cancer. GlaxoSmithKline (GSK) Biologicals has developed an HPV vaccine (580299) which targets the 2 most common oncogenic HPV types (HPV-16 and HPV-18), found in approximately 70% of all cervical cancers. In previous trials this vaccine has been found to be efficacious in the prevention of incident and persistent HPV-16/18 infections and associated cytological abnormalities and cervical dysplasia. In this partially-blind study, GSK Biologicals will evaluate the safety and immunogenicity of the HPV vaccine using an alternative schedule and an alternative dosing when administered in healthy young females aged 9 to 25 years, as compared to the standard HPV vaccine. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. The protocol posting has been updated following a protocol amendment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Enrollment

961

Conditions

Infections, Papillomavirus

Interventions

Eligibility

Sex: FEMALEMin age: 9 YearsMax age: 25 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Subjects who the investigator believes that they and/or their parents can and will comply with the requirements of the protocol should be enrolled in the study. * A female subject between, and including, 9 and 25 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 the legal age of consent, written informed consent from the subject's parents/legally acceptable representative, and written informed assent must be obtained from the subject. * Healthy subjects as established by medical history and history-oriented clinical examination before entering into the study. * 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 continue such precautions for two months after completion of the vaccination series. Exclusion Criteria: * Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period (up to Month 24). * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. * Concurrently participating in another clinical study, at any time during the study period (up to Month 24), in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). * Planned administration/administration of a vaccine not foreseen by the study protocol within 30 days before and 30 days after the first dose of vaccine. Planned administration/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. * Pregnant or breastfeeding female. * A woman planning to become pregnant or planning to discontinue contraceptive precautions during the study period, up to two months after the last vaccine dose. * Previous vaccination against HPV or planned administration of any HPV vaccine other than that foreseen by the study protocol during the study period (up to Month 24). * Previous administration of components of the investigational vaccine. * Cancer or autoimmune disease under treatment. * Any medically diagnosed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. * Hypersensitivity to latex. * Acute disease at the time of enrolment. * Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests. * 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 (up to Month 24).

Locations (25)

GSK Investigational Site

Edmonton, Alberta, Canada

GSK Investigational Site

Langley, British Columbia, Canada

GSK Investigational Site

St. John's, Newfoundland and Labrador, Canada

GSK Investigational Site

Truro, Nova Scotia, Canada

GSK Investigational Site

Québec, Quebec, Canada

GSK Investigational Site

Karlsruhe, Baden-Wurttemberg, Germany

GSK Investigational Site

Kehl, Baden-Wurttemberg, Germany

GSK Investigational Site

Rheinstetten, Baden-Wurttemberg, Germany

GSK Investigational Site

Tauberbischofsheim, Baden-Wurttemberg, Germany

GSK Investigational Site

Munich, Bavaria, Germany

...and 15 more locations

Outcomes

Primary Outcomes

Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies

Titers are given as Geometric Mean Titers (GMTs) expressed in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

Time frame: One month after vaccination with the last dose of the Cervarix vaccine (Cervarix 1/Placebo Group: Month 3; Other groups: Month 7).

Number of Subjects With Report of Any, and Grade 3 Solicited Local Symptoms

Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the solicited local symptom irrespective of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling larger than (\>) 50 millimeters (mm).

Time frame: Within 7 days (Day 0-6) after 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 or above (≥) 37.5 degrees Celsius (°C), gastrointestinal symptoms, which included nausea, vomiting, diarrhoea and/or abdominal pain, headache, myalgia, rash and urticaria. Grade 3 symptoms = symptoms that prevented normal activity. Grade 3 fever = axillary temperature ≥ 39 °C. Grade 3 urticaria = urticaria distributed on at least 4 body areas. Related symptom = symptom assessed by the investigator to be causally related to vaccination.

Time frame: Within 7 days (Day 0-6) after vaccination.

Secondary Outcomes

Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies .

Titers are given as Geometric Mean Titers (GMTs) expressed in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). The analysis was performed on the subjects who were administered a 2-dose vaccination schedule.

Time frame: At Month 3, 1 month after the second dose of vaccine or placebo

Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies

Titers are given as Geometric Mean Titers (GMTs) expressed in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). Groups were stratified into 3 age strata: 9-14, 15-19 and 20-25 years of age at the time of first vaccination. The 15-19 years age stratum in the group receiving the Cervarix vaccine on a 3-dose vaccination schedule was considered an active comparator.

Time frame: At Month 7, 1 month after the last dose of vaccine or placebo.

Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies

Titers are given as Geometric Mean Titers (GMTs) expressed in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

Time frame: At Month 12, at Month 18, at Month 24, at Month 36, and at Month 48 during the safety follow-up phase.

Titers of Anti-Papillomavirus 16 (Anti-HPV-16) and Anti-human Papillomavirus 18 (Anti-HPV-18) Antibodies

Titers are given as Geometric Mean Titers (GMTs) expressed in Enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).

Time frame: At Month 7, 1 month after the last dose of vaccine or placebo.